Novel anthranilic acid derivative or salt thereof


FIELD: chemistry.

SUBSTANCE: invention relates to novel anthranilic acid derivatives having inhibitory effect on production of matrix metalloprotease 13 of formula 1 , where R1 is a hydrogen atom or carboxy protective group selected from C1-3alkyl; R2 is phenyl, C3-6cycloalkyl, saturated or unsaturated 5-6-member heterocyclic group containing 1-3 heteroatoms selected from N, O, S, which can be condensed with phenyl, which can be optionally substituted with C1-6alkyl, C1-6alkoxy, acetyl, acetoxy, halogen, halogenC1-6alkyl, nitro group, hydroxyl group, CN, amino group, phenyl, saturated or unsaturated 5-6-member heterocyclic group containing 1-4 heteroatoms selected from N, O, S, which can be disubstituted with C1-6alkyl; R3 is phenyl, C3-6cycloalkyl, C5cycloalkenyl, saturated or unsaturated 5-6-member heterocyclic group containing 1-3 heteroatoms selected from N, O, S, which can be condensed with phenyl (except benzoxazole), which can be optionally substituted with C1-6alkyl, C1-6alkoxy, phenyl, acetyl, halogen, halogenC1-6alkyl, halogenC1-6alkoxy, nitro group, hydroxyl group, hydroxyC1-6alkyl, CN, acetylamino, ketone, phenoxy, benzoyl, benzyl, amino group, which can be disubstituted with C1-6alkyl, carboxy group, C1-6alkylsufonyl group or pyrrolyl; X1 is a carbonyl group or sulfonyl group; X2 is a C1-3alkylene, C2-3alkenylene or C2-3alkynylene group which can be optionally substituted with C1-3alkyl, or a bond; provided that when X1 is a sulfonyl group and X4 is a bond, X2 is a C1-3alkylene, C2-3alkenylene or C2-3alkynylene group which can be optionally substituted with C1-3alkyl; X3 is an oxygen atom or a bond; and X4 is a group with general formula -X5-X6- or -X6-X5-, where the bond on the left side of each formula is bonded to R3; and X5 is an oxygen atom, a sulphur atom, an imino group which can be optionally protected or a bond; X6 is a C1-4alkylene, C2-3alkenylene or C2-3alkynylene group or a bond, as well as to their pharmaceutically acceptable salts. The invention also relates to a matrix metalloprotease 13 production inhibitor and a therapeutic agent for making a medicinal agent for treating rheumatoid arthritis.

EFFECT: possibility of making a medicinal agent for treating rheumatoid arthritis.

8 cl, 7 tbl, 633 ex

 

The invention relates to a new derivative of Anthranilic acid or its salt, having the activity of inhibiting the production of metalloprotease 13 matrix (MMP-13).

The LEVEL of TECHNOLOGY

Metalloprotease matrix are a family consisting of zincability proteases, substrates which are components of the extracellular matrix and which are activated by cleavage of propeptide after secretion. More than 20 family members of metalloprotease matrix was identified in humans, and they are classified as collagenase (MMP-1, 8, 13), gelatinase (MMP-2, 9), stromelysin (MMP-3, 10), matrilysin (MMP-7, 26), membrane-type MMP (MMP-14, 15, 16, 17, 24, 25) according to the domain structure and substrate specificity. The overexpression of these metalloprotease matrix observed in various cancer cells, and it is believed that they are involved in their proliferation and metastasis. To date, developed anticancer agents which inhibit metalloprotease matrix (non-patent document 1).

Inhibitors metalloprotease matrix have been investigated as therapeutic agents for the treatment of rheumatoid arthritis and osteoarthritis. Articular cartilage is composed of collagen mesh cartilage type II, which are held proteoglycans of cartilage, such as aggrecan and hyaluronic acid. Metalloprotease full the CSA is involved in the maintenance of the extracellular matrix. When metalloprotease matrix and TIMP (tissue inhibitor of metalloprotease), their endogenous inhibitor, are not in equilibrium and the presence of metalloprotease matrix becomes excessive, can develop destruction of cartilage and bone. Especially when collagen fibers are damaged, and joints are subjected to progressive degradation that occurs in rheumatoid arthritis and osteoarthritis. Accordingly, suggest that long-term suppression of the development of the degradation of cartilage in rheumatoid arthritis and osteoarthritis can be enhanced by inhibition of excessive metalloprotease matrix (non-patent document 2).

When osteoarthritis also increases the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) α and extracellular matrix is destroyed. The production of metalloprotease matrix can be further enhanced by the products of destruction of collagen type II and fibronectin, leading to the development of the destruction of the matrix in cartilage. When such damage matrix exceeds a certain threshold value, the nature of the cartilage cells pathologically changed and destruction of the joint continues to evolve. MMP-13 plays a dominant role in the degradation of collagen type II (non-patent document 3).

Non-patent document 1: Current Oncology Reports, Vol. 6, page 96-102, 2004.

Non-patent document 2: Annals of the Rheumatic Diseases, Vol. 60, page 62-67, 2001.

Non-patent document 3: Biochemical Society Symposia, Vol. 70, page 115-123, 2003.

Description of the INVENTION

There is an urgent need for medicines inhibiting the production of metalloprotease matrix, especially MMP-13.

In such circumstances, the authors of the present invention have conducted extensive studies and consequently found that a derivative of Anthranilic acid represented by the General formula (1)

[Formula 1]

where R1represents a hydrogen atom or carboxyamide group; R2represents phenyl, cycloalkyl or heterocyclic group which may be optionally substituted; R3represents phenyl, cycloalkyl, cycloalkenyl, monocyclic heterocyclic or bicyclic heterocyclic group which may be optionally substituted; X1represents a carbonyl group or sulfonyloxy group; X2represents alkylenes, alkenylamine or alkynylamino group which may be optionally substituted or a bond; provided that when X1represents sulfonyloxy group and X4represents a bond, X2represents alkylenes, alkenylamine or alkynylamino group which may be optionally substituted; X3predstavljaet an oxygen atom, a sulfur atom or a bond; X4represents a group represented by the General formula-X5-X6or X6-X5-where the link on the left side of each General formula attached to R3; and X5represents an oxygen atom, a sulfur atom, aminogroup, which may be optionally protected, sulfinyl group or sulfonyloxy group or a bond; X6represents alkylenes, alkenylamine or alkynylamino group which may be optionally substituted, or Association, or its salt, has the activity of inhibiting the production of MMP-13 and, thus, created the present invention.

A new derivative of Anthranilic acid or its salt of the present invention has the activity of inhibiting the production of MMP-13 and, therefore, is suitable as, for example, a therapeutic agent for the treatment of rheumatoid arthritis, osteoarthritis, cancer and other diseases involving MMP-13.

The BEST WAY of carrying out the INVENTION

Below the connection of the present invention are described in detail.

In the present description, unless otherwise stated, a halogen atom refers to a fluorine atom, chlorine atom, bromine atom and iodine atom; the alkyl group includes, for example, linear or branched C1-12alkyl group such as methyl, ethyl, n the filing, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl and octyl; the lower alkyl group includes, for example, linear or branched C1-6alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl and isopentyl; Alchemilla group includes, for example, linear or branched C2-12alkenylphenol group, such as vinyl, allyl, propenyl, Isopropenyl, butenyl, Isobutanol, pentanol, hexanol, heptanol and octanol; Alchemilla group includes, for example, linear or branched C2-12alkenylphenol group, such as ethinyl, 2-PROPYNYL and 2-butynyl; cycloalkyl group includes, for example, With3-8cycloalkyl group, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; cycloalkenyl group includes, for example, With3-8cycloalkenyl group, such as cyclopropyl, cyclobutyl, cyclopentenyl and cyclohexenyl; Allenova group includes, for example, linear or branched C1-6alkalinous group, such as methylene, ethylene, propylene, butylene, hexylen; alkenylamine group includes, for example, linear or branched C2-6alkynylamino group, such as vinile, propylen, 2-butylen and 2-butylen; akinrinola group includes, for example, linear or RA is extensive With 2-6alkynylamino group such as ethynylene, propylen, 1-Butyrin and 2-Butylin; the aryl group includes, for example, such groups as phenyl and naphthyl; kalkilya group includes, for example, ar-C1-6alkyl group, such as benzyl, diphenylmethyl, trityl, phenethyl and naphthylmethyl; alkoxygroup includes, for example, linear or branched C1-6alkyloxy, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentane; alloctype includes, for example, a group like phenoxy, naphthoxy; alkoxyalkyl group includes, for example, With1-6alkyloxy-C1-6alkyl group, such as methoxymethyl and 1-ethoxyethyl; and aracelikarsaalyna group includes, for example, ar-C1-6alkyloxy-C1-6alkyl group, such as benzoyloxymethyl and penetrometer;

the acyl group includes, for example, formyl group, a linear or branched C2-12alkanoyloxy group, such as acetyl, propionyl and isovaleryl, ar-C1-6alkylcarboxylic group, such as benzylcarbamoyl, cyclic hydrocarbon carbonyl group such as benzoyl and naphtol, heterocyclic carbonyl group, such as nicotinoyl, thenoyl, pyrrolidinecarbonyl and furoyl, succinylcoa group, patriliny the group, mahailey group, falorni group and linear or branched α-aminoalcohol group formed from amino acids (examples of amino acids include glycine, alanine, valine, leucine, isoleucine, serine, threonine, cysteine, methionine, aspartic acid, glutamic acid, asparagine, glutamine, arginine, lysine, histidine, hydroxylysine, phenylalanine, tyrosine, tryptophan, Proline and hydroxyproline), whose N-terminal group may be optionally protected; allyloxycarbonyl group includes, for example, linear or branched C1-12allyloxycarbonyl group, such as methoxycarbonyl, etoxycarbonyl, 1,1-dimethylpropanolamine, isopropoxycarbonyl, 2-ethylhexyloxymethyl, tert-butoxycarbonyl and tert-pentyloxybenzoyl; aracelikarsaalyna group includes, for example, ar-C1-6allyloxycarbonyl group, such as benzyloxycarbonyl and ventilatsiooniga group; aryloxyalkyl group includes, for example, a group like vinyloxycarbonyl;

alloctype includes, for example, linear or branched C2-6alkanoyloxy, such as atomic charges, propionyloxy, and koilocyte, such as benzoyloxy; acidalkaline group includes, for example, a group like acetylethyl, benzoylmethyl, p-nitrobenzoyl, p-bromobenzo lmutil, p-methoxybenzoate and 1-benzoylethyl; aryloxyalkyl group includes, for example, a group like acetoxymethyl, propionylacetate and pivaloyloxymethyl; allylthiourea group includes, for example, With1-6alkylthio-C1-6alkyl group, such as methylthiomethyl, ethylthiomethyl and propylthiouracil; aristocrata includes, for example, a group like phenylthio; alkanesulfonyl group includes, for example, With1-6alkanesulfonyl group, such as methanesulfonyl, econsultancy and propanesulfonyl; arylsulfonyl group includes, for example, a group like benzazolyl, toluensulfonyl and naphthalenesulfonyl; alkanesulfonyl includes, for example, With1-6alkanesulfonyl, such as methanesulfonate, econsultancy; arylsulfonate includes, for example, a group like benzosulfimide, toluensulfonate; artioukhina group includes, for example, a group like phenylsulfanyl and 2-(p-nitrobenzylidene)ethyl; arylsulfonyl group includes, for example, a group like p-toluensulfonate; and alkanesulfonyl includes, for example, With1-6alkanesulfonyl, such as methanesulfonamido and econsultant.

Oxygen-containing heterocyclic group refers to, for example, chacoy group as 2-tetrahydropyranyl and 2-tetrahydrofuranyl; sulfur-containing heterocyclic group includes, for example, a group like tetrahydrothiopyran; heterocalixarenes group includes, for example, a group like 2-furfurylalcohol and 8-hinolincarbonova; nitrogen-containing heterocyclisation group includes, for example, a group like phthalimidomethyl and Succinimidyl; substituted silyl group includes, for example, such a group as trimethylsilyl, triethylsilyl and tributyrin; and alkylsalicylate group includes, for example, such groups as 2-(trimethylsilyl)ethyl.

Monocyclic heterocyclic group includes, for example, nitrogen-containing monocyclic heterocyclic group containing only the atom(s) of nitrogen as heteroatom(s)member(s) of the ring, such as pyrrolidine, pyrrolidinone, pyrrolidinyl, piperideine, piperazinilnom, imidazolidine, pyrazolidine, perederina, tetrahydropyridine, pyridinoline, piratininga, pyrimidinyl, tetrataenia, imidazolidinone, imidazolidinyl, piratininga and pyrazolidinone group; oxygen-containing monocyclic heterocyclic group containing only the atom(s) of oxygen as heteroatom(s)member(s) of the ring, such as furilla and Pernilla group; sulfur-containing monocyclic heterocyclic is the group containing only the atom(s) sulfur as heteroatom(s)member(s) of the ring, such as thienyl group; a nitrogen - and oxygen-containing monocyclic heterocyclic group containing only atoms of nitrogen and oxygen as heteroatoms member rings, such as oxazolidine, oxadiazolidine, isoxazolidine and morpholinyl group; nitrogen - and sulfur-containing monocyclic heterocyclic group containing only atoms of nitrogen and sulfur as heteroatoms member rings, such as thiazolidine, isothiazolinone, thiadiazolidine and thiomorpholine group; and the oxygen - and sulfur-containing monocyclic heterocyclic group containing only the atoms of oxygen and sulfur as heteroatoms member rings, such as tixanidine group.

Bicyclic heterocyclic group includes, for example, nitrogen-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only 1-3 nitrogen atom as the heteroatom of the specified ring, such as indayla, indolenine, 2-oxoindole, isoindoline, indolizinyl, benzimidazolyl, benzotriazolyl, indazolinone, kinolinna, tetrahydropyrimidine, tetrahydroisoquinoline, hyalinella, izochinolina, phthalazinone, naphthyridinone, Hinoki anilina, dihydroisoquinoline, chinadaily, indolenine, hinkleyville and 2,3-dihydrobenzofuranyl group; oxygen-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) of oxygen as heteroatom(s) specified ring, such as benzofuranyl, isobenzofuranyl, romanella, romanella, thrombilia, benzo-1,3-dioxolene, benzo-1,4-dioxinlika and 2,3-dihydrobenzofuranyl group; sulfur-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) sulfur as heteroatom(s) specified ring, such as benzothiazoline and 2,3-dihydrobenzofuranyl group; nitrogen - and oxygen-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) of nitrogen and oxygen as heteroatom(s) specified ring, such as benzoporphyrin and benzoporphyrin group; and the nitrogen - and sulfur-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) of nitrogen and sulfur as heteroatom(s) specified ring, such as benzothiazoline and benzothiadiazole group.

Heteros Klionsky group belongs, for example, a monocyclic heterocyclic group, a bicyclic heterocyclic group; tricyclic heterocyclic group, such as thianthrene, xantener, phenoxathiin, carbazolyl, β-carbolines, phenanthridines, acridines, pyrimidinyl, phenanthrolines, phenazines, phenothiazines and phenoxazines.

The cyclic amino group may be, for example, a saturated cyclic amino group and unsaturated amino group, it may optionally contain one or more heteroatoms, such as nitrogen atom, oxygen atom and sulfur atom and a carbon atom in the carbonyl in the ring and may be monocyclic, bicyclic or tricyclic; and more specifically it refers to saturated or unsaturated monocyclic 3-7-membered cyclic amino group having one nitrogen atom, such as aziridine-1-yl, azetidin-1-yl, pyrrolidin-1-yl, pyrrolin-1-yl, pyrrol-1-Il, dihydropyridines-1-yl, tetrahydropyridine-1-yl, piperidine-1-yl, dehydroacetic-1-yl and peligrosas-1-yl; a saturated or unsaturated monocyclic 3-7-membered cyclic amino group having 2 nitrogen atom, such as imidazol-1-yl, imidazolidin-1-yl, imidazolin-1-yl, pyrazolin-1-yl, piperazine-1-yl, 1,4-dihydropyridin-1-yl, 1,2-dihydropyrimidin-1-yl, permitability-1-silt and homopiperazin-1-yl; a saturated or unsaturated monocyclic 3-7-membered cyclica the coy amino group, having 3 or more nitrogen atoms, such as 1,2,4-triazole-1-yl, 1,2,3-triazole-1-yl, 1,2-dihydro-1,2,4-triazine-1-yl, perhydro-S-triazine-1-yl; a saturated or unsaturated monocyclic 3-7-membered cyclic amino group having 1-4 heteroatoms selected from oxygen atom and sulfur atom in addition to the atom(s) of nitrogen, such as oxazolidin-3-yl, isoxazolidine-2-yl, morpholine-4-yl, thiazolidin-3-yl thiazolidin-2-yl, thiomorpholine-4-yl, sometimesvalid-4-yl and 1,2,4-teziutlan-2-yl; a saturated or unsaturated bicyclic or tricyclic amino group, such as isoindoline-2-yl, indolin-1-yl, 1H-indazol-1-yl, 1H-indol-1-yl, 1H-benzimidazole-1-yl, purine-7-yl, tetrahydroquinolin-1-yl and tetrahydroisoquinoline-2-yl; a saturated or unsaturated 5-to 12-membered or spiritlessly bridged cyclic amino group such as 5-azaspiro[2.4]heptane-5-yl, 2,8-diazabicyclo[4.3.0]nonan-8-yl, 3-azabicyclo[3.1.0]hexane-3-yl, 2-oxa-5,8-diazabicyclo[4.3.0]nonan-8-yl, 2,8-diazaspiro[4.4]nonan-2-yl and 7-azabicyclo[2.2.1]heptane-7-yl.

Aminosidine group includes any group which can normally be used as a protective group of amino group, and examples include groups described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 494-615, 1999, John Wiley & Sons, INC. Specific examples include an acyl group, allyloxycarbonyl group, aracelikarsaalyna group, aryloxyalkyl the second group, aracelio group, alkoxyalkyl group, kalkylarksmall group, killigrew, alkanesulfonyl group, arylsulfonyl group and a substituted silyl group.

Aminosidine group includes any group which can normally be used as a protective group aminogroup, and examples include groups described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 494-615, 1999, John Wiley & Sons, INC. Specific examples include an acyl group, allyloxycarbonyl group, aracelikarsaalyna group, aryloxyalkyl group, aracelio group, alkoxyalkyl group, killigrew, alkanesulfonyl group, arylsulfonyl group and a substituted silyl group.

Hidroxizina group includes any group which can normally be used as a protective group of hydroxyl group, and examples include groups described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 17-245, 1999, John Wiley & Sons, INC. Specific examples include an acyl group, allyloxycarbonyl group, aracelikarsaalyna group, heterocalixarenes group, alkyl group, alkenylphenol group, aracelio group, oxygen-containing heterocyclic group, a sulfur-containing heterocyclic group, alkoxyalkyl group, kalkylarksmall group, alkanesulfonyl is the Rupp, arylsulfonyl group and a substituted silyl group.

Carboxyamide group includes any group which can normally be used as a protective group of carboxyl group, and examples include groups described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 369-453, 1999, John Wiley & Sons, INC. Specific examples include alkyl group, aryl group, aracelio group, arylalkyl group, alltoallw group, arylsulfonyl group, oxygen-containing heterocyclic group, alkylsulphonyl group, aryloxyalkyl group, nitrogen-containing heterocyclisation group, cycloalkyl group, alkoxyalkyl group, kalkylarksmall group, alkylthiomethyl group, alkenylphenol group and a substituted silyl group.

Phenolic hidroxizina group includes any group which can normally be used as a protective group of a phenolic hydroxyl group, and examples include groups described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 246-287, 1999, John Wiley & Sons, INC. Specific examples include an acyl group, alkyl group, alkenylphenol group, aracelio group, oxygen-containing heterocyclic group, a sulfur-containing heterocyclic group, alkoxyalkyl group, alkanesulfonyl group, arylsulfonyl group samewindow silyl group.

Toolsasthma group includes any group which can normally be used as a protective group Tilney group, and examples include groups described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 454-493, 1999, John Wiley & Sons, INC. Specific examples include an acyl group, alkyl group, alkenylphenol group, aracelio group, alkoxyalkyl group and a substituted silyl group.

Acetilcisteina group includes any group which can normally be used as a protective group of acetylene, and examples include groups described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 654-659, 1999, John Wiley & Sons, INC. Specific examples include substituted silyl group.

Examples of leaving groups include halogen atom, alkanolammonium, arylsulfonate and alloctype.

Salt compounds of General formula [1] includes commonly known salts formed the main group, such as amino group, or an acid group such as phenolic hydroxyl group or carboxyl group.

Examples of salts formed the basic group include salts of mineral acids such as hydrochloric acid, Hydrobromic acid and sulfuric acid; salts of organic carboxylic acids, such as tartaric acid, formic acid, acetic acid, citric sour is a, trichloroacetic acid and triperoxonane acid, and salts of sulfonic acid, such as methanesulfonate acid, benzolsulfonat acid, p-toluensulfonate acid, mesitylenesulfonic acid and naphthalenesulfonate acid.

Examples of salts formed by acidic group include salts of alkali metals such as sodium and potassium; salts of alkaline earth metals such as calcium and magnesium; ammonium salt and a salt of a group of nitrogen-containing organic bases such as trimethylamine, triethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, dicyclohexylamine, procaine, dibenzylamine, N-benzyl-β-phenethylamine and N,N'-dibenziletilendiaminom.

In addition, as the preferred salts of the compounds of General formula [1] includes pharmacologically acceptable salts.

Phenyl, cycloalkyl and heterocyclic groups, R2in the present invention can be optionally substituted by at least one group selected from a halogen atom, ceanography, nitro, acyl group, alloctype, sulfopropyl, phosphoryl group, alkanesulfonyl group, alkanesulfonyl, acetamidoxime, carbamoyl group, carboxyl, amino and hydroxyl groups which may be optionally protected with alkyl, alkenylphenol, alkinyl the th, alkoxy, aryl, cyclic amino, Uralkaliy and heterocyclic groups, which may be optionally substituted.

Phenyl, cycloalkyl, cycloalkenyl, monocyclic heterocyclic and bicyclic heterocyclic group in R3may be optionally substituted by at least one group selected from a halogen atom, ceanography, nitro, acyl group, alloctype, sulfopropyl, phosphoryl group, an amino group, alkanesulfonyl group, alkanesulfonyl, acetamidoxime, dimethylaminopropyl, carbamoyl group, carboxyl and hydroxyl groups, which can be optionally protected with alkyl, alkenylphenol, alkenylphenol, alkoxy, aryl, aryloxy, cyclic amino, Uralkaliy and heterocyclic groups, which may be optionally substituted.

Alkylene, alkenylamine and alkenylamine group in the X2and X6may be optionally substituted by at least one group selected from a halogen atom, ceanography, nitro, acyl group, sulfopropyl, phosphoryl group, alkanesulfonyl group, alkanesulfonyl, acetamidoxime, carbamoyl group, carboxyl, amino and hydroxyl groups which may be optionally protected with alkyl, alkenylphenol, alkinyl is Oh, alkoxy, aryl, cyclic amino, Uralkaliy and heterocyclic groups, which may be optionally substituted.

Examples of the substituent of the above alkyl, alkenylphenol, alkenylphenol, alkoxy, aryl, cyclic amino, Uralkaliy and heterocyclic groups, which may be optionally substituted, include halogen atom, a cyano, a nitro-group, acyl group, alphagroup, phosphoryl group, cyclic amino group, alkanesulfonyl group, alkanesulfonyl, acetaminoph, aracelio group, karbamoilnuyu group, alkyl group, alkenylphenol group, alkylamino group, alkoxygroup, aryl group, heterocyclic group and carboxyl, amino and hydroxyl groups which may be optionally protected.

Among the compounds of the present invention preferred compounds include the following compounds.

Compounds in which R1represents a hydrogen atom, are preferred.

Compounds in which R2represents phenyl,5-7cycloalkyl or heterocyclic group which may be optionally substituted, are preferred compounds in which R2represents phenyl or heterocyclic group which may be not necessarily Thames is on the group, selected from a halogen atom, ceanography, nitro, hydroxyl group which may be optionally protected, an alkyl group which may be optionally substituted, alkenylphenol group which may be optionally substituted, alkenylphenol group which may be optionally substituted, alkoxygroup, which may be optionally substituted, aryl group which may be optionally substituted, a cyclic amino group which may be optionally substituted, aranceles group which may be optionally substituted, and heterocyclic group which may be optionally substituted, are preferred compounds in which R2represents phenyl or heterocyclic group which may be optionally substituted by a group selected from a halogen atom, nitro group, hydroxyl group, alkyl group which may be optionally substituted, alkenylphenol group which may be optionally substituted, alkoxygroup, which may be optionally substituted, aryl group which may be optionally substituted, a cyclic amino group which may be optionally substituted, monocyclic heterocyclic group which may be optionally substituted, are even more preferred is entrusted, and compounds in which R2represents a phenyl group, oxygen-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) of oxygen as heteroatom(s) specified rings, sulfur-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) sulfur as heteroatom(s) specified ring, and the nitrogen - and sulfur-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) of nitrogen and sulfur as heteroatom(s) specified ring; and these groups may be optionally substituted by a group selected from a halogen atom, hydroxyl group, alkyl group which may be optionally substituted by a halogen atom, aryl group which may be optionally substituted by a halogen atom, a cyclic amino group and a nitrogen-containing monocyclic heterocyclic group containing only the atom(s) of nitrogen as heteroatom(s)member(s) of the ring are more preferred.

Compounds in which R3represents phenyl,5-7cycloalkyl,5-7cycloalkenyl or monocyclic heterocyclic or biciklizes the heterocyclic group, which may be optionally substituted, are preferred compounds in which R3represents phenyl, monocyclic heterocyclic or bicyclic heterocyclic group which may be optionally substituted by a group selected from a halogen atom, ceanography, nitro, acyl group, hydroxyl group, alkanesulfonyl groups, alkyl groups, which may be optionally substituted, alkoxygroup, which may be optionally substituted, aryl group which may be optionally substituted, alloctype, which may be optionally substituted, and heterocyclic group which may be optionally substituted, are preferred compounds in which R3represents phenyl, monocyclic heterocyclic or bicyclic heterocyclic group which may be optionally substituted by a group selected from a halogen atom, hydroxyl group, alkyl group which may be optionally substituted, and alkoxygroup, which may be optionally substituted, are even more preferred, and compounds in which R3represents a phenyl group, nitrogen-containing bicyclic heterocyclic group represented by a condensed or m is sicovam ring, only contains 1-3 nitrogen atom as heteroatom(s) specified ring, oxygen-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) of oxygen as heteroatom(s) specified ring, or the sulfur-containing bicyclic heterocyclic group represented by a condensed or bridged ring containing only the atom(s) sulfur as heteroatom(s) specified ring; and these groups may be optionally substituted by a group selected from a halogen atom, hydroxyl group, alkyl group which may be optionally substituted by a halogen atom, and alkoxygroup, which may be optionally substituted by a halogen atom are more preferable.

Compounds in which X1represents a carbonyl group, are preferred.

Compounds in which X2represents alkylenes, alkenylamine or alkynylamino group which may be optionally substituted by a group selected from alkyl and phenyl groups, which may be optionally substituted, or communication, are preferred compounds in which X2represents alkylenes, alkenylamine, alkynylamino group or Association, are more prepact the tion, and compounds in which X2represents alkylenes group, alkenylamine group or Association, are even more preferred.

Compounds in which X3represents an oxygen atom or bond are preferred, and compounds in which X3represents a bond are more preferable.

When X2represents alkylenes, alkenylamine or alkynylamino group which may be optionally substituted, the compounds in which X3represents an oxygen atom are preferred.

Compounds in which X4represents a group of General formula-X6-X5-where the link on the left side of the General formula attached to R3and X5represents an oxygen atom, a sulfur atom, aminogroup, which may be optionally protected, sulfonyloxy group, sulfonyloxy group or a bond; X6represents alkylenes, alkenylamine or alkynylamino group which may be optionally substituted, or communications are preferred.

Compounds in which X4represents a group of General formula-X6-X5P-where the link on the left side of the General formula attached to R3and X5Prepresents an oxygen atom, a sulfur atom, aminogroup and the and communication; and X6represents alkylenes, alkenylamine or alkynylamino group which may be optionally substituted, are preferred compounds in which X4represents a group of General formula-X6-X5q-where the link on the left side of the General formula attached to R3; and X5qrepresents an oxygen atom, a sulfur atom or a bond; X6has the same values as described above are more preferred, and compounds in which X4represents a group of General formula-X6q-X5r-where the link on the left side of the General formula attached to R3; and X5rrepresents a bond; and X6qrepresents alkylenes, alkenylamine or alkynylamino group are even more preferred. Compounds in which X4represents a group of General formula-X6r-X5p-where the link on the left side of the General formula attached to R3; and X6ris a bond and X5phas the values listed above are preferred, and compounds in which X4represents a group of General formula-X6r-X5s-where the link on the left side of the General formula attached to R3; and X5srepresents an oxygen atom or a bond; and X6rhas the values listed above are more preferred.

Examples of typical compounds among the compounds of the present invention include compounds of the following tables 1-6:

Table 1
R3R3
Phenyl2-Chlorophenyl
4-(tert-Butyl)phenyl3-Chlorophenyl
The thiazole-2-yl4-Chlorophenyl
Thiophene-2-yl3,5-Dichlorophenyl
Benzofuran-2-yl3,4-Dichlorophenyl
Benzofuran-5-yl2,3-Dichlorophenyl
1H-Benzimidazole-1-yl2,4-Dichlorophenyl
1H-Indol-1-yl2,5-Dichlorophenyl
1H-Indol-5-yl3-Chloro-2-forfinal
1H-Indol-4-yl5-Chloro-2-forfinal
4-(Methanesulfonyl)phenyl2-Chloro-6-forfei the
Benzothiophen-2-yl3-Chloro-4-forfinal
Benzothiophen-5-yl4-Hydroxyphenyl
3-Nitrophenyl3-Chloro-4-hydroxyphenyl
4-Nitrophenyl3-Cyanophenyl
4-Acetylphenyl4-Cyanophenyl
2-Forfinal2-were
3-Forfinal3-Were
4-Forfinal4-Were
2,3-Differenl2,3-Dimetilfenil
2,6-Differenl2,6-Dimetilfenil
3,4-Differenl3,4-Dimetilfenil
2.5-Differenl3, 5dimethylphenyl-4-hydroxyphenyl
3,5-Differenl3-Fluoro-4-were
2,4-Differenl4-fluoro-2-were
2-Methoxyphenyl3-Chloro-2-IU is ylphenyl
3-Methoxyphenyl3-Chloro-4-were
4-Methoxyphenyl3-Chloro-2-were
5-Chloro-2-methoxyphenyl2-Phenoxyphenyl
3-Chloro-4-methoxyphenyl4-Phenoxyphenyl
2-Isopropoxyphenyl4-Benzoylphenyl
4-IsopropoxyphenylIndolin-1-yl
2-(Triptoreline)phenyl2,3-Dihydrobenzo[1,4]dioxin-6-yl
3-(Triptoreline)phenylBenzo[1,3]dioxol-5-yl
4-(Triptoreline)phenyl4-(1H-Pyrrol-1-yl)phenyl
4-Phenylpiperidine-1-yl1,2,3,4-Tetrahydroisoquinoline-2-yl
4-Benzylpiperidine-1-yl

Table 2
R3X4 R3X4
PhenylCH23-(Triptoreline)phenylO
PhenylSN=SN4-(Triptoreline)phenylO
PhenylC≡C bonds3-Fluoro-4-wereO
PhenylAbout4-fluoro-2-wereO
PhenylS3-Chloro-4-forfinalO
PhenylNH5-Chloro-2-wereO
Phenyl(CH2)23-(Trifluoromethyl)phenylO
Phenyl(CH2)34-(Trifluoromethyl)phenylO
Phenyl(CH2)42,3-Dihydro what Enzo[1,4]dioxin-6-yl O
PhenylCH2OBenzofuran-5-ylO
Phenyl(CH2)2OBenzothiophen-5-ylO
Phenyl(CH2)3OCyclohexyl(CH2)2
PhenylCH2SCyclohexyl(CH2)3
PhenylSCH22-WereSN=SN
CyclohexylCH=CH4-ForfinalSN=SN
CyclohexylCH2CH=CH3-Fluoro-4-wereSN=SN
CyclohexylO3-NitrophenylSN=SN
2-forfinalO 4-AcetylphenylSN=SN
3-ForfinalO3-MethoxyphenylSN=SN
4-ForfinalO4-MethoxyphenylSN=SN
2,3-DifferenlO3-ChlorophenylSN=SN
2,4-DifferenlO2,3-Dihydrobenzo[1,4]dioxin-6-ylSN=SN
2.5-DifferenlOBenzofuran-5-ylSN=SN
2,6-DifferenlOBenzothiophen-5-ylSN=SN
3,4-DifferenlOBenzo[1,3]dioxol-5-ylSN=SN
3,5-DifferenlO2,1,3-Benzothiadiazole-4-ylSN=SN
2-ChlorophenylO 4-(Trifluoromethyl)phenylSN=SN
3-ChlorophenylO2,4-DifferenlSN=SN
4-ChlorophenylO3,5-DifferenlSN=SN
2,3-DichlorophenylO3,5-DichlorophenylSN=SN
2,4-DichlorophenylO4-HydroxyphenylSN=SN
2,5-DichlorophenylO4-(Triptoreline)phenylSN=SN
2,6-DichlorophenylO4-NitrophenylSN=SN
3,4-DichlorophenylO2-Were(CH2)2
3,5-DichlorophenylO4-Forfinal(CH2)2
3-NitrophenylO 3-fluoro-4-were(CH2)2
4-NitrophenylO4-Ethylphenyl(CH2)2
2-WereO3-Methoxyphenyl(CH2)2
3-WereO4-(Trifluoromethyl)phenyl(CH2)2
4-MethylenicO3-Chlorophenyl(CH2)2
2,3-DimetilfenilOBenzofuran-5-yl(CH2)2
2,6-DimetilfenilO3,5-Differenl(CH2)2
3,4-DimetilfenilO4-(Triptoreline)phenyl(CH2)2

C=O
Table 3
X1X2-X3R2X1X2-X3R2
C=OLinkCyclohexylC=OLinkBenzofuran-5-yl
C=OLink2-ForfinalC=OLinkBenzothiophen-2-yl
C=OLink3-ForfinalC=OLinkBenzothiophen-3-yl
C=OLink4-ForfinalC=OLinkBenzothiophen-5-yl
C=OLink2,4-DifferenlC=OLinkBenzothiazol-2-yl
C=OLink2,6-DifferenlC=OLinkBenzo[1,3]dioxol-5-yl
C=OLink3,4-DifferenlC=OLink2,3-Dihydrobenzo[1,4]
dioxin-6-yl
C=OLink3,5-DifferenlC=OLink6-Morpholinopropan-3-yl
C=OLink2-ChlorophenylC=OLink1-Phenyl-1H-pyrazole-5-yl
C=OLink3-ChlorophenylC=OLink6-(piperidine-1-yl)pyridine-3-yl
C=OLink4-ChlorophenylC=OLink6-(1H-Pyrrol-1-yl)pyridine-3-yl
C=O Link2,4-DichlorophenylC=OLink5-(1H-Pyrrol-1-yl)pyridine-3-yl
C=OLink2,6-DichlorophenylC=OLink2-(1H-Pyrrol-1-yl)pyridine-4-yl
C=OLink3,4-DichlorophenylC=OLink3-Phenylisoxazol-5-yl
C=OLink3,5-DichlorophenylC=OLink3-Phenyl-1H-pyrazole-5-yl
C=OLink2-WereC=OLink6-phenylpyrimidine-4-yl
C=OLink3-WereC=OLink2-(Trifluoromethyl)
phenyl
C=OLink 4-WereC=OLink3-(Trifluoromethyl)
phenyl
C=OLink2,3-DimetilfenilC=OLink4-(Trifluoromethyl)
phenyl
C=OLink3,4-DimetilfenilC=OLink2,4-Bis(trifluoromethyl)
phenyl
C=OLink3, 5dimethylphenylC=OLink3,5-Bis(trifluoromethyl)
phenyl
C=OLink3-NitrophenylC=OCH=CH(E)Phenyl
C=OLink4-NitrophenylC=OCH=CH(E)3,4-Acid
C=OLink2-HydroxyphenylCH2Phenyl
C=OLink4-HydroxyphenylC=OCH2AboutPhenyl
C=OLink3-Biphenyl - C=OCH2CH=CH(E)Phenyl
C=OLink4-Biphenyl - C=OC(CH3)=CH(E)Phenyl
C=OLinkThiophene-2-ylC=O(CH2)2Phenyl
C=OLinkBenzofuran-2-ylC=O(CH2)3Phenyl
C=OPhenylSO2Link Phenyl
SO2SN=SNPhenyl

Table 4
X1X2-X3R2X1X2-X3R2
C=OLinkCyclohexylC=OLink2-Phenylthiazol-4-yl
C=OLink2-ForfinalC=OLinkBenzo[1,3]dioxol-5-yl
C=OLink3-ForfinalC=OLink2,3-dihydrobenzo[1,4]
dioxin-6-yl
C=O Link4-ForfinalC=OLink1-Methyl-1H-benzotriazol-5-yl
C=OLink2,4-DifferenlC=OLink6-Morpholinopropan-3-yl
C=OLink2,6-DifferenlC=OLink6-(piperidine-1-yl)pyridine-3-yl
C=OLink3,4-DifferenlC=OLink6-(1H-Pyrrol-1-yl)pyridine-3-yl
C=OLink3,5-DifferenlC=OLink5-(1H-Pyrrol-1-yl)pyridine-3-yl
C=OLink2-ChlorophenylC=OLink2-(1H-Pyrrol-1-yl)pyridine-4-yl
C=OConnectivity 3-ChlorophenylC=OLink5-(Thiophene-2-yl)pyridine-3-yl
C=OLink4-ChlorophenylC=OLink3-Phenylisoxazol-5-yl
C=OLink2,4-DichlorophenylC=OLink3-Phenyl-1H-pyrazole-5-yl
C=OLink2,6-DichlorophenylC=OLink3-(1H-Pyrrol-1-yl)phenyl
C=OLink3,4-DichlorophenylC=OLink4-(1H-Pyrrol-1-yl)phenyl
C=OLink3,5-DichlorophenylC=OLink3-(1H-pyrazole-1-yl)phenyl
C=OLink3-IU is oxyphenyl C=OLink2-(Trifluoromethyl)
phenyl
C=OLink4-MethoxyphenylC=OLink3-(Trifluoromethyl)
phenyl
C=OLink2-WereC=OLink4-(Trifluoromethyl)
phenyl
C=OLink3-WereC=OLink2,4-Bis(trifluoromethyl)
phenyl
C=OLink4-WereC=OLink3,5-Bis(trifluoromethyl)
phenyl
C=OLink2,3-DimetilfenilC=OCH=CH(E)Phenyl
C=OLink3,4-Dimetilfenil C=OCH=CH(E)3-Chlorophenyl
C=OLink3, 5dimethylphenylC=OCH=CH(E)4-Chlorophenyl
C=OLink2-Biphenyl - C=OCH=CH(E)3,4-Dichlorophenyl
C=OLink3-Biphenyl - C=OCH=CH(E)3-Methoxyphenyl
C=OLink4-Biphenyl - C=OCH=CH(E)Thiophene-2-yl
C=OLink4-MorpholinomethylC=OCH=CH(E)Benzo[1,3]dioxol-5-yl
C=OLink3-NitrophenylC=OCH=CH(E)3,4-Dimitar iphenyl
C=OLink4-NitrophenylC=OCH=CH(E)3-Nitrophenyl
C=OLink2-HydroxyphenylC=OCH=CH(E)4-Hydroxyphenyl
C=OLinkThiophene-2-ylC=OCH2CH=CH(E)Phenyl
C=OLinkBenzofuran-2-ylC=OC(CH3)=CH(E)Phenyl
C=OLinkBenzofuran-5-ylC=O(CH2)2Phenyl
C=OLinkBenzothiophen-2-ylC=O(CH2)3Phenyl
C=O LinkBenzothiophen-3-ylC=OCH2AboutPhenyl
C=OLinkBenzothiophen-5-ylSO2CH2Phenyl
C=OLinkBenzothiazol-2-ylSO2SN=SNPhenyl
C=OLink6-Phenylpyrimidine-4-yl

2-Biphenyl -
Table 5
X1X2-X3R2X1X2-X3R2
C=OLink2-ForfinalThe=o LinkBenzothiophen-5-yl
C=OLink3-ForfinalC=OLinkBenzothiazol-2-yl
C=OLink4-ForfinalC=OLinkBenzo[1,3]dioxol-5-yl
C=OLink2,4-DifferenlC=OLink2,3-Dihydrobenzo[1,4]
dioxin-6-yl
C=OLink2,6-DifferenlC=OLink4-Morpholinomethyl
C=OLink3,4-DifferenlC=OLink6-(piperidine-1-yl)pyridine-3-yl
C=OLink3,5-DifferenlC=OSV is z 6-(1H-Pyrrol-1-yl)pyridine-3-yl
C=OLink2-ChlorophenylC=OLink5-(1H-Pyrrol-1-yl)pyridine-3-yl
C=OLink3-ChlorophenylC=OLink2-(1H-Pyrrol-1-yl)pyridine-4-yl
C=OLink4-ChlorophenylC=OLink3-Phenylisoxazol-5-yl
C=OLink2,4-DichlorophenylC=OLink3-Phenyl-1H-pyrazole-5-yl
C=OLink2,6-DichlorophenylC=OLink3-(1H-Pyrrol-1-yl)phenyl
C=OLink3,4-DichlorophenylC=OLink 4-(1H-Pyrrol-1-yl)phenyl
C=OLink3,5-DichlorophenylC=OLink6-phenylpyrimidine-4-yl
C=OLink3-MethoxyphenylC=OLink2-(Trifluoromethyl)phenyl
C=OLink4-MethoxyphenylC=OLink3-(Trifluoromethyl)phenyl
C=OLink2-WereC=OLink4-(Trifluoromethyl)phenyl
C=OLink3-WereC=OLink2,4-Bis(trifluoromethyl)
phenyl
C=OLink4-WereC=OLink3,5-Bis(trifluoromethyl)
Anil
C=OLink2,3-DimetilfenilC=OCH=CH(E)Phenyl
C=OLink3,4-DimetilfenilC=OCH=CH(E)3-Chlorophenyl
C=OLink3, 5dimethylphenylC=OCH=CH(E)4-Chlorophenyl
C=OLink3-NitrophenylC=OCH=CH(E)3,4-Dichlorophenyl
C=OLink2-HydroxyphenylC=OCH=CH(E)3-Methoxyphenyl
C=OLink4-HydroxyphenylC=OCH=CH(E)Thiophene-2-yl
C=OLinkC=OCH=CH(E)Benzo[1,3]dioxol-5-yl
C=OLink3-Biphenyl - C=OCH=CH(E)3,4-Acid
C=OLink4-Biphenyl - C=OCH=CH(E)3-Nitrophenyl
C=OLinkBenzofuran-2-ylC=OCH=CH(E)4-Hydroxyphenyl
C=OLinkBenzofuran-5-ylC=OCH2CH=CH(E)Phenyl
C=OLinkBenzothiophen-2-ylC=OC(CH3)=CH(E)Phenyl
C=OLinkBenzothiophen-3-ylC=O (CH2)2Phenyl
C=OPhenylSO2SN=SNPhenyl

Table 6
R3-X4--X2-X3-R2
3-Chlorophenyl4-Forfinal
3-Chlorophenyl4-Nitrophenyl
3-Chlorophenyl4-(Trifluoromethyl)phenyl
3-Chlorophenyl4-Hydroxyphenyl
3-Chlorophenyl2,3-Dimetilfenil
3-ChlorophenylBenzothiazol-2-yl
3-Chlorophenyl5-(1H-Pyrrol-1-yl)pyridine-3-yl
3-ChlorophenylBenzo[1,3]dioxol-5-yl
3-Chlorophenyl 2-Phenylphenyl
2,4-Differenl4-Forfinal
2,4-Differenl4-(Trifluoromethyl)phenyl
2,4-Differenl2,3-Dimetilfenil
2,4-DifferenlBenzothiazol-2-yl
2,4-Differenl5-(1H-Pyrrol-1-yl)pyridine-3-yl
2,4-Differenl2-Phenylphenyl
4-Hydroxyphenyl4-forfinal
4-Hydroxyphenyl4-(Trifluoromethyl)phenyl
4-HydroxyphenylBenzothiazol-2-yl
4-Hydroxyphenyl5-(1H-Pyrrol-1-yl)pyridine-3-yl
4-Hydroxyphenyl2-Phenylphenyl
Benzofuran-2-yl4-Forfinal
Benzofuran-2-yl4-(Trifluoromethyl)phenyl
Benzofuran-2-yl2,3-Dimetilfenil
Benzofur the h-2-yl Benzo[1,3]dioxol-5-yl
Benzofuran-2-yl2-Phenylphenyl
Benzo[1,3]dioxol-5-yl4-(Trifluoromethyl)phenyl
Benzo[1,3]dioxol-5-yl2,3-Dimetilfenil
Benzo[1,3]dioxol-5-ylBenzothiazol-2-yl
Benzo[1,3]dioxol-5-ylBenzo[1,3]dioxol-5-yl
Benzo[1,3]dioxol-5-yl2-Phenylphenyl
2-(3-Methoxyphenyl)vinyl4-Forfinal
2-(3-Methoxyphenyl)vinyl4-Nitrophenyl
2-(3-Methoxyphenyl)vinylBenzothiazol-2-yl
2-(3-Methoxyphenyl)vinyl2,3-Dimetilfenil
2-(3-Methoxyphenyl)vinylBenzo[1,3]dioxol-5-yl
2-(3-Methoxyphenyl)vinyl5-(1H-Pyrrol-1-yl)pyridine-3-yl
2-(3-Methoxyphenyl)vinyl2-Phenylphenyl

In addition, when l is the battle isomer (for example, optical isomer, geometric isomer, tautomer and the like) present in the compounds of the General formula [1] or their salts, the present invention includes these isomers and, in addition, includes a solvate, hydrates and crystals of various types.

Then, describes how to obtain the compounds of the present invention.

The compound of the present invention can be obtained by a combination of methods that are well known per se together, but, for example, can be obtained by methods of preparation, are shown below.

[Method of obtaining 1]

In the formula, R1arepresents carboxyamide group; R3arepresents phenyl, cycloalkyl, cycloalkenyl or monocyclic heterocyclic or bicyclic heterocyclic group linked through a member of a ring carbon atom and any of these groups may be optionally substituted; R4represents a hydrogen atom or a lower alkyl group; X7represents alkylenes group which may be optionally substituted; L1represents a leaving group; and R2X1X2and X3have the values specified above.

As compounds of General formula [3a] are known, for example, pyridine-3-baronova acid, 3-(methanesulfonamide)phenylboron the traveler acid, thiophene-2-baronova acid, benzofuran-2-baronova acid and 3-methoxyphenylalanine acid. As compounds of General formula [3b] is known, for example, 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan. In addition, compounds of General formula [3a] and [3b] can be obtained from the relevant halogenoalkane method, for example, described in JP-A-2003-206290.

Compounds of General formula [1a] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [3a] or [3b] in the presence or in the absence of base, in the presence of a palladium catalyst and in the presence or in the absence of ligand.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; aromatic hydrocarbons such as benzene, toluene and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; ethers, such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; ketones, such as acetone and 2-butanone; NITRILES, such as acetonitrile; esters such as ethyl acetate and BU is ylacetic, and sulfoxidov, such as dimethylsulfoxide, and to apply these solvents may be optionally mixed.

Examples of a base, optionally used in this reaction include inorganic bases such as sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and tribalistic, and organic bases such as triethylamine and diisopropylethylamine. The used amount of the base may be 1-50 mol, preferably 2-5 mol per mol of compound of General formula [2].

Used in this reaction, the palladium catalyst include palladium metal, such as palladium on coal and palladium black; inorganic palladium salt such as palladium chloride; organic palladium salt such as palladium acetate; palladiaanse complex such as tetrakis(triphenylphosphine)palladium(0), bis(triphenylphosphine)palladium(II)chloride, 1,1'-bis(diphenylphosphino)ferienparadies(II)chloride and Tris(dibenzylideneacetone)dipalladium(0) and immobilized on the polymer palladiaanse complex, such as applied to the polymer bis(acetato)triphenylphosphine(II) and deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II), and these catalysts can be used in combination. The applied amount of the palladium catalyst may be within 0.00001 to 1 mol, predpochtite the flax of 0.001-0.1 mol per mol of compound of General formula [2].

The ligand, optionally used in this reaction includes trialkylphosphine, such as trimethylphosphine and three-tert-butylphosphine; tricyclohexylphosphine, such as tricyclohexylphosphine; triarylphosphine, such as triphenylphosphine and trailerteen; trialkylphosphine, such as trimethylphosphite, triethylphosphite and tributylphosphite; tricyclohexylphosphine, such as tricyclohexylphosphine; triarylphosphine, such as triphenylphosphite; salt imidazole, such as chloride, 1,3-bis-(2,4,6-trimetilfenil)imidazole; diketones such as acetylacetone and activerelation; amines, such as trimethylamine, triethylamine, Tripropylamine and triisopropanolamine; 1,1'-bis(diphenylphosphino)ferrocene, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl, 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 2-(di-tert-butylphosphino)biphenyl, these ligands can optionally be used in combination. The applied amount of the ligand can be within 0.00001 to 1 mol, preferably 0.001 to 0.1 mol per mol of compound of General formula [2].

The applied amount of the compounds of General formula [3a] or [3b] can be 1-50 mol, preferably 1-2 mol per mol of compound of the formula [2].

This reaction can be preferably carried out in an atmosphere of inert gas (e.g. nitrogen, argon) at 40-170°C during the 1 minute to 96 hours.

[Method of obtaining 2]

In the formula, R3brepresents phenyl or monocyclic heterocyclic or bicyclic heterocyclic group associated with a member of a ring carbon atom and any of these groups may be optionally substituted; and R5represents a lower alkyl group; R1a, R2X1X2X3and L1have the same meanings as indicated above.

As compounds of General formula [4] are known, for example, 2-(tributylamine)thiazole and 2-(tributylamine)furan.

Compounds of General formula [1b] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [4] in the presence or in the absence of silver oxide and in the presence of palladium catalyst.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include aromatic hydrocarbons such as benzene, toluene and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; ethers, such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; NITRILES, such as acetonitrile, and sulfoxidov, such as di is ethylsulfonyl, to apply these solvents may be optionally mixed.

Used in this reaction, the palladium catalyst includes palladianism complexes such as tetrakis(triphenylphosphine)palladium(0), bis(triphenylphosphine)palladium(II)chloride, 1,1'-bis(diphenylphosphino)ferienparadies(II)chloride and Tris(dibenzylideneacetone)dipalladium(0) and immobilized on the polymer palladiaanse complex, such as applied to the polymer bis(acetato)triphenylphosphine(II) and deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II), and these catalysts can optionally be used in combination. The applied amount of the palladium catalyst may be within 0.00001 to 1 mol, preferably 0.001 to 0.1 mol per mol of compound of General formula [2].

The amount of silver oxide, optionally used in this reaction may be 1-50 mol, preferably 1-10 mol, per mol of compound of General formula [2].

The applied amount of the compounds of General formula [4] can be 1-50 mol, preferably 1-2 mol per mol of compound of General formula [2].

This reaction can be preferably carried out in an atmosphere of inert gas (e.g. nitrogen, argon) at 40-170°C for from 1 minute to 96 hours.

[Method of obtaining 3]

In the formula, R3crepresents phenyl,cycloalkyl or monocyclic heterocyclic or bicyclic heterocyclic group, associated with is a member of the ring carbon atom and any of these groups may be optionally substituted; X2Arepresents alkylamino group which may be optionally substituted or a bond; X6Arepresents alkenylamine or alkynylamino group which may be optionally substituted; X6brepresents alkylenes group which may be optionally substituted; R1a, R2, R3aX1X2X3X5and L1have the same meanings as indicated above.

As compounds of General formula [5] are known, for example, styrene, Olivenza, 4-phenyl-1-butene, vinylcyclohexane and allylcyclohexane. In addition, compounds of General formula [5] can be obtained by, for example, described in “Jikken Depending Kouza”, 4thedition, Vol. 19, pp. 298-361, 1992, Maruzen, or similar method.

(3-1)

When X6Arepresents alkenylamine group which may be optionally substituted, a compound of General formula [1c] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [5] in the presence or in the absence of base, in the presence or in the absence of a phase transfer catalyst, in the presence or in the absence of ligand and in the presence of palladium catalyst.

Used in this reaction the solvent to ncrete limit, if he does not exert an adverse influence on the reaction, and examples include water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; aromatic hydrocarbons such as benzene, toluene and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; ethers, such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; ketones, such as acetone and 2-butanone; NITRILES, such as acetonitrile; esters such as ethyl acetate and butyl acetate, and sulfoxidov, such as dimethylsulfoxide, to apply these solvents may be optionally mixed.

Examples of a base, optionally used in this reaction include inorganic bases such as sodium hydride, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and tribalistic, and organic bases, such as sodium acetate, potassium acetate, tert-piperonyl sodium, triethylamine, diisopropylethylamine, tributylamine and N,N-dicyclohexylamine. The used amount of the base may be 1-50 mol, preferably 2-5 mol per mol of compound of General formula [2].

Examples of phase transfer catalyst, it is not necessarily Amenemope in this reaction, include Quaternary ammonium salts such as the chloride of Tetramethylammonium, chloride designed, chloride of benzyltriethylammonium, chloride of benzyltrimethylammonium, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hydrosulfate and chloride of trioctylamine; chloride N-laurylamine, chloride, N-lauryl-4-picoline, chloride N-laurylamine and chloride N-benzylamine. Used by a number of interphase catalyst may be 0.01 to 50 mol, preferably 0.1 to 5 mol per mol of compound of the formula [2].

The ligand, optionally used in this reaction includes trialkylphosphine, such as trimethylphosphine and three-tert-butylphosphine; tricyclohexylphosphine, such as tricyclohexylphosphine; triarylphosphine, such as triphenylphosphine and trailerteen; trialkylphosphine, such as trimethylphosphite, triethylphosphite and tributylphosphite; tricyclohexylphosphine, such as tricyclohexylphosphine; triarylphosphine, such as triphenylphosphite; salt imidazole, such as chloride, 1,3-bis-(2,4,6-trimetilfenil)imidazole; diketones such as acetylacetone and activerelation; amines, such as trimethylamine, triethylamine, Tripropylamine and triisopropanolamine; 1,1'-bis(diphenylphosphino)ferrocene, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 2-(di-tert-butylphosphino)biphenyl, moreover, these compounds can optionally be used in combination. The applied amount of the ligand can be within 0.00001 to 1 mol, preferably 0.001 to 0.1 mol per mol of compound of General formula [2].

The examples used in this reaction, the palladium catalyst include palladium metal, such as palladium on coal and palladium black; inorganic palladium salt such as palladium chloride; organic palladium salt such as palladium acetate; palladiaanse complex such as tetrakis(triphenylphosphine)palladium(0), bis(triphenylphosphine)palladium(II)chloride, 1,1'-bis(diphenylphosphino)ferienparadies(II)chloride, (E)-di-(µ-acetato)bis-(o-(di-o-tolylphosphino)benzyl)dipalladium(II) and Tris(dibenzylideneacetone)dipalladium(0) and immobilized on the polymer palladiaanse complex, such as applied to the polymer bis(acetato)triphenylphosphine(II) and deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II), and these catalysts can be used in combination. The applied amount of the palladium catalyst may be within 0.00001 to 1 mol, preferably 0.001 to 0.1 mol per mol of compound of General formula [2].

The applied amount of the compounds of General formula [5] can be 1-50 mol, preferably 1-2 mol per mol of compound of General formula [2].

This reaction can be preferably carried out in the atmosphere inert gas (for example, nitrogen, argon) at 40-170°C for from 1 minute to 24 hours.

(3-2)

When X6Arepresents alkynylamino group which may be optionally substituted, a compound of General formula [1c] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [5] in the presence or in the absence of base, in the presence or in the absence of a copper catalyst and in the presence of palladium catalyst.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; aromatic hydrocarbons such as benzene, toluene and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; ethers, such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; ketones, such as acetone and 2-butanone; NITRILES, such as acetonitrile; esters such as ethyl acetate and butyl acetate, and sulfoxidov, such as dimethylsulfoxide, and to apply these solvents may be optionally mixed.

Examples of a base, optionally used is given reaction, include inorganic bases such as sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and tribalistic, and organic bases such as triethylamine and diisopropylethylamine. The used amount of the base may be 1-50 mol, preferably 2-5 mol per mol of compound of General formula [2].

Examples of the copper catalyst, optionally used in this reaction include copper bromide and copper iodide. The applied amount of the copper catalyst may be 0.01 to 50 mol, preferably 0.1 to 5 mol per mol of compound of General formula [2].

The examples used in this reaction, the palladium catalyst include palladium metal, such as palladium on coal and palladium black; inorganic palladium salt such as palladium chloride; organic palladium salt such as palladium acetate; palladiaanse complex such as tetrakis(triphenylphosphine)palladium(0), bis(triphenylphosphine)palladium(II)chloride, 1,1'-bis(diphenylphosphino)ferienparadies(II)chloride and Tris(dibenzylideneacetone)dipalladium(0) and immobilized on the polymer palladiaanse complex, such as applied to the polymer bis(acetato)triphenylphosphorane(II) and deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II), and these catalysts can be used in combination. Premiereelements palladium catalyst may be within 0.00001 to 1 mol, preferably 0.001 to 0.1 mol per mol of compound of General formula [2].

The applied amount of the compounds of General formula [5] can be 1-50 mol, preferably 1-2 mol per mol of compound of General formula [2].

This reaction can be preferably carried out in an atmosphere of inert gas (e.g. nitrogen, argon) at 10-170°C for from 1 minute to 24 hours.

(3-3)

Compounds of General formula [1d] can be obtained by reduction of compound of General formula [1c].

Examples of reduction reaction includes the reaction of catalytic hydrogenation using a metal catalyst.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; NITRILES, such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate; and carbó the OIC acid, such as acetic acid, and heteroaromatic compounds such as pyridine, and to apply these solvents may be optionally mixed.

Examples of the metal catalyst used in this reaction include metal palladium such as palladium on coal and palladium black; palladium salt such as palladium oxide and palladium hydroxide, metal Nickel, such as Raney Nickel and platinum salts, such as platinum oxide. The used amount of the metal catalyst may be 0.001 to 5-fold amount (weight/weight), preferably 0.1 to 1, a multiple of the number (mass/mass) for compounds of General formula [1c].

Examples of the reducing agent used in this reaction include hydrogen, formic acid, formate, such as sodium formate, ammonium formate and formate of triethylamine; cyclohexene and cyclohexadiene. The applied amount of the reducing agent can be 2-100 mol, preferably 2-10 mol, per mol of compound of General formula [1c].

This reaction can be conducted at 0-200°C., preferably at 0 to 100°C for from 1 minute to 24 hours.

[Method 4]

"In the formula X5Arepresents an oxygen atom, a sulfur atom or aminogroup, which may be optionally protected; R1a, R2, R3a1X2X3X6and L1have the same meanings as indicated above.

As compounds of General formula [6] are known, for example, aniline, benzylamine, phenol, thiophenol and benzylmercaptan. In addition, for example, compounds of General formula [6] can be obtained as usual from the respective halogenoalkane.

(4-1)

The compound of General formula [1e] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [6] the method for producing a (3-1).

(4-2)

When X5Arepresents an oxygen atom, the compound of General formula [1e] can be obtained by reaction of the compound of the formula [2] with the compound of General formula [6] in the presence or in the absence of a base and in the presence of a copper catalyst.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include aromatic hydrocarbons such as benzene, toluene and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; ethers, such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; ketones, such as acetone and 2-butane is n; NITRILES, such as acetonitrile; esters such as ethyl acetate and butyl acetate, and sulfoxidov, such as dimethylsulfoxide, and to apply these solvents may be optionally mixed.

Examples of a base, optionally used in this reaction include sodium hydride and sodium. The used amount of the base may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [2].

Examples of the copper catalyst used in this reaction include copper powder and copper iodide. The applied amount of the copper catalyst may be within 0.00001 to 1 mol, preferably 0.01 to 1 mol per mol of compound of General formula [2].

The applied amount of the compounds of General formula [6] can be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [2].

This reaction can be preferably carried out at 40-200°C for from 30 minutes to 72 hours.

[Method of obtaining 5]

"In the formula L2represents a leaving group; R1a, R2, R3aX1X2X3and X6ahave the same meanings as indicated above.

As compounds of General formula [8a] are known, for example, 2-odolwa, 3-odolwa, 3-ignitrons and 6-iodine-2,3-dihydrobenzo[1,4]dioxin.

Compounds of General formula [1f] can be obtained by reaction with the organisations of General formula [7] with the compound of General formula [8a] the method for producing a (3-1) or (3-2).

[Method of obtaining 6]

In the formula, R1a, R2, R3X1X2X3and X4have the same meanings as indicated above.

(6-1)

When X1represents a carbonyl group, the compound of General formula [1g] can be obtained by amidation of the compounds of General formula [9]. Specifically included the use of gelegenheid acid in the presence or in the absence of substrates, the method using acid anhydride in the presence or in the absence of the grounds and the like.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples of it include amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; NITRILES, such as acetonitrile; ketones, such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate, and sulfoxidov, such as dimethylsulfoxide, and to apply these solvents may be optionally mixed.

Examples of gelegenheid acid used in this reaction include benzoyl chloride, benzylbromide, 2,4-differentiald, 2-aftercare, diphenylacetylene, 2,3-dihydrobenzo[1,4]dioxin-6-carbonylchloride, cyclohexanecarbonitrile, cyclopentanecarbonitrile, (E)-3-phenylacrylate, phenoxyacetophenone, 2-frailcare, 1-benzofuran-2-carbonylchloride, 2-troillard, nicotinergic and picolinate. In addition, halogenmethyl acid can be obtained by reaction of the compound represented by the General formula [38].

[Formula 2]

In the formula, R2X2and X3have the same meanings as above, with thionyl chloride, oxalylamino or the like. Used by a number of gelegenheid acid may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [9].

Examples of the acid anhydride used in the reaction include benzoic anhydride. In addition, the acid halides can be obtained from the corresponding carboxylic acid by the method, for example, described in “Shin Jikken Depending Kouza, Vol. 14, pp. 1120-1133, 1977, Maruzen, or similar method. The used amount of the acid anhydride may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [9].

Examples of a base, optionally used in this reaction, R is t inorganic bases, such as sodium bicarbonate, sodium carbonate, potassium carbonate and cesium carbonate, and organic bases such as triethylamine and diisopropylethylamine. The used amount of the base may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [9].

This reaction can be performed in the usual manner at a temperature of from -78 to 100°C., preferably at 0-80°C for from 10 minutes to 24 hours.

(6-2)

When X1represents sulfonyloxy group, the compound of General formula [1g] can be obtained by sulfonamideubul compounds of General formula

[9]. Specifically, includes a method of applying sulphonylchloride in the presence or in the absence of base.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples of it include amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; NITRILES, such as acetonitrile; ketones, such as acetone and 2-butanone; esters such as ethyl the Etat and butyl acetate, sulfones such as sulfolane, and sulfoxidov, such as dimethylsulfoxide, and to apply these solvents may be optionally mixed.

Examples of sulphonylchloride used in this reaction include benzosulphochloride and α-toluensulfonate. In addition, sulfonylmethane can be obtained from the corresponding sulfonic acid by the method, for example, described in “Shin Jikken Depending Kouza, Vol. 14, pp. 1784-1792, 1978, Maruzen, or similar method. Used by a number of sulphonylchloride may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [9].

Examples of a base, optionally used in this reaction include inorganic bases such as sodium bicarbonate, sodium carbonate, potassium carbonate and cesium carbonate, and organic bases such as triethylamine and diisopropylethylamine. The used amount of the base may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [9].

This reaction can be performed in the usual manner at a temperature of from -78 to 100°C., preferably at 0-80°C for from 10 minutes to 24 hours.

[Method of obtaining 7]

"In the formula X6srepresents alkylenes group which may be optionally substituted or a bond; L3represents a leaving group; R1a2,

R3aX1X2X3X5aand X6bhave the same meanings as above, provided that, if X6srepresents a bond, R3arepresents cycloalkyl group which may be optionally substituted".

As compounds of General formula [11a] are known, for example, benzylbromide and (2-bromacil)benzene. As compounds of General formula [11b] are known, for example, 3-phenyl-1-propanol and cyclohexanol.

(7-1)

Compounds of General formula [1h] can be obtained by reaction of compounds of General formula [10] with a compound of General formula [11a] in the presence of a base.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples of it include amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; NITRILES, such as acetonitrile; ketones, such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate, sulfones, suchas sulfolan, and sulfoxidov, such as dimethylsulfoxide, and to apply these solvents may be optionally mixed.

The applied amount of the compounds of General formula [11] can be 1-20 mol, preferably 1-5 mol per mol of compound of General formula [10].

Examples of the base used in this reaction include organic amines, such as dimethylaminopyridine, triethylamine and pyridine; hydrides of alkali metals, such as sodium hydride and carbonates of alkali metals such as potassium carbonate and sodium carbonate.

The used amount of the base may be 1-20 mol, preferably 1-5 mol per mol of compound of General formula [10].

This reaction can be performed in the usual way at 0-200°C., preferably at 25-150°C for from 10 minutes to 24 hours.

(7-2)

When X5Arepresents an oxygen atom or a sulfur atom, the compound of General formula [1h] can be obtained by reaction Mitsunobu between the compound of General formula [10] and the compound of General formula [11b] in the presence of azodicarbonamide compounds and phosphine.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as dioxane, tetrahydrofuran, anisole, dimethyl ether d is ethylene glycol, onomatology ether of ethylene glycol and dimethyl ether of ethylene glycol; esters such as methyl acetate, ethyl acetate and butyl acetate; NITRILES such as acetonitrile; amides such as N,N-dimethylformamide and N,N-dimethylacetamide; halogenated hydrocarbons such as chloroform, methylene chloride, and to apply these solvents may be optionally mixed.

Examples azodicarbonamide compounds used in this reaction include diethylazodicarboxylate, diisopropylsalicylic and azodicarbonamide. Used number azodicarbonamide connection can be 1-5 mol, preferably 1-3 mol per mol of compound of General formula [10].

Examples of the phosphines used in this reaction include triarylphosphine, such as triphenylphosphine, and trialkylphosphine, such as tributylphosphine. Used by a number of phosphines can be 1-5 mol, preferably 1-3 mol per mol of compound of General formula [10].

The applied amount of the compounds of General formula [11b] can be 1-5 mol, preferably 1-3 mol per mol of compound of General formula [10].

This reaction can be performed in the usual manner at a temperature from -20 to 120°C, preferably at 0-50°C. for from 30 minutes to 24 hours.

[Method of obtaining 8]

"In the formula X2bis a bond;X 3Arepresents an oxygen atom or a bond; X5brepresents an oxygen atom, sulfonyloxy group or a bond; R2, R3aand X1have the same meanings as indicated above.

The compound of General formula [1i] can be obtained by reaction of compounds of General formula [12] with an oxidizing agent in the presence or in the absence of acid or base in the presence or absence of salt.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include water; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; aliphatic hydrocarbons such as hexane and cyclohexane; pyridine, and to apply these solvents may be optionally mixed.

Examples of acid, optionally used in this reaction include mineral acids such as hydrochloric acid and sulfuric acid, and organic acids such as acetic acid. The used amount of the acid may be 1 to 1,000 mol per mol of compound of General formula [12].

Examples of a base, optionally used in this reaction include inorganic bases such as sodium hydroxide and potassium hydroxide, and an organic base, such as pyridine. The used amount of the base can b the th 1 to 1,000 mol per mol of compound of General formula [12].

Examples of salt, optionally used in this reaction include magnesium sulfate, ammonium sulfate and magnesium chloride. The applied amount of salt can be 1-50 mol, preferably 1-10 mol per mol of compound of General formula [12].

Examples of the oxidizing agent used in this reaction include chromate, such as chromium oxide (VI) and sodium dichromate and permanganate such as potassium permanganate permanganate barium, permanganate calcium and magnesium permanganate. The applied amount of oxidizing agent may be 1-50 mol, preferably 1-10 mol per mol of compound of General formula [12].

This reaction can be performed in the usual way at 0-150°C., preferably at 40-130°C for from 30 minutes to 48 hours.

[Method of obtaining 9]

"R3drepresents a monocyclic heterocyclic or bicyclic heterocyclic group connected through the nitrogen atom, which participates in the formation of rings, and this group may be optionally substituted; R1a, R2X1X2X3and L1have the same meanings as indicated above.

As compounds of General formula [13] are known, for example, pyrrolidine, piperidine, morpholine, pyrrole, indoline, isoindole, benzimidazole and indole.

The compound of General formula [1j] you can get the reaction the Oia compounds of General formula [2] with the compound of General formula [13] according to the method of obtaining 1.

[Method 10]

In the formula, R3erepresents cycloalkenyl group which may be optionally substituted; R3frepresents cycloalkyl group which may be optionally substituted; R1a, R2X1X2X2AX3and L1have the same meanings as indicated above.

As compounds of General formula [14] are known, for example, cyclopentene and cyclohexene. In addition, the compound of General formula [14] can be obtained by, for example, described in “Jikken Depending Kouza”, 4thedition, Vol. 19, pp. 53-298, 1992, Maruzen, or similar method.

(10-1)

The compound of General formula [1k] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [14] the method for producing a (3-1).

(10-2)

The compound of General formula [11] can be obtained by reduction of compound of General formula [1k] method for producing a (3-3).

[Method of obtaining 11]

“In the formula L2arepresents a chlorine atom, a bromine atom or an iodine atom; R1a, R2, R3bX1X2X3and X7have the same meanings as indicated above.

As compounds of General formula [8b] known are, for example, 2-odolwa, 3-iodoanisole, 3-ignitrons and 6-iodine-2,3-dihydrobenzo[1,4]dioxy is.

The compound of General formula [1b] can be obtained by reaction of compounds of General formula [15] with the compound of General formula [8b] according to the method of obtaining 1.

[Method of obtaining 12]

In the formula, R2, R3X1X2X3X6and X6shave the same meanings as indicated above.

The compound of General formula [1n] can be obtained by reduction of compound of General formula [1m] method for producing a (3-3).

[Method of obtaining 13]

In the formula, R2, R3X1X2X3X6aand X6bhave the same meanings as indicated above.

The compound of General formula [1] can be obtained by reduction of compound of General formula [1o] the method for producing a (3-3).

[Method of obtaining 14]

In the formula, R1a, R2, R3X1X2X3and X4have the same meanings as indicated above.

The compound of General formula [1q] can be obtained by removing protection from compounds of General formula [1g].

Examples of the reaction unprotect include hydrolysis using acid or base, the dealkylation reaction with salt and the reaction of reductive dealkylation, which includes a hydrogenation reaction using a metal catalyst.

When the minimum level of acid hydrolysis using acid include formic acid, hydrochloric acid, sulfuric acid, Hydrobromic acid, triperoxonane acid, aluminium chloride and audirovannyj trimethylsilane. The used amount of the acid may be 1-100000 mol, preferably 1 to 1,000 mol per mol of compound of General formula [1g].

Examples of the base hydrolysis with the use of the base include inorganic bases such as sodium hydroxide, potassium hydroxide and lithium hydroxide; organic bases, such as sodium methoxide, ethoxide sodium tert-piperonyl potassium; carbonates such as potassium carbonate and sodium carbonate and tetrabutylammonium fluoride. The used amount of the base may be 1 to 1,000 mol, preferably 1-50 mol per mol of compound of General formula [1g].

Examples of salts in the reaction dealkylation using salt include lithium iodide and sodium chloride. The applied amount of salt can be 1-100 mol, preferably 1-10 mol per mol of compound of General formula [1g].

The reaction of reductive dealkylation, comprising the reaction of catalytic hydrogenation using a metal catalyst, can be carried out according to the method of obtaining (3-3).

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include water; alcohols such as methanol, this is Nol, 2-propanol and 2-methyl-2-propanol; ethers such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; NITRILES such as acetonitrile; aliphatic hydrocarbons such as hexane and cyclohexane; aromatic hydrocarbons such as benzene, toluene and xylene; sulfoxidov, such as dimethyl sulfoxide; amides such as N,N-dimethylformamide; nitromethane, pyridine, to apply these solvents may be optionally mixed.

This reaction can be performed in the usual manner at a temperature of from -78 to 100°C., preferably at 0-80°C for from 10 minutes to 24 hours.

[Method of obtaining 15]

“In the formula X5srepresents sulfonyloxy group or sulfonyloxy group; R1, R2, R3X1X2X3and X6have the same meanings as indicated above.

The compound of General formula [1s] can be obtained by reaction of compounds of General formula [1r] with an oxidizing agent.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include water; halogenated hydrocarbons such as methyl shall chlorid, chloroform and dichloroethane; aliphatic hydrocarbons such as hexane and cyclohexane, pyridine, and to apply these solvents may be optionally mixed.

Examples of the oxidizing agent used in this reaction include hydrogen peroxide; percolate, such as peroxidasa acid, derbentina acid and m-chloroperbenzoic acid; peroxides, such as tert-butylperoxide and metaperiodate sodium. The applied amount of oxidizing agent may be 1-50 mol, preferably 1-10 mol per mol of compound of General formula [1r].

This reaction can be performed in the usual way at 0-150°C., preferably at 10-100°C for from 30 minutes to 48 hours.

[Method 16]

In the formula, R1, R2, R3aX1X2X3X5sand X6have the same meanings as indicated above.

The compound of General formula [1u] can be obtained by reaction of compounds of General formula [1t] with an oxidizing agent according to the method of obtaining 15.

Thus obtained compounds of General formula [1a], [1b], [1c] [1d], [1e], [1f], [1g], [1h], [1i], [1j], [1k], [1l], [1n], [1o], [1p], [1q], [1r], [1s], [1t] and [1u] or their salts can be converted into other compounds of General formula [1] or salt, for this, they are subjected to reactions known per se, such as condensation, addition, oxidation, recovery, paragroup the bottom, substitution, halogenoalkane, dehydration and hydrolysis or, if necessary, combinations of these reactions.

In addition, when there are any isomers (for example, optical isomer, geometric isomer, tautomer and the like) connections when receiving the above methods, you can also apply these isomers and you can also apply a solvate, hydrates and crystals of various types of such compounds.

The following describes methods of producing compounds of the General formula[2], [7], [9],

[10], [12], [15] and [38], which are the starting compounds in the formation of compounds of the present invention.

[Method of obtaining And]

In the formula, R1a, R2X1X2X3and L1have the same meanings as indicated above.

As compounds of General formula [16] are known, for example, 4-chloro-2-nitrobenzoic acid and 4-bromo-2-nitrobenzoic acid.

(A-1).

The compound of General formula [17] can be obtained by esterification compounds of General formula [16]. This reaction can be carried out by the method described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 369-453, 1999, John Wiley & Sons, INC., or similar method. Specifically included are methods using an alkylating agent in the presence or in the absence of a phase transfer catalyst, in the presence of a base, the method through education Gal which of genamerica acid compounds of General formula [16].

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include aromatic hydrocarbons such as benzene, toluene and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; ethers, such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; ketones, such as acetone and 2-butanone; NITRILES, such as acetonitrile; esters such as ethyl acetate and butyl acetate, and sulfoxidov, such as dimethyl sulfoxide; to apply these solvents may be optionally mixed.

Examples of phase transfer catalyst, optionally used in this reaction include Quaternary ammonium salt, such as chloride of Tetramethylammonium, chloride designed, chloride of benzyltriethylammonium, chloride of benzyltrimethylammonium and tetrabutylammonium bromide. The applied amount of salt may be 0.01 mol or more, preferably 0.1 to 5 mol per mol of compound of General formula [16].

Examples of the base used in this reaction include inorganic bases such as sodium carbonate, potassium carbonate and carbonate price is s, and organic bases such as triethylamine, pyridine, dimethylaminopyridine and N-methylmorpholine. The used amount of the base may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [16].

Examples of alkylating agent used in this reaction include methyliodide, ethyliodide, dimethylsulfate, 2-bromo-2-methylpropan, benzylchloride and benzylbromide. The applied amount of the alkylating agent may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [16].

This reaction can be performed in the usual way when 0-170°C for a time from 1 minute to 24 hours.

For example, in the method carried out through the formation of gelegenheid acid, the compound of General formula [16] can be subjected to reaction with thionyl chloride, oxalylamino or the like for turning it into gelegenheid acid and then subjected to reaction with alcohols, such as methanol, ethanol, benzyl alcohol, in the presence or in the absence of base.

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; ethers, such as dioxane, tetrahydro the Russian Academy of Sciences, the anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; ketones, such as acetone and 2-butanone; NITRILES, such as acetonitrile; esters such as ethyl acetate and butyl acetate, and sulfoxidov, such as dimethyl sulfoxide; and to apply these solvents may be optionally mixed.

Examples of a base, optionally used in this reaction include inorganic bases such as sodium carbonate, potassium carbonate and cesium carbonate, and organic bases such as triethylamine, pyridine, dimethylaminopyridine and N-methylmorpholine. The used amount of the base may be 1-50 mol, preferably 1-5 mol per mol of compound of General formula [16].

This reaction can be performed in the usual way when 0-170°C for a time from 1 minute to 24 hours.

(A-2)

The compound of General formula [18] can be obtained by reduction of compound of General formula [17]. This reaction can be carried out by the method described in Richard C. Larock et al., Comprehensive Organic Transformations, second edition, pp. 823-827, 1999, John Wiley & Sons, INC., or similar method. Specifically, included the reaction of catalytic hydrogenation using a metal catalyst and reaction recovery with the use of metal, such as iron or zinc.

When the compound of General formula [17] is subjected to reaction catalic the ical hydrogenation, it can be done by way of obtaining (3-3).

Used in this reaction the solvent is not specifically limited, if it has no adverse effect on the reaction, and examples include water; alcohols such as methanol, ethanol, 2-propanol and 2-methyl-2-propanol; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and 1-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as dioxane, tetrahydrofuran, anisole, dimethyl ether of ethylene glycol, dimethyl ether of diethylene glycol and diethyl ether of diethylene glycol; NITRILES, such as acetonitrile; ketones such as acetone and 2-butanone; esters such as ethyl acetate and butyl acetate, and to apply these solvents may be optionally mixed.

Examples of the metal used in this reaction include iron, zinc, tin, and tin chloride (II). The used amount of the base may be 1-50 mol, preferably 1-10 mol per mol of compound of General formula [17].

Examples of acid, optionally used in this reaction include hydrogen chloride, hydrogen bromide and acetic acid. The used amount of the acid may be 0.001 to 100-fold amount (weight/volume), preferably from 0.01 to 20-fold amount (weight/is the volume), the amount of compounds of General formula [17].

This reaction can be conducted at 0-200°C., preferably 0-100°C. for a time from 1 minute to 24 hours.

(A-3)

The compound of General formula [2] can be obtained by amidation or sulfonamideubul compounds of General formula [18] according to the method of obtaining 6.

[Method of obtaining In]

In the formula, R1a, R2X1X2bX3aand L1have the same meanings as indicated above.

As compounds of General formula [19] is known, for example, 5-iodine-2-methylaniline.

(B-1)

The compound of General formula [20] can be obtained by amidation or sulfonamideubul compounds of General formula [19] method for producing a 6.

(B-2)

The compound of General formula [21] can be obtained by reaction of compounds of General formula [20] with an oxidizing agent according to the method of obtaining 8.

(B-3)

The compound of General formula [2A] can be obtained by esterification compounds of General formula [21] according to the method of obtaining (a-1).

[Method of obtaining]

In the formula, R1a, R2, R4, R5X1X2X3X6AX7and L1have the same meanings as indicated above.

The compound of General formula [7] can be obtained by reaction of a combination of compounds of General formula [2] with the compound of General formula [22A] the method for producing a 2. In addition to t the th, it can also be obtained by reaction of compounds of General formula [2] with the compound of General formula [22b1] or General formula [22b2] getting 1.

[Method of obtaining D]

In the formula, R6represents acetylamino group; R1a, R2X1X2X3and L1have the same meanings as indicated above.

The compound of General formula [7a] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [22s] and then carrying out the reaction unprotect method for producing a (3-2).

Removing the protection can be carried out by the method described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 654-659, 1999, John Wiley & Sons, INC., or similar method.

[Method of obtaining E]

In the formula, R1a, R3and X5have the same meanings as indicated above.

As compounds of General formula [23] is known, for example, 2-nitro-4-phenoxybenzoic acid [WO03/033480].

(E-1)

The compound of General formula [24] can be obtained by esterification compounds of General formula [23] according to the method of obtaining (a-1).

(E-2)

The compound of General formula [9] can be obtained by reduction of compound of General formula [24] the method for producing a (3-3) or (a-2).

[Method of obtaining F]

In the formula, R 1a, R3a, R4X7and L1have the same meanings as indicated above.

(F-1)

The compound of General formula [25] can be obtained by reaction of compounds of General formula [17] with a compound of General formula [3A] or General formula [3b] by way of obtaining 1.

(F-2)

The compound of General formula [9b] can be obtained by reduction of compound of General formula [25] the method for producing a (3-3) or (a-2).

[Method of obtaining G]

In the formula, R1a, R3b, R5and L1have the same meanings as indicated above.

(G-1)

The compound of General formula [26] can be obtained by reaction of compounds of General formula [17] with a compound of General formula [4] according to the method of obtaining 2.

(G-2)

The compound of General formula [9c] can be obtained by reduction of compound of General formula [26] the method for producing a (3-3) or (a-2).

[Method of obtaining N]

In the formula, R6drepresents alkenylamine group which may be optionally substituted, R1a, R3a, R3cX6band L1have the same meanings as indicated above.

(N-1)

The compound of General formula [28] can be obtained by reaction of compounds of General formula [17] with a compound of General formula [27] the method for producing a (3-1).

(N-2)

The compound of General formula [9d] you can get a restore is the group of compounds of General formula [28] method for producing a (3-3).

[Method of obtaining I]

“In the formula L4represents a leaving group; R1a, R3a, R3cX5aand X6bhave the same meanings as indicated above.

As compounds of General formula [29] is known, for example, methyl-4-(methyl bromide)-2-nitrobenzoate. In addition, methyl-4-(methyl bromide)-2-nitrobenzoate can be obtained by esterification 4-(methyl bromide)-2-nitrobenzoic acid by a conventional method described in Journal of Medicinal Chemistry, Vol. 29, pp. 589-591, 1986.

(I-1).

The compound of General formula [31] can be obtained by reaction of compounds of General formula [29] with a compound of General formula [30] method for producing a (7-1).

(I-2)

The compound of General formula [9e] can be obtained by reduction of compound of General formula [31] a method for producing a (3-3) or (a-2).

[Method of obtaining J]

In the formula, R7represents (phenolic hydroxyl protective group or toolsedit group; R1a, R2X1X2X3and X5ahave the same meanings as indicated above.

As compounds of General formula [32] is known, for example, methyl-2-amino-4-methoxybenzoate [Journal of the Chemical Society, Perkin Transactions 1, Vol. 21, pp. 3261-3274, 1997].

(J-1)

The compound of General formula [33] can be obtained by amidation or self what nominirovana compounds of General formula [32] according to the method of obtaining 6.

(J-2)

The compound of General formula [10] can be obtained by removing the protective group from compounds of General formula [33]. The removal of the protective group of a phenolic hydroxyl can be, for example, by the method described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 249-287, 1999, John Wiley & Sons, INC., or similar method; removing the protective group of the thiol can be, for example, by the method described in W. Greene et al., Protective Groups in Organic Synthesis, third edition, pp. 454-493, 1999, John Wiley & Sons, INC., or similar method.

[How To get]

In the formula, R2, R3X1X2bX3aand X5bhave the same meanings as indicated above.

As compounds of General formula [34] is known, for example, 1-methyl-2-nitro-4-phenoxybenzoyl [Publication of International patent application wO02/078693].

(K-1)

The compound of General formula [35] can be obtained by reduction of compound of General formula [34] method for producing a (3-3) or (a-2).

(K-2)

The compound of General formula [12] can be obtained by amidation or sulfonamideubul compounds of General formula [35] according to the method of obtaining 6.

[Method of obtaining L]

In the formula, R1a, R2X1X2X3X7and L1have the same meanings as indicated above.

As compounds of General formula [36] of the local are, for example, bis(pinacolato)diboron, bis(neopentylglycol)diboron and bis(hexyleneglycol)diboron.

The compound of General formula [15] can be obtained by reaction of compounds of General formula [2] with the compound of General formula [36] according to the method of obtaining 1.

[Method of obtaining M]

In the formula, R1brepresents carboxyamide group; R2X2and X3have the same meanings as indicated above.

As compounds of General formula [37] is known, for example, methyl-2-(1H-pyrrol-1-yl)pyridine-4-carboxylate [Publication of International patent application WO9426709].

The compound of General formula [38] can be obtained by removing protection from compounds of General formula [37] according to the method of obtaining 14.

In the compounds used in the methods of obtaining the above compounds, which may be in salt form, can be applied in the form of a salt. Examples of these salts include salts, which are similar to the salts of the compounds of General formula [1].

When there are any isomers (for example, optical isomer, geometric isomer, tautomer and the like) connections when receiving the above methods, you can also apply these isomers. In addition, when there are solvate, hydrates and various types of crystals, you can also apply these solvate, hydrates and crystals of various types. To the ome, when the compounds used in the above method of obtaining, you are protecting group such as amino group, hydroxyl group or carboxyl group, these groups before the reaction may be protected by conventional protective groups, and these protective groups can be removed by methods well known per se, after the reaction.

When the compounds of the present invention are used as drugs, when necessary, they are mixed with adjuvants usually employed to produce compositions, such as excipient, a carrier and diluent. They can be administered orally or parenterally in such form, as a tablet, capsule, powder, syrup, granule, pill, suspension, emulsion, solution, powder preparations, suppositories, eye drops, nasal drops, ear drops, band-AIDS, ointment or injection. The method of administration, dose and time of injection it is possible to choose appropriately in accordance with the age, body weight and condition of the patient. Usually 0.01 to 1000 mg/kg / day you can enter the adult subject of oral or parenteral (e.g., injection, intravenous injection and the introduction of rectal part) once or in divided doses several times a day.

The usefulness of some representative compounds of the present invention are described in the following examples of tests.

The use of the test 1: test for inhibition of the production of MMP-13

6,8x103cells cell line SW1353 derived from cartilage of man, suspended in 100 μl of modified according to the method of Dulbecco environment, Needle, supplemented with 10% fetal bovine serum, were placed in 96-well plates and were cultured for 3 days. After replacing the culture medium with modified by way of Dulbecco Wednesday Needle containing 0.2% hydrolyzed milk albumin, and culturing the cells for 6 hours, was added compound and then added IL-1β to obtain a final concentration of 10 ng/ml after 1 hour. After 16 hours after stimulation, the supernatant was collected and the amount of MMP-13 in the culture supernatant was determined by ELISA kit (Amersham). The degree of inhibition was calculated from the amount of MMP-13 in the presence of the test compound, suggesting that the amount of MMP-13 was 100% in the absence of the test compound.

The results are shown in table 7.

Table 7
# exampleThe degree of inhibition (%) at 30 µmol/l
4
7
8
11
15
19
22
24
25
33
80
83
85
88
89
91
96
97
99
105
130
134
138
141
146
150
157
163
176
189
196
212
217
222
230
234
240
243
251
255
80
91
95
92
88
94
81
92
86
97
92
93
60
80
94
95
96
97
71
64
96
99
95
95
97
96
98
98
98
96
97
95
68
98
95
99
94
96
83
91
261
262
264
276
282
301
316
318
325
330
349
358
382
399
411
415
423
425
426
431
433
442
450
467
495
499
503
505
509
512
514
525
539
541
543
551
560
564
570
94
93
94
86
75
80
96
95
91
68
95
99
98
79
81
97
98
99
98
98
98
99
98
90
99
99
99
82
77
99
91
87
97
97
85
96
85
97
98

The test example 2: arthritis in mice induced by collagen type II

Used male mice DBA/1J age of eight weeks (Charles River Laboratories Japan Inc.). Added 4 mg/ml bovine collagen type II (Collagen Gijutsu Kenshukai)dissolved in 0.01 mol/l aqueous solution of acetic acid, and an equal number of complete adjuvant's adjuvant (Chondorex)containing 1 mg/ml of killed tubercle bacilli, obtaining emulsion and 0.1 ml of its percutaneous were injected with the base of the tail. Similar processing was performed for 21 days to induce arthritis. The test compound suspended in 0.5% aqueous solution of methyl cellulose and 30 mg/kg oral suspension was administered once daily from day 21 to day 35. In the control group in the same way introduced a 0.5%aqueous solution of methylcellulose. The severity of arthritis was evaluated in points: if the zero point for the animal without changes; one point for the animal with swelling in one or two joints of the fingers or weak swelling of the carpal or tarsal joint; two points for an animal with severe swelling in the carpal or tarsal joint or swelling in three or more joints of the fingers; three points for an animal with severe swelling along the front legs or back legs and, therefore, if the maximum of four limbs arthritis was estimated as 12 points. The degree of destruction of the bones was determined by x-ray four limbs on day 36, watching interphalangeal joints of the second through the fifth finger metacarpophalangeal and metatarsophalangeal joints from the first to the fifth finger, wrist or tarsal joint, heel bone, evaluating from 0 to 0.5 points the absence or presence of osteoporotic image in the joint and its vicinity, 0 points for a picture of a bone without changes, one point for the image partially destroyed bone and 2 points for the image completely destroyed bone and, thus, earning 105 points as a maximum for four limbs as counting the destruction of bones. The degree of inhibition was determined by the following formula.

The degree of inhibition (%) = 100 - (counting for the group treated with tested and is subject to connection/count for the control group)X100.

The connection specified in example 25, showed inhibitory effect of arthritis and the destruction of bones.

[Example]

Below the present invention is described by way of reference examples and examples, but the present invention is not limited to them.

The ratio of solvents when mixing them in eluent is a volume ratio. Unless otherwise noted, the media column chromatography on silica gel is silica gel B.W., BW-127ZH, manufactured by Fuji Silysia Chemical Ltd., and the media column chromatography on silica gel reversed-phase ODS is-AM12S05-2520WT of YMC Co., Ltd.

Each of the symbols used in each example has the following value.

AC: acetyl; BOC: tert-butoxycarbonyl,tBu: tert-butyl, Bz: benzoyl; Et: ethyl, Me: methyl, DMSO-d6: deuterated dimethyl sulfoxide.

Reference example 1

To a solution containing 4.0 g of 4-bromo-2-nitrobenzoic acid in 40 ml of acetone at room temperature add 3.4 potassium carbonate and 2.3 ml of dimethylsulfate, and the mixture was stirred at 50°C for 1 hour. After cooling the reaction mixture to room temperature the solvent is evaporated under reduced pressure. To the resulting residue is added water and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate consequently after the first washing with a saturated aqueous solution of sodium bicarbonate, hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure, thus obtaining 4.1 g of methyl 4-bromo-2-nitrobenzoate as a white solid.

1H-NMR (CDCl3) δ: of 3.97 (3H, s), a 7.85 (1H, d, J = 8,3 Hz), 8,07 (1H, DD, J = 8,3, 2.0 Hz), of 8.47 (1H, d, J = 2.0 Hz).

Reference example 2

To a solution containing 5.0 g of 4-bromo-2-nitrobenzoic acid in 50 ml of N,N-dimethylacetamide, add at room temperature 41 g of potassium carbonate, 4.6 g of the chloride of benzyltriethylammonium and 69 ml of 2-bromo-2-methylpropane and the mixture was stirred at 55°C for 10 hours. After cooling the reaction mixture to room temperature, add 12 ml of 2-bromo-2-methylpropane and the mixture was stirred at 55°C for 4 hours. After cooling the reaction mixture to room temperature, add water and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added methanol, and a solid substance was separated by filtration, thus obtaining 3.0 g of tert-butyl 4-bromo-2-nitrobenzoate as a white solid.

1H-NMR (CDCl3) δ: ,55 (9H, C), 7,63 (1H, d, J = 8,3 Hz), to 7.77 (1H, DD, J = 8,3, 1.9 Hz), 7,95 (1H, d, J = 1.9 Hz).

Reference example 3

2.6 g of iron powder are added to a solution containing 4,0 methyl-4-bromo-2-nitrobenzoate in a mixture of 20 ml methanol and 20 ml of acetic acid, and the resulting mixture is refluxed for 3 hours. After cooling the reaction mixture to room temperature, add saturated aqueous solution of sodium bicarbonate and ethyl acetate and insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and the solid is separated by filtration, thus obtaining 2.0 g of methyl 2-amino-4-bromobenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: the 3.89 (3H, s), 4,20 (2H, s), 7,26 (1H, DD, J = 8,3, 2,1 Hz), the 7.43 (1H, d, J = 2.1 Hz), 7,47 (1H, d, J = 8,3 Hz).

Reference example 4

3.0 g of iron powder are added to a solution containing 5.5 g of tert-butyl 4-bromo-2-nitrobenzoate in a mixture of 28 ml of methanol and 28 ml of acetic acid, and the resulting mixture is refluxed for 1 hour. After cooling reacts the Onna mixture to room temperature, add saturated aqueous solution of sodium bicarbonate and ethyl acetate and insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure, thus obtaining 4.3 g of tert-butyl 2-amino-4-bromobenzoate in the form of a pale yellow oil.

1H-NMR (DMSO-d6) δ: of 1.52 (9H, s), of 6.65 (1H, DD, J = 8,5, 2.0 Hz), 6,78 (2H, s), 6,98 (1H, d, J = 2.0 Hz), 7,55 (1H, d, J = 8,5 Hz).

Reference example 5

0,55 ml of benzoyl chloride are added to a solution containing 1.0 g of methyl 2-amino-4-bromobenzoate and 0.73 ml of triethylamine in 10 l of methylene chloride under ice cooling, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and to the residue is added saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining 0.9 g of methyl 2-(benzamido)-4-bromobenzoate in the form of a white solid.

1H-NMR (DMSO- 6) δ: 3,88 (3H, s), 7,54-7,58 (2H, m), to 7.61-7,66 (1H, m), to 7.77 (1H, DD, J = a 8.4 and 2.2 Hz), of 7.90 (1H, d, J = 8,4 Hz), 8,00-8,02 (2H, m)to 8.14 (1H, d, J = 2.2 Hz), 10,18 (1H, s).

Reference example 6

1.9 ml of benzoyl chloride are added to a solution containing 4,2 tert-butyl-2-amino-4-bromobenzoate and 2.6 ml of triethylamine in 42 ml of methylene chloride under ice cooling, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and to the residue is added water and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining 4.4 g of tert-butyl 2-(benzamido)-4-bromobenzoate in the form of a white solid.

1H-NMR (DMSO-d6) δ: of 1.55 (9H, s), 7,45 (1H, DD, J = 8,5, and 2.1 Hz), 7,60-of 7.69 (3H, m), 7,89 (1H, d, J = 8.5 Hz), 7.95 is-of 7.97 (2H, m), 8,78 (1H, d, J = 2.1 Hz), 11,68 (1H, s).

Reference example 7

To a solution containing 5.2 g of methyl 4-bromo-2-nitrobenzoate in a mixture of 42 ml of toluene, 16 ml of ethanol and 7.8 ml of water successively added 2.9 g of dihydroxyphenylalanine and 4.2 g of sodium bicarbonate and 1.1 g of tetrakis(triphenylphosphine is)palladium(0), and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, to the reaction mixture of 1.1 g of tetrakis(triphenylphosphine)palladium(0) and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, to the reaction mixture of 1.1 g of tetrakis(triphenylphosphine)palladium(0) and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, add water. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 20:1], while receiving 4.8 g of methyl-2-nitro-4-phenylbenzoate in the form of a pale yellow oil.

1H-NMR (CDCl3) δ: of 3.94 (3H, s), 7,44-7,53 (3H, m), 7,60-7,63 (2H, m), a 7.85-7,86 (2H, m), 8,07 (1H, d, J = 1.4 Hz).

Reference example 8

3.1 g of iron powder are added to a solution containing 4.8 g of methyl-2-nitro-4-phenylbenzoate in a mixture of 24 ml of methanol and 4 ml of acetic acid, and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and to the filtrate is added a saturated aqueous solution of sodium bicarbonate and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane, and the solid is separated by filtration, thus obtaining 1.8 g of methyl 2-amino-4-phenylbenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: the 3.89 (3H, s), 5,79 (2H, s), 6.87 in-6,91 (2H, m), 7,35-7,45 (3H, m), EUR 7.57-to 7.61 (2H, m), 7,92 (1H, d, J = 8.0 Hz).

Reference example 9

2,1 ml of benzoyl chloride are added to a solution containing 3.5 g of 5-iodine-2-methylaniline and 2.5 ml of triethylamine in 70 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture of hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium bicarbonate, and the solvent is evaporated p. and reduced pressure. To the obtained residue, add diisopropyl ether and hexane, and the solid is separated by filtration, thus obtaining of 4.2 g of N-(5-iodine-2-were)benzamide as a pale yellow solid.

1H-NMR (CDCl3) δ: to 2.29 (3H, s), of 6.96 (1H, d, J = 8.0 Hz), 7,44 (1H, DD, J = 1,6, 8.0 Hz), 7,49-7,63 (4H, m), 7,86-7,88 (2H, m), 8,39 (1H, d, J = 1.6 Hz).

Reference example 10

2.4 g of potassium permanganate and 1.8 g of anhydrous magnesium sulfate is added to the suspension containing of 4.2 g of N-(5-iodine-2-were)benzamide in 40 ml of tert-butyl alcohol and 80 ml of water at room temperature, and the resulting mixture is refluxed for 4 hours. After cooling the reaction mixture to room temperature, add 2.0 g of potassium permanganate and 1.5 g of anhydrous magnesium sulfate and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add 2.0 g of potassium permanganate and 1.5 g of anhydrous magnesium sulfate and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add 20 ml of ethanol and the insoluble matter is removed by filtration. The solvent is evaporated under reduced pressure, and add hydrochloric acid with a concentration of 1.0 mol/l and ethyl acetate. About the organic layer is separated and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. To the obtained residue, add diisopropyl ether and hexane and the solid is separated by filtration, thus obtaining a 3.3 g of 2-(benzamido)-4-iodobenzoyl acid as a pale yellow solid.

1H-NMR (DMSO-d6) δ: 7,58-of 7.69 (4H, m), 7,79 (1H, d, J = 8,3 Hz), 7,94-of 7.96 (2H, m), 9,17 (1H, d, J = 1.7 Hz), 12,17 (1H, s).

Reference example 11

of 0.62 g of potassium carbonate and 0.43 ml of dimethylsulfate added to a solution containing 1.5 g of 2-(benzamido)-4-iodobenzoyl acid in 15 ml of N,N-dimethylformamide, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 5:1], thus obtaining 1.3 g of methyl 2-(benzamido)-4-iodobenzoate in the form of a white solid.

1H-NMR (DMSO-d6) δ: the 3.89 (3H, s), to 7.59-of 7.69 (4H, m), of 7.75 (1H, d, J = 8,3 Hz), 7.95 is-7,98 (2H, m), 9,04 (1H, d, J = 1.5 Hz), to 11.61 (1H, s).

Reference example 12

To a solution containing 6.0 g of tert-butyl 4-bromo-2-nitrobenzoate in 48 ml of N,N-dimethylacetamide, after avatele added to 2.7 ml of styrene, 2.5 g of sodium acetate, 3.2 g of tetrabutylammonium bromide and 0.22 g of palladium (II) acetate and the mixture is heated and stirred in a nitrogen atmosphere at 90°C for 3 hours. After cooling the reaction mixture to room temperature, add 0.45 ml of styrene and 0.22 g of palladium(II) acetate and the mixture is heated and stirred at 110°C for 3 hours. After cooling the reaction mixture to room temperature, add water and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 20:1], thus obtaining 3.8 g of tert-butyl-2-nitro-4-((E)-2-phenylphenyl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: rate of 1.51 (9H, s), 7,32 was 7.45 (4H, m), to 7.59 (1H, d, J = 16.6 Hz), 7,66 (2H, d, J = 7,4 Hz), to 7.84 (1H, d, J = 8.1 Hz), 7,98 (1H, DD, J = 8,1, 1.5 Hz), 8,23 (1H, d, J = 1.5 Hz).

Reference example 13

0.74 g of 5% palladium on coal are added to a solution containing 3.7 g of tert-butyl-2-nitro-4-((E)-2-phenylphenyl)benzoate in a mixture of 56 ml of methanol and 56 ml of ethyl acetate, and the mixture is stirred under nitrogen atmosphere at room temperature for 2 hours. Insoluble substances are removed Phi is trevanian, and the solvent is evaporated under reduced pressure, thus obtaining 3.4 g of tert-butyl 2-amino-4-penicillinate in the form of a white solid.

1H-NMR (CDCl3) δ: was 1.58 (9H, s), and 2.79-2.91 in (4H, m), 5,63 (2H, s), 6,44-of 6.49 (2H, m), 7,17-7,21 (3H, m), 7,26-7,30 (2H, m), 7,72 (1H, d, J = 8,4 Hz).

Reference example 14

19 mg of palladium (II) acetate are added to a solution containing 0.50 g of tert-butyl 4-bromo-2-nitrobenzoate, 50 mg of tri-(o-tolyl)phosphine, of 0.44 ml allylbenzene and 0.46 ml of triethylamine in 5 ml of toluene, and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, add 20 mg of palladium acetate (II) and the resulting mixture is refluxed for 7 hours. After cooling the reaction mixture to room temperature, the insoluble portion removed by filtration and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 30:1], while receiving 0.31 g of tert-butyl-2-nitro-4-(3-phenyl-1-propenyl)benzoate.

62 mg of 5% palladium on coal are added to a solution containing 0.31 g of tert-butyl-2-nitro-4-(3-phenyl-1-propenyl)benzoate in 3 ml of ethyl acetate at room temperature, and the mixture is stirred in hydrogen atmosphere at the same temperature out within 5 hours and 30 minutes. The insoluble portion removed by filtration and the solvent is evaporated under reduced pressure, to thereby obtain 0.31 g of tert-butyl 2-amino-4-(3-phenylpropyl)benzoate as a yellow oil.

1H-NMR (CDCl3) δ: 1.57 in (9H, s), 1,88-of 1.97 (2H, m)to 2.55 (2H, t, J = 7,6 Hz), 2,63 (2H, t, J = 7,6 Hz), 5,64 (2H, s), 6,44-6,48 (2H, m), 7,16-7,21 (3H, m), 7,26-7,30 (2H, m), 7,72 (1H, d, J = 8.0 Hz).

Reference example 15

19 mg of palladium (II) acetate are added to a solution containing 0.50 g of tert-butyl 4-bromo-2-nitrobenzoate, 50 mg of tri-(o-tolyl)phosphine, and 0.50 ml of 4-phenyl-1-butene and 0.46 ml of triethylamine in 5 ml of toluene, and the resulting mixture is refluxed under nitrogen atmosphere for 4 hours and 30 minutes. After cooling the reaction mixture to room temperature, add 20 mg of palladium (II) acetate and the resulting mixture is refluxed for 5 hours and 30 minutes. After cooling to room temperature the reaction mixture was purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 30:1], while receiving 0.35 g of tert-butyl-2-nitro-4-(4-phenyl-1-butenyl)benzoate.

70 mg of 5% palladium on coal are added to a solution containing 0.35 g of tert-butyl-2-nitro-4-(4-phenyl-1-butenyl)benzoate in 4 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 8 hours. The insoluble portion removed by filtration,and the solvent is evaporated under reduced pressure, while receiving 0.40 g of tert-butyl 2-amino-4-(4-phenylbutyl)benzoate as a yellow oil.

1H-NMR (CDCl3) δ: 1.57 in (9H, s), 1,61-to 1.67 (4H, m), 2,50-of 2.54 (2H, m), 2,60-2,63 (2H, m), 5,63 (2H, s), 6.42 per-6,47 (2H, m), 7,15-7,19 (3H, m), 7,25-7,29 (2H, m), of 7.70 (1H, d, J = 8.0 Hz).

Reference example 16

of 0.54 g of tetrakis(triphenylphosphine)palladium(0) are added to a solution containing 3.5 g of tert-butyl 2-(benzamido)-4-bromobenzoate and 5.0 g tributyltinhydride in 35 ml of toluene, and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 20:1], while receiving 1.4 g of tert-butyl 2-(benzamido)-4-vinylbenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: 1,63 (9H, s), 5,42 (1H, d, J = 11,0 Hz), 5,95 (1H, d, J = 17,7 Hz), 6,77 (1H, DD, J = 17.7 and, of 11.0 Hz), to 7.15 (1H, DD, J = 8,2) and 1.7 Hz), 7,50-of 7.60 (3H, m), of 7.97 (1H, d, J = 8,2 Hz), 8,05-8,10 (2H, m), 9,01 (1H, d, J = the 1.7 Hz), 12,23 (1H, s).

Reference example 17

of 0.67 ml of triethylamine and 0.34 ml of benzoyl chloride are added to a solution containing 0.51 g of 3-amino-4-methylbenzophenone in 5 ml of methylene chloride under ice cooling, and the mixture is stirred at room temperature is 2 hours. The solvent of the reaction mixture is evaporated under reduced pressure, and add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining 0.71 g of N-(5-benzoyl-2-were)benzamide as a white solid.

1H-NMR (CDCl3) δ: 2,43 (3H, s), 7,37 (1H, d, J = 7.8 Hz), 7,47-7,52 (4H, m), 7,56-7,63 (3H, m), 7,74 (1H, s), 7,82-7,86 (2H, m), 7,87-to $ 7.91 (2H, m), 8,29 (1H, s).

Reference example 18

2,7 ml of (trimethylsilyl)acetylene are added to a solution containing 3.2 g of methyl 2-(benzamido)-4-bromobenzoate, 92 mg of copper iodide (I), 0.34 g of bis(triphenylphosphine)palladium(II)chloride and 2.7 ml of triethylamine in 30 ml of toluene, at room temperature, and the mixture is stirred in nitrogen atmosphere at 70-80°C for 2 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/l and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous sulfate is magnesium after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining 3.5 g of methyl 2-(benzamido)-4-(2-trimethylsilyl)ethinyl)benzoate as a pale yellow solid.

of 0.68 g of potassium carbonate are added to a solution containing 3.5 g of methyl 2-(benzamido)-4-(2-(trimethylsilyl)ethinyl)benzoate in 17 ml of methanol and 17 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure, and add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/l, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing hydrochloric acid with a concentration of 1.0 mol/l, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 8:1], thus obtaining 1.6 g of methyl 2-(benzamido)-4-ethynylbenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: 3,25 (1H, s), of 3.97 (3H, s), 7,22 (1H, DD, J = 8,3, 1.5 Hz), 7,51-7,58 (3H, m), 8,02-of 8.06 (3H, m), 9,12 (1H, d, J = 1.5 Hz), 12,02 (1H, s).

Reference example 19

of 4.2 g of iron powder are added to a solution containing 5.7 g of 1-methyl-2-nitro-4-fenxian the Ola in 57 ml of methanol and 17 ml of acetic acid, and the resulting mixture is refluxed for 5 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and saturated aqueous sodium hydrogen carbonate solution and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is dissolved in 60 ml of diethyl ether, and added to 2.1 ml of hydrochloric acid with ice cooling. The solid is separated by filtration, to thereby obtain 4.7 g of the hydrochloride of 2-methyl-3-phenoxyimino in the form of a white solid.

1H-NMR (DMSO-d6) δ: of 2.27 (3H, s), PC 6.82 (1H, DD, J = 8,3, 2.4 Hz), of 6.96 (1H, d, J = 2.4 Hz), 7,03 (2H, d, J = 7.5 Hz), 7,17 (1H, t, J = 7.5 Hz), 7,26 (1H, d, J = 8,3 Hz), 7,39-the 7.43 (2H, m).

Reference example 20

To a solution containing 0.50 g of the hydrochloride of 2-methyl-5-phenoxyimino in 5 ml of N,N-dimethylformamide, successively added of 0.91 ml of triethylamine and 0.27 ml of benzoyl chloride under ice cooling, and the mixture is stirred at room temperature for 3 hours. To the reaction mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. the content of inorganic fillers layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining at 0.42 g of N-(2-methyl-5-phenoxyphenyl)benzamide in the form of a white solid.

1H-NMR (CDCl3) δ: 2,31 (3H, s), is 6.78 (1H, DD, J = 8,3, 2.4 Hz), 7,03 (2H, d, J = 7.8 Hz), was 7.08 (1H, t, J = 7.5 Hz), 7,17 (1H, d, J = 8,3 Hz), 7,30-7,34 (2H, m), 7,47-7,51 (2H, m), 7,54-7,58 (1H, m), to 7.67 (1H, s), 7,78 (1H, s), 7,86 (2H, d, J = 7,1 Hz).

Reference example 21

to 9.9 g of potassium carbonate, of 0.82 g of the chloride of benzyltriethylammonium and 21 ml of 2-bromo-2-methylpropane added to a solution containing 0.93 g of 2-nitro-4-phenoxybenzoic acid in 14 ml of N,N-dimethylacetamide at room temperature, and the mixture was stirred at 55°C for 18 hours. After cooling the reaction mixture to room temperature, add water and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate, 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure, thus obtaining 0,86 g of tert-butyl-2-nitro-4-phenoxybenzoate in the form of a white solid.

1/sup> H-NMR (DMSO-d6) δ: to 1.48 (9H, s), 7.18 in-of 7.23 (2H, m), 7,26-to 7.32 (2H, m), 7,47-7,53 (2H, m), 7,54 (1H, d, J = 2.4 Hz), the 7.85 (1H, d, J = 8,5 Hz).

Reference example 22

0.17 g of 5% palladium on coal are added to a solution containing 0,82 g of tert-butyl-2-nitro-4-phenoxybenzoate in a mixture of 8 ml of methanol and 8 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 4 hours and 30 minutes. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 10:1], while receiving 0,63 g of tert-butyl 2-amino-4-phenoxybenzoate in the form of a colorless oil.

1H-NMR (CDCl3) δ: 1.57 in (9H, s), 6,16 (1H, d, J=2.3 Hz), 6,27 (1H, DD, J=9,0, 2.3 Hz),? 7.04 baby mortality-7,06 (2H, m), 7,14-to 7.18 (1H, m), 7,34-7,38 (2H, m), 7,78 (1H, d, J=9.0 Hz).

Reference example 23

3.1 ml of triethylamine and 1.3 ml of benzoyl chloride are added to a solution containing 1.9 g of methyl 2-amino-4-methoxybenzoate in 19 ml of methylene chloride under ice cooling, and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure and the obtained residue is added chloroform and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing PEFC is therefore saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the resulting solution was added hexane and diisopropyl ether and the solid is separated by filtration, thus obtaining 2.6 g of methyl 2-(benzamido)-4-methoxybenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: to 3.92 (3H, s), 3,93 (3H, s), of 6.65 (1H, DD, J=9,0, 2.7 Hz), 7,51-to 7.59 (3H, m), of 8.00 (1H, d, J=9.0 Hz), 8,05-8,07 (2H, m), 8,63 (1H, d, J=2.7 Hz).

Reference example 24

0,94 g of aluminium chloride are added to a solution containing of 0.67 g of methyl 2-(benzamido)-4-methoxybenzoate in 7 ml of toluene, at room temperature, and the mixture is stirred at 80°C for 2 hours and 30 minutes. After cooling the reaction mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/l, and the solid is separated by filtration, thus obtaining a 0.23 g of methyl 2-(benzamido)-4-hydroxybenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: 3,93 (3H, s), of 6.68 (1H, DD, J=8,9 and 2.5 Hz), 7,54 to 7.62 (3H, m), 8,02-with 8.05 (3H, m), 8,84 (1H, d, J=2.5 Hz), of 9.30-9,40 (1H, usher.), 12,46 (1H, s).

Reference example 25

0.50 g of potassium carbonate and 0.50 g of methyl-4-(methyl bromide)-2-nitrobenzoate are added to a solution containing 0.18 g of phenol in 5 ml of N,N-dimethylformamide, at room temperature, and the mixture was stirred at the same temperature for 10 hours. To the reaction the mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate

= 6:1], while receiving of 0.53 g of methyl-2-nitro-4-(phenoxymethyl)benzoate as a colourless oil.

1H-NMR (CDCl3) δ: 3,93 (3H, s)to 5.17 (2H, s), 6,95-7,03 (3H, m), 7,30-7,34 (2H, m), 7,72-7,79 (2H, m), 7,95-8,00 (1H, m).

Reference example 26

1.01 g of potassium carbonate and 0.39 ml of thiophenol added to a solution containing 1,00 g methyl-4-(methyl bromide)-2-nitrobenzoate in 10 ml of N,N-dimethylformamide, at room temperature, and the mixture was stirred at the same temperature for 7 hours. To the reaction mixture are added ethyl acetate, and the insoluble matter is removed by filtration and add water. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 4:1], while receiving 0,70 g of methyl-2-nitro-4-((phenylthio)methyl)benzoate as a pale yellow oil.

1 H-NMR (CDCl3) δ: 3,86 (3H, s), 4,27 (2H, s), 6,60-6,74 (5H, m), 7,15-7,19 (2H, m), 7,82 (1H, d, J = 8,3 Hz).

Reference example 27

0.39 g of iron powder are added to a solution containing 0,70 g of methyl-2-nitro-4-((phenylthio)methyl)benzoate in a mixture of 7 ml of methanol and 2.1 ml of acetic acid, and the resulting mixture is refluxed for 3 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and saturated aqueous sodium hydrogen carbonate solution, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is dissolved in 10 ml of diethyl ether, and add 1.2 ml of a solution of 1.9 mol/l hydrogen chloride/ethyl acetate under ice cooling, and the solid is separated by filtration, to thereby obtain 0.39 g of the hydrochloride of methyl 2-amino-4-((phenylthio)methyl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: 3,76 (3H, s), of 4.13 (2H, s), 4,30-4,70 (2H, usher.), 6,55 (1H, DD, J = 8,2) and 1.7 Hz), 6,79 (1H, d, 1.7 Hz), 7,15-7,19 (1H, m), 7,26-7,33 (4H, m), a 7.62 (1H, d, J = 8,2 Hz).

Reference example 28

The following connection get that the e way, as in referential example 2.

tert-Butyl-4-chloro-2-nitrobenzoate

1H-NMR (CDCl3) δ: of 1.55 (9H, s), to 7.59 to 7.62 (1H, m), 7,70-7,73 (1H, m), 7,79 (1H, d, J = 2.0 Hz).

Reference example 29

The following connection receive the same manner as in reference example 2.

tert-Butyl 2-(benzamido)-4-iodobenzoate

1H-NMR (CDCl3) δ: of 1.62 (9H, s), 7,45 (1H, DD, J = 8,5) and 1.7 Hz), 7,51-of 7.60 (3H, m), 7,68 (1H, d, J = 8.5 Hz), 8,02-8,07 (2H, m), 9,38 (1H, d, J = 1.7 Hz), 12,13-12,20 (1H, usher.).

Reference example 30

To a solution containing 2.0 g of tert-butyl 4-bromo-2-nitrobenzoate in 20 ml of toluene, successively added to 6.0 ml of ethanol, 3.0 ml of water, 1.2 g of 3-Chlorfenvinphos acid, 1.7 g of sodium carbonate and 0.23 g of tetrakis(triphenylphosphine)palladium(0) and the resulting mixture is refluxed under nitrogen atmosphere for 3 hours. After cooling the reaction mixture to room temperature, add water. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 10:1], while receiving 0,70 g of tert-butyl 4-(3-chlorophenyl)-2-nitrobenzoate as a white solid ve is esta.

1H-NMR (DMSO-d6) δ: of 1.52 (9H, s), 7,53-to 7.59 (2H, m), to 7.77-of 7.82 (1H, m), 7,89-of 7.95 (2H, m), 8,15 (1H, DD, J = 8,1, 1,6 Hz), a 8.34 (1H, d, J = 1.6 Hz).

Reference example 31

The following connection receive the same manner as in reference example 30.

tert-Butyl 4-(4-(tert-butoxycarbonyl)oxyphenyl)-2-nitrobenzoate

1H-NMR (DMSO-d6) δ: rate of 1.51 (9H, s), of 1.52 (9H, s), of 7.36 (2H, d, J = 8,8 Hz), 7,87 (2H, d, J = 8,8 Hz), to $ 7.91 (1H, d, J = 8.1 Hz), 8,11 (1H, DD, J = 8,1, 1.8 Hz), 8,29 (1H, d, J = 1,8 Hz).

Reference example 32

To a solution containing 1.5 g of tert-butyl-4-chloro-2-nitrobenzoate in 15 ml of toluene, successively added 1.1 g of 2,4-diftorhinolonom acid, 2.8 g of cesium carbonate, 27 mg of palladium acetate and 25 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, and the resulting mixture is refluxed under nitrogen atmosphere for 8 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is e substance separated by filtration, while receiving 0.95 g of tert-butyl 4-(2,4-differenl)-2-nitrobenzoate as a white solid.

1H-NMR (DMSO-d6) δ: of 1.52 (9H, s), 7,26-7,31 (1H, m), 7,44-7,51 (1H, m), 7,72-7,79 (1H, m), to 7.93 (1H, d, J = 7.9 Hz), 7,98 (1H, d, J = 7.9 Hz), 8,17 (1H, s).

Reference example 33

The following connection receive the same manner as in reference example 32.

tert-Butyl 4-(benzo[1,3]dioxol-5-yl)-2-nitrobenzoate

1H-NMR (DMSO-d6) δ: rate of 1.51 (9H, s), 6,11 (2H, s), 7,06 (1H, d, J = 8.1 Hz), 7,34 (1H, DD, J = 8,1, 1.9 Hz), was 7.45 (1H, d, J = 1.9 Hz), the 7.85 (1H, d, J = 8.1 Hz), of 8.04 (1H, DD, J = 8,1, 1.9 Hz), to 8.20 (1H, d, J = 1.9 Hz).

Reference example 34

The following connection receive the same manner as in reference example 30.

tert-Butyl 4-(benzofuran-2-yl)-2-nitrobenzoate

1H-NMR (DMSO-d6) δ: 1,53 (9H, s), 7,30 and 7.36 (1H, m), 7,40 was 7.45 (1H, m), 7.68 per-7,76 (1H, m), of 7.75 (1H, d, J = 7,3 Hz), 7,82 (1H, d, J = 0.7 Hz), of 7.96 (1H, d, J = 8.1 Hz), 8,29 (1H, DD, J = 8,1, 1,6 Hz), 8,49 (1H, d, J = 1.6 Hz).

Reference example 35

0.33 g of 10% palladium on coal are added to a solution containing 1.1 g of tert-butyl 4-(3-chlorophenyl)-2-nitrobenzoate in a mixture of 11 ml of methanol and 11 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 3 hours. After removing insoluble substances by filtration, the solvent is evaporated under reduced pressure. To the resulting stackedinline add 11 ml of acetic acid, 11 ml of methanol and 0.33 g of 10% palladium on charcoal, and the mixture is stirred in hydrogen atmosphere at room temperature for 2 hours. After removing insoluble substances by filtration, the solvent is evaporated under reduced pressure, thus obtaining 0,70 g of tert-butyl 2-amino-4-(3-chlorophenyl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: of 1.55 (9H, s), 6,63-6,69 (2H, usher.), 6,83 (1H, DD, J = 8,5, 1.9 Hz), 7,06 (1H, d, J = 1.9 Hz), 7,46 (1H, dt, J = 7,8, and 1.6 Hz), to 7.50 (1H, t, J = 7.8 Hz), EUR 7.57 (1H, dt, J = 7,8, and 1.6 Hz), 7,63 (1H, t, J = 1.6 Hz), 7,73 (1H, d, J = 8,5 Hz).

Reference example 36

The following connection receive the same manner as in reference example 35.

tert-Butyl 2-amino-4-(4-((tert-butoxycarbonyl)oxy)phenyl)benzoate

1H-NMR (DMSO-d6) δ: rate of 1.51 (9H, s), 1.55V (N, C), 6,66-6,70 (2H, usher.), to 6.80 (1H, DD, J = 8,5, 1.8 Hz), 7,02 (1H, d, J = 1,8 Hz), 7,27-to 7.32 (2H, m), to 7.61-the 7.65 (2H, m), 7,73 (1H, d, J = 8,5 Hz).

Reference example 37

0.27 g of 10% palladium on coal are added to a solution containing about 0.90 g of tert-butyl 4-(2,4-differenl)-2-nitrobenzoate in a mixture of 9.0 ml of methanol and 9.0 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 30 minutes. After removing insoluble substances by filtration, the solvent is evaporated under reduced pressure, thus obtaining 0,80 g of tert-butyl 2-amino-4-(2,4-differenl)benzoe is in the form of a white solid.

1H-NMR (DMSO-d6) δ: of 1.55 (9H, s), of 6.65 (1H, d, J = 8,3 Hz), 6,66-of 6.73 (2H, usher.), 6,91 (1H, s), 7,17-7,22 (1H, m), 7,33-7,39 (1H, m), 7,50-7,56 (1H, m), 7,72 (1H, d, J = 8,3 Hz).

Reference example 38

0,42 g 10% palladium on coal are added to a solution containing 1.4 g of tert-butyl 4-(benzo[1,3]dioxol-5-yl)-2-nitrobenzoate in a mixture of 14 ml of methanol and 14 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 2 hours. After removing insoluble substances by filtration, the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 20:1], while receiving 0.52 g of tert-butyl 2-amino-4-(benzo[1,3]dioxol-5-yl)benzoate as a pale yellow solid.

1H-NMR (DMSO-d6) δ: and 1.54 (9H, s), 6,07 (2H, s), 6,57-of 6.65 (2H, usher.), to 6.75 (1H, d, J = 8.5 Hz), of 6.96 (1H, s), 7,00 (1H, d, J = 8.6 Hz), 7,10 (1H, d, J = 8.6 Hz), to 7.15 (1H, s), to 7.68 (1H, d, J = 8,5 Hz).

Reference example 39

0,69 g of iron powder are added to a suspension containing 1.4 g of tert-butyl 4-(benzofuran-2-yl)-2-nitrobenzoate in a mixture of 7.0 ml of methanol and 7.0 ml of acetic acid, and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature the solvent is evaporated at igenom pressure. To the obtained residue is added saturated aqueous sodium hydrogen carbonate solution and ethyl acetate and the insoluble portion removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. Hexane is added to the obtained residue and a solid substance was separated by filtration, thus obtaining 0.88 g of tert-butyl 2-amino-4-(benzofuran-2-yl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: of 1.56 (9H, s), 6,76-6,84 (2H, usher.), 7,07 (1H, DD, J = 8,5, and 1.6 Hz), 7,26-7,39 (3H, m), the 7.43 (1H, s), to 7.64 (1H, d, J = 8.1 Hz), 7,69 (1H, d, J = 8.1 Hz), of 7.75 (1H, d, J = 8,5 Hz).

Reference example 40

To a solution containing 0.50 g of tert-butyl 4-bromo-2-nitrobenzoate in 5 ml of N,N-dimethylacetamide, add and 0.37 ml of 3-vigilante, of 0.47 ml of triethylamine and 0.11 g of palladium acetate at room temperature, and the mixture is stirred under nitrogen atmosphere at 110°C for 4 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and water. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 10:1], while receiving 0.20 g of tert-butyl 4-((E)-2-(3-methoxyphenyl)vinyl)-2-nitrobenzoate as a pale yellow solid.

1H-NMR (DMSO-d6) δ: rate of 1.51 (9H, s), 3,81 (3H, s), 6.90 to-6,94 (1H, m), 7,20-7,27 (2H, m), 7,34 (1H, t, J = 7.9 Hz), the 7.43 (1H, d, J = 16.6 Hz), 7,55 (1H, d, J = 16.6 Hz), to 7.84 (1H, d, J = 8.0 Hz), of 7.97 (1H, d, J = 7.8 Hz), 8,21 (1H, ).

Reference example 41

0,70 g of iron powder are added to a suspension containing 1.5 g of tert-butyl 4-((E)-2-(3-methoxyphenyl)vinyl)-2-nitrobenzoate in a mixture of 7.5 ml of methanol and 7.5 ml of acetic acid, and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature the solvent is evaporated under reduced pressure. To the obtained residue is added saturated aqueous sodium hydrogen carbonate solution and ethyl acetate, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (speeches the s) manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 4:1], while receiving of 0.44 g of tert-butyl 2-amino-4((E)-2-(3-methoxyphenyl)vinyl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: and 1.54 (9H, s), of 3.80 (3H, s), 6,57-of 6.65 (2H, usher.), 6,80-6,92 (3H, m), 7,15-of 7.23 (4H, m), 7,29 (1H, t, J = 8.1 Hz), to 7.64 (1H, d, J = 8,3 Hz).

Reference example 42

To a solution containing 4.0 g of tert-butyl 2-(benzamido)-4-bromobenzoate in 40 ml of dioxane, sequentially at room temperature is added 3.1 g of potassium acetate, 5.9 g of bis(pinacolato)diboron and 0.43 g of complex (1,1'-bis(diphenylphosphino)ferrocene)palladium(II)dichloride-dichloromethane; methylene chloride, and the resulting mixture is refluxed for 3 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 4:1], while receiving 3.6 g of tert-butyl 2-(benzamido)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: of 1.33 (12H, s), and 1.54 (9H, s)to 7.50 (1H, DD, J = 7,8, 1.0 Hz), 7,58-to 7.68 (3H, m), 7,92 (1H, d, J = 7.8 Hz), of 7.96-of 8.00 (2H, m), 8,72 (1H, d, J = 1.0 Hz), 11,43 (1H, s).

Reference example 43

20 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added to the solution, containing of 0.47 g of methyl 2-(1H-pyrrol-1-yl)pyridine-4-carboxylate in a mixture of 4.0 ml of methanol and 4.0 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture successively added 5.0 ml of hydrochloric acid concentration of 1.0 mol/l and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether, and the solid is removed by filtration, thus obtaining 0.39 g of 2-(1H-pyrrol-1-yl)pyridine-4-carboxylic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,32 (2H, t, J = 2.3 Hz), to 7.64 (1H, DD, J = 5,1, 1.3 Hz), 7,76 (2H, t, J = 2.3 Hz), 8,02 (1H, t, J = 0.9 Hz), at 8.60 (1H, DD, J = 5,1, 0.9 Hz), 13,70-13,95 (1H, usher.).

Example 1

0.56 g of 2-(tributylamine)thiazole and 0,090 g of tetrakis(triphenylphosphine)palladium(0) are added to a solution containing 0.50 g of methyl 2-(benzamido)-4-bromobenzoate in 5 ml of toluene, and the resulting mixture is refluxed under nitrogen atmosphere for 6 hours. After cooling the reaction mixture to room temperature the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate =3:1], while receiving 0.25 g of methyl 2-(benzamido)-4-(thiazol-2-yl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: 3,93 (3H, s), to 7.61-of 7.70 (3H, m), 7,82 (1H, DD, J = 8,5, 1.8 Hz), 7,95 (1H, d, J = 3.2 Hz), 7,99 shed 8.01 (2H, m), with 8.05 (1H, d, J = 3.2 Hz), 8,13 (1H, d, J = 8.5 Hz), 9,29 (1H, d, J = 1,8 Hz), 11,73 (1H, s).

Example 2

0,35 ml of 10% aqueous sodium hydroxide is added to the suspension containing 0.25 g of methyl 2-(benzamido)-4-(thiazol-2-yl)benzoate in 5 ml of ethanol, and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add hydrochloric acid with a concentration of 1.0 mol/l and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining a 0.23 g of 2-(benzamido)-4-(thiazol-2-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: to 7.61-of 7.70 (3H, m), 7,80 (1H, DD, J = 8,3) and 1.7 Hz), 7,94 (1H, d, J = 3.2 Hz), 7,98-of 8.00 (2H, m), with 8.05 (1H, d, J = 3.2 Hz), 8,17 (1H, d, J = 8,3 Hz), 9,43 (1H, d, J = 1.7 Hz), to 12.28 (1H, s).

Example 3

of 0.28 ml of benzoyl chloride are added to a solution containing 0.50 g of methyl 2-amino-4-phenylbenzoate and 0.36 ml of triethylamine in 10 ml of methylene chloride, and the mixture paramesh what happens at room temperature over night. The solvent is evaporated under reduced pressure, and add water and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether and the solid is separated by filtration, thus obtaining 0.52 g of methyl 2-(benzamido)-4-phenylbenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: 3,99 (3H, s), 7,37-of 7.60 (7H, m), 7,73 to 7.75 (2H, m), 8.07-a 8,10 (2H, m), 8,15 (1H, d, J = 8,3 Hz), 9,29 (1H, d, J = 1.7 Hz), 12,13 (1H, s).

Example 4

1.2 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added to the suspension containing 0.50 g of methyl 2-(benzamido)-4-phenylbenzoate in 5 ml of methanol and 2.5 ml of dioxane at room temperature, and the mixture was stirred at 50°C for 30 minutes. After cooling the reaction mixture to room temperature, add hydrochloric acid with a concentration of 1.0 mol/l to establish a pH of 3, and add water and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To the resulting ostadalova hexane, and the solid is separated by filtration, thus obtaining 0.36 g of 2-(benzamido)-4-vinylbenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,45-7,69 (7H, m), 7,73 to 7.75 (2H, m), 7,98-of 8.00 (2H, m), 8,15 (1H, d, J = 8.1 Hz), which is 9.09 (1H, d, J = 2.0 Hz), 12,29 (1H, s), 13,70-14,00 (1H, usher.).

Example 5

55 mg of pyridine-3-Bronevoy acid, 88 mg of sodium bicarbonate and 17 mg of tetrakis(triphenylphosphine)palladium(0) are added to a solution containing 100 mg of methyl 2-(benzamido)-4-bromobenzoate in a mixture of 2.0 ml of toluene, 0.5 ml of ethanol and 0.2 ml of water, and the mixture is refluxed for 2 hours. After the reaction mixture was cooled to room temperature, added 17 mg of tetrakis(triphenylphosphine)palladium(0) and the mixture refluxed for 2 hours. After cooling the reaction mixture to room temperature, add toluene and water. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 3.0 ml of ethanol and 0.5 ml of 2.0 mol/l aqueous sodium hydroxide, and the mixture is stirred at room temperature for 2 hours. The reaction mixture was purified column of chromatogr is via on silica gel with reversed phase [eluent: aqueous solution 30-100% acetonitrile/0.1% of triperoxonane acid], while receiving 25 mg trifenatate 2-(benzamido)-4-(pyridin-3-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,45-7,49 (2H, m), 7,56 (1H, t, J = 7.0 Hz), 7,63-of 7.69 (2H, m), to 7.77 (2H, d, J = 7,1 Hz), of 7.97 (1H, DD, J = 8,1 Hz, J = 1.2 Hz), of 8.09 (1H, s), 8,17 (1H, d, J = 7,6 Hz), 8,65 (1H, d, J = 5,1 Hz), 8,83 (1H, s), of 10.25 (1H, s).

Example 6

56 mg of 4-(acetamido)phenylboronic acid, 55 mg of sodium carbonate and 30 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 90°C for 11 hours. After cooling the reaction mixture to room temperature, add 19 mg of 4-(acetamido)phenylboronic acid and the mixture was stirred at 90°C for 12 hours. After cooling the reaction mixture to room temperature, add 11 mg of sodium carbonate and 30 mg deposited on the polymer bis(acetato)triphenylphosphine(II) and the mixture was stirred at 90°C for 14 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.2 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with hydrochloric acid conc is of 1.0 mol/l of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue was added 1 ml of aqueous sodium hydroxide with a concentration of 1.0 mol/l and 2 ml of ethanol and the mixture is stirred at room temperature for 1 hour. Add hydrochloric acid with a concentration of 0.6 mol/l, and a solid substance was separated by filtration and purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 40-100% acetonitrile/0.1% of triperoxonane acid], while receiving 5.9 mg of 4-(4-acetamido)phenyl)-2-(benzamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 2.08 (3H, s), 7,49-7,52 (1H, m), 7,60-7,76 (7H, m), to 7.99 (2H, d, J = 7,6 Hz), 8,11 (1H, d, J = 8.1 Hz), 9,06 (1H, d, J = 1.7 Hz), 10,14 (1H, s).

Example 7

The following connection receive the same manner as in example 6.

2-(Benzamido)-4-(thiophene-2-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,22 (1H, t, J = 4.5 Hz), 7,54-to 7.67 (5H, m), 7,71 (1H, d, J = 4.5 Hz), to 7.99 (2H, d, J = 6.8 Hz), 8,08 (1H, d, J = 8.6 Hz), 9,11 (1H, s).

Example 8

51 mg benzofuran-2-Bronevoy acid, 55 mg of sodium carbonate and 30 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 90°C for 22 hours. After cooling, actionnow mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.2 mol/L. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 1.0 ml of aqueous sodium hydroxide with a concentration of 1.0 mol/l and 2.0 ml of ethanol, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture of hydrochloric acid with a concentration of 0.6 mol/l, and the solid is separated by filtration, while receiving 11 mg of 2-(benzamido)-4-(benzofuran-2-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: to 7.32 (1H, TD, J = 7,3, 0.7 Hz), 7,40 (1H, TD, J = 7,7, 1.1 Hz), 7,62-7,79 (7H, m), 8,01-8,03 (2H, m), 8,16 (1H, d, J = 8.6 Hz), was 9.33 (1H, s).

Example 9

36 mg of 3-methoxyphenylacetic acid, 55 mg of sodium carbonate and 30 mg of precipitated polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 90°C for 11 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.2 mol/L. Organic layer separated Aut and dried over anhydrous magnesium sulfate after sequential washing with hydrochloric acid with a concentration of 1.0 mol/l, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 1.0 ml of aqueous sodium hydroxide with a concentration of 1.0 mol/l and 2.0 ml of ethanol and the mixture is stirred at room temperature for 1 hour. To the reaction mixture of hydrochloric acid with a concentration of 0.6 mol/l and the solid is separated by filtration, while receiving 18 mg of 2-(benzamido)-4-(3-methoxyphenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 3.85 (3H, s), 7,05 (1H, DD, J = 8,2, 2.6 Hz), 7,24 (1H, s), 7,30 (1H, d, J = 8.1 Hz), 7,47 (1H, t, J = 7.9 Hz), 7,53 (1H, DD, J = 8,3, 1.5 Hz), 7,60-of 7.69 (3H, m), to 7.99 (2H, d, J = 7,1 Hz), 8,13 (1H, d, J = 8,3 Hz), 9,06 (1H, s), 12,30 (1H, s).

Example 10

The following connection receive the same manner as in example 9.

2-(Benzamido)-4-(4-carboxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: EUR 7.57-of 7.69 (4H, m), 7,87 (2H, d, J = 8.0 Hz), 7,99 shed 8.01 (2H, m), 8,10 (2H, d, J = 8,3 Hz), 8,17 (1H, d, J = 8.6 Hz), 9,13 (1H, s).

Example 11

52 mg of 3,4-methylenedioxyphenylacetone acid, 55 mg of sodium carbonate and 30 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture peremeci is up at 90°C for 22 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.2 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 1.0 ml of aqueous sodium hydroxide with a concentration of 1.0 mol/l and 2.0 ml of ethanol, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture of hydrochloric acid with a concentration of 0.6 mol/l, and the solid is separated by filtration, to thereby obtain 43 mg of 2-(benzamido)-4-(benzo[1,3]dioxol-5-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,11 (2H, s), was 7.08 (1H, d, J = 8.1 Hz), 7,24 (1H, DD, J = 8,2, 1.8 Hz), 7,30 (1H, d, J = 1.7 Hz), 7,45-7,47 (1H, m), to 7.59-of 7.69 (3H, m), 7,98-of 8.00 (2H, m), of 8.09 (1H, d, J = 8.1 Hz), 9,01 (1H, s).

Examples 12, 13

Compounds shown in table 8, receive the same manner as in example 11.

Table 8
Example No. R3
12
13

2-(Benzamido)-4-(1H-indol-5-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,56 (1H, s), the 7.43 (1H, t, J = 2.7 Hz), 7,47-of 7.69 (6H, m), 7,94 (1H, s), 8,01 (2H, d, J = 7,1 Hz)to 8.12 (1H, d, J = 8,3 Hz), 9,14 (1H, d, J = 1.5 Hz), of 11.26 (1H, s).

2-(Benzamido)-4-(4-(methanesulfonyl)phenyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.33 (3H, s), EUR 7.57-of 7.70 (4H, m), 7,99 shed 8.01 (4H, m), of 8.09 (2H, d, J = 8.6 Hz), 8,19 (1H, d, J = 8,3 Hz), 9,13 (1H, d, J = 1.7 Hz), to 12.28 (1H, s).

Example 14

61 mg of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan, 55 mg of sodium carbonate and 30 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 90°C for 12 hours. After cooling the reaction mixture to room temperature, add 41 mg of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan and 22 mg of sodium carbonate and the mixture was stirred at 90°C for 12 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and the tub over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 1.0 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l and 2.0 ml of ethanol, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture of hydrochloric acid with a concentration of 0.6 mol/l, and the solid is separated by filtration and purified column chromatography on silica gel with reversed phase [eluent: aqueous solution of 50-100% acetonitrile/0.1% of triperoxonane acid], while receiving 6,2 mg of 2-(benzamido)-4-(furan-3-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,97 (1H, d, J = 1.7 Hz), 7,47 (1H, DD, J = 8,3) and 1.7 Hz), to 7.59-of 7.69 (3H, m), 7,83 (1H, t, J = 1.6 Hz), 7,98-of 8.00 (2H, m), of 8.06 (1H, d, J = 8,3 Hz), 8,32 (1H, s), to 8.94 (1H, d, J = 1.7 Hz), 12,29 (1H, s).

Example 15

The following connection receive the same manner as in example 14.

2-(Benzamido)-4-(2,3-dihydrobenzo[1,4]dioxin-6-yl)benzoic acid

1H-NMR (DMSO-d6) δ: or 4.31 (4H, s), 7,02 (1H, d, J = 8,8 Hz), 7,21-7,24 (2H, m), 7,46 (1H, DD, J = 8,3, 2.0 Hz), 7,60-of 7.69 (3H, m), 7,97-to 7.99 (2H, m), of 8.09 (1H, d, J = 8.5 Hz), of 9.02 (1H, d, J = 1.7 Hz).

Example 16

56 mg (4-(tert-butyl)phenyl)Bronevoy acid, 55 mg of sodium carbonate and 30 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of methyl 2-(benzamido)-4-b is amentata in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 90°C for 21 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 1.0 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l and 5.0 ml of ethanol, and the mixture is stirred at room temperature for 1 hour and 30 minutes. To the reaction mixture of hydrochloric acid with a concentration of 0.5 mol/l and ethyl acetate. The organic layer is separated and the solvent is evaporated under reduced pressure, thus obtaining a 9.3 mg of 2-(benzamido)-4-(4-tert-butyl)phenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 1.28 (9H, s), 7,41-EUR 7.57 (8H, m), 7,78-7,80 (2H, m), of 7.90 (1H, DD, J = 8,1) and 1.7 Hz), of 8.06 (1H, d, J = 1.7 Hz), to 9.93 (1H, s), to 13.09 (1H, s).

Example 17

56 mg benzothiophen-2-Bronevoy acid, 55 mg of sodium carbonate and 30 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of methyl 2-(benzamido)-4-bromans the ATA 2.5 ml of N,N-dimethylacetamide, and the mixture was stirred at 90°C for 12 hours. After cooling the reaction mixture to room temperature, add 37 mg benzothiophen-2-Bronevoy acid and 22 mg of sodium carbonate and the mixture was stirred at 90°C for 12 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 1.0 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l and 2.0 ml of ethanol, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture of hydrochloric acid with a concentration of 0.6 mol/l, and the solid is separated by filtration, while receiving 2.5 mg 2-(benzamido)-4-(benzothiophen-2-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,41-7,46 (2H, m), to 7.61-of 7.70 (4H, m), 7,94-of 8.06 (5H, m), 8,15 (1H, d, J = 8,3 Hz), 9,24 (1H, s), 12,30-12,50 (1H, usher.).

Example 18

51 mg of 4-acetylphenylalanine acid, 61 mg of sodium bicarbonate and 12 mg of tetrakis(trip nilpotent)palladium(0) are added to a solution, containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate in a mixture of 2.0 ml of toluene, 0.6 ml of ethanol and 0.4 ml of water, and the mixture is stirred under pressure at 160°C for 5 minutes. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration, add ethyl acetate and hydrochloric acid with a concentration of 0.5 mol/l and the solid is separated by filtration. The obtained solid is added to a mixed solution of 1.0 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l and 5.0 ml of ethanol and the mixture is stirred at room temperature for 1 hour and 30 minutes. To the reaction mixture of hydrochloric acid with a concentration of 0.6 mol/l and ethyl acetate. The organic layer is separated and the solvent is evaporated under reduced pressure, while receiving 50 mg of 4-(4-acetylphenyl)-2-(benzamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,64 (3H, s), to 7.59-of 7.70 (4H, m), 7,89 (2H, d, J = 8,3 Hz), 7,99 shed 8.01 (2H, m)to 8.12 (2H, d, J = 8,3 Hz), 8,17 (1H, d, J = 8,3 Hz), 9,14 (1H, d, J = 1.7 Hz), to 12.28 (1H, s), 13,80-14,10 (1H, usher.).

Example 19

56 mg of 2,4-diftorhinolonom acid, 63 mg of sodium carbonate and 34 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 80 mg of methyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture p is remediat at 90°C for 20 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and hydrochloric acid with a concentration of 1.2 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 1.0 ml of aqueous sodium hydroxide with a concentration of 1.0 mol/l and 4.0 ml of ethanol and the mixture is stirred at room temperature for 1 hour. To the reaction mixture of hydrochloric acid with a concentration of 0.6 mol/l and the solid is separated by filtration, while receiving 24 mg of 2-(benzamido)-4-(2,4-differenl)benzoic acid.

1H-NMR (DMSO-d6) δ: 7,28 (1H, TD, J = 8,2 Hz, J = 2.2 Hz), 7,39 (1H, dt, J = 8,4, and 1.6 Hz), 7,42-of 7.48 (1H, m), to 7.59-of 7.70 (4H, m), of 7.96-to 7.99 (2H, m), 8,15 (1H, d, J = 8.1 Hz), of 8.95 (1H, d, J = 1.4 Hz), 12,24 (1H, s).

Examples 20-22

Compounds shown in table 9 was obtained in the same manner as in example 19.

Table 9
Example No.R3
20
21
22

2-(Benzamido)-4-(4-forfinal)benzoic acid

1H-NMR (DMSO-d6) δ: of 7.36-7,40 (2H, m), 7,51 (1H, DD, J = 8,1, 2.0 Hz), 7,60-of 7.69 (3H, m), to 7.77-7,81 (2H, m), 7,98-of 8.00 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 9,06 (1H, s).

2-(Benzamido)-4-(2-methoxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.80 (3H, s), to 7.09 (1H, TD, J = 7,4, 1.0 Hz), 7,17 (1H, d, J = 7.8 Hz), 7,32-7,37 (2H, m), 7,41 was 7.45 (1H, m), to 7.59-to 7.68 (3H, m), of 7.96-7,98 (2H, m), 8,08 (1H, d, J = 8,3 Hz), 8,88 (1H, t, J = 1,6 Hz).

2-(Benzamido)-4-(4-methoxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: a 3.83 (3H, s), 7,09 for 7.12 (2H, m), 7,49 (1H, DD, J = 8,3) and 1.7 Hz), to 7.59-7,72 (5H, m), 7,98-of 8.00 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 9,06 (1H, s), 12,20-12,40 (1H, usher.).

Example 23

of 0.83 ml of triethylamine, 34 mg of palladium acetate, and 0.69 ml of styrene are added to a solution containing 1.0 g of methyl 2-(benzamido)-4-bromobenzoate and 91 mg of tri-(o-tolyl)phosphine in 10 ml of N,N-dimethylacetamide, and the mixture is stirred under nitrogen atmosphere at 120°C for 1 hour and 30 minutes. After cooling the reaction mixture to room temperature, add 0.35 ml of styrene and 5 mg of palladium acetate and the mixture is stirred at 120°C for 2 hours. After cooling, re klonoa mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate

= 8:1], while receiving 0.18 g of methyl 2-(benzamido)-4-((E)-2-phenylphenyl)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 3.97 (3H, s), 7,16 (1H, d, J = 16.4 Hz), 7,26-7,41 (5H, m), 7,52-to 7.59 (5H, m), 8,06-8,10 (3H, m), 9,17 (1H, d, J = 1.4 Hz), 12,12 (1H, s).

Example 24

and 0.37 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to a solution containing 0.18 g of methyl 2-(benzamido)-4-((E)-2-phenylphenyl)benzoate in a mixture of 2 ml of methanol and 2 ml of tetrahydrofuran, at room temperature, and the mixture was stirred at the same temperature for 7 hours. The solvent is evaporated under reduced pressure, and water is added, and regulate pH to 4.0 with hydrochloric acid with a concentration of 1.0 mol/liter Solids are separated by filtration and purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 2:1], while receiving 65 mg of 2-(benzamido)-4-((E)-2-phenylphenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,31-7,44 (5H, m), 7,49 (1H, DD, J = 8,4, 1.3 Hz), 7,60-to 7.67 (3H, m), 7,71 (2H, d, J = 7,6 Hz), to 7.99 (2H, d, J = 7,1 Hz),of 8.06 (1H, d, J = 8,4 Hz), to 8.94 (1H, d, J = 1.3 Hz), 12,27 (1H, s), 13,65-13,85 (1H, usher.).

Example 25

20 mg of 5% palladium on coal are added to a solution containing 0.10 g of 2-(benzamido)-4-((E)-2-phenylphenyl)benzoic acid in a mixture of 1 ml of methanol and 2 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 5 hours. Insoluble matter is removed by filtration and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, to thereby obtain 69 mg of 2-(benzamido)-4-venetiancasino acid as a white solid.

1H-NMR (DMSO-d6) δ: 2.91 in-2,99 (4H, m), 7,07 (1H, DD, J = 8,1, 1,4 Hz), 7,17-7,20 (1H, m), 7,26-7,31 (4H, m), 7,58-to 7.67 (3H, m), 7,95-7,98 (3H, m), 8,67 (1H, d, J = 1.4 Hz), 12,40-12,50 (1H, usher.).

Example 26

0.037 ml vinylcyclohexane, 87 mg of cesium carbonate, 13 mg of tetrabutylammonium bromide and 21 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 50 mg of tert-butyl 2-(benzamido)-4-bromobenzoate in 1.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 48 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated, and the solvent is pariwat under reduced pressure after washing with 10% aqueous citric acid solution. To the obtained residue, add 5 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 55-100% acetonitrile/0.1% of triperoxonane acid], while receiving 2,9 mg of 2-(benzamido)-4-((E)-2-cyclohexylphenol)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,16-of 1.36 (5H, m), 1,64-of 1.81 (5H, m), 2,16-of 2.24 (1H, m), 6.42 per-6,44 (2H, m), 7,24 (1H, DD, J = 8,3) and 1.7 Hz), 7,58-to 7.67 (3H, m), 7.95 is-to 7.99 (3H, m), 8,76 (1H, s), 12,20-12,40 (1H, usher.).

Example 27

The following connection receive the same manner as in example 26.

2-(Benzamido)-4-((E)-3-cyclohexyl-1-propenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 0,92 of 1.28 (5H, m), 1,39-1,49 (1H, m), 1,61-of 1.74 (5H, m), 2,12-to 2.18 (2H, m), 6,45-6,47 (2H, m), 7,25 (1H, DD, J = 8,3, 1.5 Hz), 7,58-to 7.67 (3H, m), 7.95 is-to 7.99 (3H, m), is 8.75 (1H, d, J = 1.5 Hz), 12,20-to 12.35 (1H, user.).

Example 28

0,074 ml vinylcyclohexane, 0.17 g of cesium carbonate, 26 mg of tetrabutylammonium bromide and 42 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 0.10 g of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 48 hours. After the OHL the input voltage to the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated, and the solvent is evaporated under reduced pressure after washing with 10% aqueous citric acid solution. To the obtained residue, add 2.4 ml of tetrahydrofuran, 0.6 ml of water at 0.42 g of sodium formiate, of 0.44 ml of acetic acid and 50 mg of 3.9% palladium on coal (Ethylenediamine complex), and the mixture was stirred at 50°C for 12 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], while receiving 4,8 mg of 2-(benzamido)-4-(2-cyclohexylethyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 0,89-0,98 (2H, m), 1,12-of 1.27 (4H, m), 1,48-1,78 (7H, m), 2,65-2,69 (2H, m), 7,05 (1H, DD, J = 8,2, 1,6 Hz), 7,58-to 7.67 (3H, m), 7,94-of 7.97 (3H, m), to 8.62 (1H, d, J = 1.6 Hz), 12,20-to 12.35 (1H, usher.).

Example 29

The following connection receive the same manner as in example 28.

2-(Benzamido)-4-(3-cyclohexylprop)benzoic acids of the Sabbath.

1H-NMR (DMSO-d6) δ: 0,80-of 0.91 (2H, m), 1,09-of 1.24 (6H, m), 1,59 is 1.70 (7H, m), 2,62-to 2.65 (2H, m), 7,05 (1H, DD, J = 8,2, 1,6 Hz), 7,55-the 7.65 (3H, m), 7,94-7,98 (3H, m), to 8.62 (1H, d, J = 1.6 Hz), 12,25 (1H, s), 13,64 (1H, s).

Example 30

of 0.28 ml of triethylamine and 0.12 ml of benzoyl chloride successively added to a solution containing 0.31 g of tert-butyl 2-amino-4-(3-phenylpropyl)benzoate in 3 ml of methylene chloride under ice cooling, and the mixture is stirred at room temperature for 17 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 20:1], while receiving of 0.48 g of tert-butyl 2-(benzamido)-4-(3-phenylpropyl)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 1.62 (9H, s), 1,96-of 2.05 (2H, m), 2,68 (2H, t, J = 7,7 Hz), of 2.72 (2H, t, J = 7.8 Hz), 6,92 (1H, DD, J = 8,3, 1,6 Hz), 7.18 in-7,22 (3H, m), 7,26-7,30 (2H, m), 7,52-7,56 (3H, m), to 7.93 (1H, d, J = 8,3 Hz), 8,05-8,07 (2H, m), 8,81 (1H, d, J = 1.6 Hz), 12,22 (1H, s).

Example 31

A solution containing of 0.48 g of tert-butyl 2-(benzamido)-4-(3-phenylpropyl)benzoate in 4.8 ml triperoxonane acid, stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 1:1], while receiving 0.20 g 2-(benzamido)-4-(3-phenylpropyl)benzo is Noah acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,89-of 1.97 (2H, m)to 2.65 (2H, t, J = 7.9 Hz), 2,69 (2H, t, J = 8,3 Hz), 7,07 (1H, DD, J = 8,2, 1,6 Hz), 7,17-of 7.25 (3H, m), 7,28-to 7.32 (2H, m), 7,58-the 7.65 (3H, m), 7.95 is-to 7.99 (3H, m)8,64 (1H, d, J = 1.6 Hz), 12,23 (1H, s), 13,55-of 13.75 (1H, usher.).

Example 32

of 0.34 ml of triethylamine and 0.15 ml of benzoyl chloride successively added to a solution containing 0.40 g of tert-butyl 2-amino-4-(4-phenylbutyl)benzoate in 4 ml of methylene chloride under ice cooling, and the mixture is stirred at room temperature for 19 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 20:1], while receiving 0.50 g of tert-butyl 2-(benzamido)-4-(4-phenylbutyl)benzoate as a white solid.

1H-NMR (CDCl3) δ: 1,55-of 1.73 (4H, m)of 1.62 (9H, s)of 2.64 (2H, t, J = 7.2 Hz), a 2.71 (2H, t, J = 7.2 Hz), make 6.90 (1H, DD, J = 8,3, 1,4 Hz), 7,15-7,20 (3H, m), 7,25-7,28 (2H, m), 7,51-7,56 (3H, m), 7,92 (1H, d, J = 8,3 Hz), 8,05-8,07 (2H, m), 8,80 (1H, d, J = 1.4 Hz), 12,22 (1H, s).

Example 33

A solution containing 0.50 g of tert-butyl 2-(benzamido)-4-(4-phenylbutyl)benzoate 4.9 ml triperoxonane acid, stirred at room temperature for 2 hours and 30 minutes. The solid is separated by filtration, thus obtaining 0.16 g of 2-(benzamido)-4-(4-phenylbutyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6)δ: 1,55-1,70 (4H, m)2,60-to 2.74 (4H, m),? 7.04 baby mortality (1H, DD, J = 8,2, 1.3 Hz), 7,14-7,21 (3H, m), 7,25-7,28 (2H, m), 7,58-the 7.65 (3H, m), 7,94-7,98 (3H, m), to 8.62 (1H, d, J = 1.3 Hz), 12,22 (1H, s).

Example 34

0,082 ml of triethylamine, 44 mg of 2-frailcare and 2.0 ml of methylene chloride are added to a solution containing 50 mg of tert-butyl 2-amino-4-penicillinate in 1.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture are added 380 mg aminomethylpropanol polystyrene, and the mixture is stirred at room temperature over night. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(furan-2-carboxamido)-4-venetianskt.

2.0 ml triperoxonane acids are added to the obtained tert-butyl 2-(furan-2-carboxamido)-4-penicillinate and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, while receiving 32 mg of 2-(furan-2-carboxamido)-4-venetiancasino acid in the form of the aircraft the CSO solids.

1H-NMR (DMSO-d6) δ: 2.91 in are 2.98 (4H, m), of 6.75 (1H, DD, J = 3,4, 1.7 Hz), 7,07 (1H, DD, J = 8,2, 1.3 Hz), 7,16-7,30 (6H, m), 7,95 (1H, d, J = 8,3 Hz), 8,00 (1H, s), 8,61 (1H, s), 12,19 (1H, s), 13,50-13,70 (1H, usher.).

Examples of 35-54

Compounds shown in table 10, receive the same manner as in example 34.

Table 10
No.
example
R2# exampleR2# exampleR2
354249
364350
3744 51
384552
394653
404754
4148

2-(2,4-Differentaite)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-of 3.00 (4H, m), 7,10 (1H, DD, J = 8,0, 1.5 Hz), 7,16-7,20 (1H, m), 7,26-7,33 (5H, m)to 7.50 (1H, DDD, J = 11,4, and 9.2, 2.4 Hz), 7,94 (1H, d, J = 8.0 Hz), 8,01 (1H, TD, J = 8,8, 6,7 Hz), 8,63 (1H, s), 11,96 (1H, s), 13,54-13,64 (1H, usher.).

2-(Cinnamamide)-4-fenetylline the Naya acid

1H-NMR (DMSO-d6) δ: 2,89 are 2.98 (4H, m), to 6.88 (1H, d, J = 15.6 Hz), 7,05 (1H, DD, J = 8,3, 1.5 Hz), 7,16-7,30 (5H, m), 7,42-47 (3H, m), a 7.62 (1H, d, J = 15.6 Hz), 7,73 to 7.75 (2H, m), to $ 7.91 (1H, d, J = 8.0 Hz), 8,55 (1H, s), 11,37 (1H, C), 13,40-13,60 (1H, usher.).

2-(Cyclohexanecarboxylate)-4-phenetylamine acid

1H-NMR (DMCO-d6) δ: at 1.17 to 1.47 (5H, m), and 1.63 to 1.76 (3H, m), 1,87-of 1.95 (2H, m), of 2.25 to 2.35 (1H, m), 2,86 of 2.92 (4H, m), 7,00 (1H, DD, J = 8,0, 1.7 Hz), 7,16-7,29 (5H, m), 7,88 (1H, d, J = 8,3 Hz), 8,49 (1H, s), 11,22 (1H, s), 13,35-13,55 (1H, usher.).

2-(4-Perbenzoic)-4-phenetylamine acid

1H-NMR (DMCO-d6) δ: 2,90-of 3.00 (4H, m), to 7.09 (1H, DD, J = 8,1) and 1.7 Hz), 7,16-7,20 (1H, m), 7,26-7,30 (4H, m), 7,45 (2H, t, J = 8,9 Hz), of 7.96 (1H, d, J = 8.1 Hz), 8,00-of 8.04 (2H, m), to 8.62 (1H, d, J = 1.7 Hz), 12,16 (1H, s).

4-Phenethyl-2-(thiophene-2-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,90 are 2.98 (4H, m), 7,07 (1H, DD, J = 8,2, 1,6 Hz), 7,16-7,30 (6H, m), 7,74 (1H, DD, J = 3,7, 1.0 Hz), 7,93-of 7.96 (2H, m), charged 8.52 (1H, s), 12,20 (1H, s).

2-(Cyclopropanecarboxamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 0,85-0,87 (4H, m), 1,67-of 1.73 (1H, m), 2,86-only 2.91 (4H, m), 7,00 (1H, DD, J = 8,2, 1,6 Hz), 7,15-7,29 (5H, m), 7,88 (1H, d, J = 8,2 Hz), to 8.41 (1H, d, J = 1.6 Hz), 11,38 (1H, s), 13,35-13,60 (1H, usher.).

4-Phenethyl-2-(2-phenoxyacetamide)benzoic acid

1H-NMR (DMSO-d6) δ: 2,88 are 2.98 (4H, m), to 4.73 (2H, s), 7,00-7,10 (4H, m), 7,16-7,37 (7H, m), 7,92 (1H, d, J = 8.0 Hz), 8,63 (1H, d, J = 1.7 Hz), 12,19 (1H, s), 13,50-of 13.75 (1H, usher.).

4-Phenethyl-2-(pyridine-2-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,92-to 2.99 (4H, m), 7,08-7,10 (1H, m), 7,16-7,20 (1H, m), 7,26-7,31 (4H,m), to 7.67-of 7.70 (1H, m), of 7.96 (1H, d, J = 8,3 Hz), of 8.09 (1H, TD, J = 7,7, 1.5 Hz), to 8.20 (1H, d, J = 7.8 Hz), 8,70 is 8.75 (1H, m), 8,80 (1H, d, J = 1.5 Hz), 13,07 (1H, s), 13,44 (1H, s).

Triptorelin 4-phenethyl-2-(pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2.91 in-a 3.01 (4H, m), 7,11 (1H, DD, J = 8,3, 1.5 Hz), 7,16-7,20 (1H, m), 7,27-7,29 (4H, m), the 7.65 (1H, DD, J = 7,8, and 4.9 Hz), of 7.97 (1H, d, J = 8,3 Hz), 8,30 (1H, dt, J = 8,1, 1.9 Hz), at 8.60 (1H, s), 8,82 (1H, DD, J = 4,9, 1.2 Hz), 9,13 (1H, d, J = 2.2 Hz), 12,20 (1H, s), 13,60-13,80 (1H, usher.).

4-Phenethyl-2-(2,2-diphenylacetamide)benzoic acid

1H-NMR (DMSO-d6) δ: 2,86-of 2.93 (4H, m), 5,28 (1H, s), 7,02 (1H, DD, J = 8,0, 1.7 Hz), 7,15-7,40 (15H, m), to 7.84 (1H, d, J = 8.1 Hz), 8,48 (1H, s), 11,34 (1H, s), 13,30-13,40 (1H, usher.).

2-(Benzo[1,3]dioxol-5-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2.91 in are 2.98 (4H, m), 6,16 (2H, s), 7,06 (1H, DD, J = 8,1) and 1.7 Hz), 7,12 (1H, d, J = 8,3 Hz), 7,15-7,20 (1H, m), 7,25-7,30 (4H, m), 7,42 (1H, d, J = 2.0 Hz), 7,53 (1H, DD, J = 8,2, 1.8 Hz), 7,95 (1H, d, J = 8,1 Hz), 8,63 (1H, s), 12,06 (1H, s).

2-(Isoxazol-5-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-a 3.01 (4H, m), 7,14-7,30 (7H, m), of 7.97 (1H, d, 8.1 Hz), 8,53 (1H, s), 8,86 (1H, d, J = 1.5 Hz), 12,41 (1H, s).

2-(Benzothiophen-3-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,94-a 3.01 (4H, m), to 7.09 (1H, DD, J = 8,2, 1,6 Hz), 7,17-7,21 (1H, m), 7,28-7,30 (4H, m), 7,47-rate of 7.54 (2H, m), of 7.96 (1H, d, J = 8.1 Hz), 8,11-8,13 (1H, m), 8,49-charged 8.52 (2H, m), to 8.62 (1H, d, J = 1.2 Hz), a 12.03 (1H, ), 13,50-13,70 (1H, usher.).

2-(Benzofuran-2-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,1-a 3.01 (4H, m), 7,12 (1H, DD, J = 8,4, and 1.6 Hz), 7,17-7,21 (1H, m), 7,26-7,29 (4H, m), 7,40 (1H, t, J = 7,6 Hz), 7,54 (1H, t, J = 7.2 Hz), of 7.70 (1H, d, J = 8.5 Hz), 7,73 (1H, s), a 7.85 (1H, d, J = 7.8 Hz), 7,98 (1H, d, J = 8.0 Hz,), 8,66 (1H, s), 12,54 (1H, s).

2-(2,3-Dihydrobenzo[1,4]dioxin-6-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90 are 2.98 (4H, m), or 4.31-4,34 (4H, m), 7,05 (2H, d, J = 8,3 Hz), 7,16-7,20 (1H, m), 7,25-7,30 (4H, m), 7,44-7,47 (2H, m), 7,94 (1H, d, J = 8,3 Hz), 8,65 (1H, d, J = 1.5 Hz), 12,12 (1H, s).

2-(Benzofuran-5-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,93-of 3.00 (4H, m), was 7.08 (1H, DD, J = 8,1) and 1.7 Hz), 7,15-7,21 (2H, m), 7,28-7,31 (4H, m), 7,81 (1H, d, J = 8,8 Hz), to 7.93 (1H, DD, of 8.8, 1.9 Hz), of 7.97 (1H, d, 8,3 Hz), 8,16 (1H, d, J = 2.2 Hz), 8,30 (1H, d, J = 1.7 Hz), 8,69 (1H, s), 12,27 (1H, s).

2-(2-Morpholinopropan-5-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,91-of 2.97 (4H, m), 3,61-of 3.64 (4H, m), 3,70-and 3.72 (4H, m), 6,98 (1H, d, J = 9.0 Hz),? 7.04 baby mortality (1H, DD, J = 8,3, 1.5 Hz), 7,16-7,20 (1H, m), 7,25-7,30 (4H, m), 7,94 (1H, d, J = 8,3 Hz), 8,02 (1H, DD, J = 9,0, 2.5 Hz), 8,64 (1H, d, J = 1.5 Hz), 8,72 (1H, d, J = 2.5 Hz), 12,00-12,10 (1H, usher.).

2-(Benzothiophen-5-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,93-a 3.01 (4H, m), 7,07-7,10 (1H, m), 7,17-7,22 (1H, m), 7,28-7,31 (4H, m), of 7.64 (1H, d, J = 5.6 Hz), to $ 7.91-7,98 (3H, m), 8,24 (1H, d, J = 8,3 Hz)and 8.50 (1H, s), to 8.70 (1H, s), 12,35 (1H, s).

2-(Benzothiazol-2-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2.91 in was 3.05 (4H, m), 7,15-7,31 (6H, m), 7,62-7,71 (2H, m), of 8.00 (1H, d, J = 7.8 Hz), 8,19 (1H, d, J = 7.8 Hz), 8,29 (1H, d, J = 7.8 Hz), 8,69 (1H, s), 12,98 (1H, s).

4-Phenethyl-2-(1-phenyl-1H-pee the azole-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,84-to 2.94 (4H, m), 7,05 (1H, d, J = 2.0 Hz), was 7.08 (1H, DD, J = 8,1) and 1.7 Hz), 7,14-7,27 (5H, m), 7,43-to 7.50 (5H, m), 7,86 (1H, d, J = 2.2 Hz), 7,94 (1H, d, J = 8.1 Hz), of 8.37 (1H, s), 12,04 (1H, s).

Example 55

0,082 ml of triethylamine, 39 mg benzylchloride and 2.0 ml of methylene chloride are added to a solution containing 50 mg of tert-butyl 2-amino-4-penicillinate in 1.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture are added 380 mg aminomethylpropanol polystyrene, and the mixture is stirred at room temperature over night. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel (Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1), while receiving tert-butyl-2-(benzylmaleimide)-4-venetianskt.

2.0 ml triperoxonane acids are added to the obtained tert-butyl 2-(benzylmaleimide)-4-penicillinate, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 65-100% Aceto is itila/0,1% triperoxonane acid], while receiving 5.1 mg 2-(benzylmaleimide)-4-venetiancasino acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,86-2,95 (4H, m), a 4.53 (2H, s), 7,03 (1H, DD, J = 7,9, and 1.6 Hz), 7,11-to 7.15 (3H, m), 7,21-7,33 (8H, m), 7,88 (1H, d, J = 8.0 Hz).

Examples 56, 57

Compounds shown in table 11, receive the same manner as in example 55.

Table 11
# exampleR2
56
57

4-Phenethyl-2-(((E)-2-phenylphenyl)sulphonamido)benzoic acid

1H-NMR (DMSO-d6) δ: was 2.76 is 2.80 (2H, m), 2,90-to 2.94 (2H, m)6,94 (1H, DD, J = 8,1, 1.5 Hz), 7,09-7,19 (5H, m), 7,38-7,44 (5H, m), 7,72-to 7.77 (3H, m), to 7.84 (1H, d, J = 8.1 Hz), 11,02 (1H, s).

2-(Benzosulfimide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,78-2,82 (2H, m), 2,87-only 2.91 (2H, m), 6,92 (1H, d, J = 8.0 Hz), 7,12-to 7.18 (3H, m), 7,22-7,26 (2H, m), 7,39 (1H, s), 7,52-7,56 (2H, m), of 7.64 (1H, t, 7.4 Hz), 7,74 for 7.78 (3H, m).

Example 58

0,031 ml of 2-iodotoluene, 81 g of cesium carbonate, 12 mg of tetrabutylammonium bromide and 19 mg deposited on the polymer di(acetato)dicyclo silvesterparty(II) added to the solution, containing 40 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 1.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated, and the solvent is evaporated under reduced pressure after washing with 10% aqueous citric acid solution. To the obtained residue, add 5 ml triperoxonane acid and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 65-100% acetonitrile/0.1% of triperoxonane acid], while receiving 2.8 mg 2-(benzamido)-4-((E)-2-(2-were)vinyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 2.45 (3H, s), 7,21-of 7.25 (4H, m), 7,52-of 7.69 (5H, m), 7,76 for 7.78 (1H, m), 7,98-of 8.00 (2H, m), of 8.06 (1H, d, J = 8,3 Hz), to 8.94 (1H, s), 12,27 (1H, s).

Examples 59-66

Compounds shown in table 12, receive the same manner as in example 58.

Table 12
No.
example
Rsup> 3No.
example
R3
5963
6064
6165
6266

2-(Benzamido)-4-((E)-2-(4-forfinal)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7.23 percent-7,42 (4H, m), of 7.48 (1H, DD, J = 8,2, 1,6 Hz), 7,60-of 7.69 (3H, m), 7,75-7,79 (2H, m), to 7.99 (2H, d, J = 6.8 Hz), of 8.06 (1H, d, J = 8,3 Hz), 8,93 (1H, s)to 12.28 (1H, s).

2-(Benzamido)-4-((E)-2-(3-fluoro-4-were)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 2.26 (3H, s), 7,29-of 7.69 (9H, m), to 7.99 (2H, d, J = 7,1 Hz), of 8.06 (1H, d, J = 8,3 Hz), 8,93 (1H, s), 12,27 (1H, s).

2-(Benzamido)-4-((E)-2-(3-nitrophenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,54-7,73 (7H, m), 7,98-of 8.00 (2H, m), of 8.09 (1H, d, J = 8,3 Hz), 8,15-to 8.20 (2H, m), 8,56 (1H, s), 8,98 (1H, d, J = 1.5 Hz), 12,24(1H, C).

4-((E)-2-(4-Acetylphenyl)vinyl)-2-(benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,60 (3H, s), 7,45-of 7.69 (6H, m), a 7.85 (2H, d, J = 8,3 Hz), 7,98-of 8.00 (4H, m), 8,08 (1H, d, J = 8,3 Hz), 8,97 (1H, d, J = 1.4 Hz), 12,27 (1H, s).

2-(Benzamido)-4-((E)-2-(4-methoxyphenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.80 (3H, s), 6,98 (1H, d, J = 8,8 Hz), 7.18 in-7,22 (2H, m), 7,34 (1H, d, J = 16,3 Hz), 7,44 (1H, DD, J = 8,3) and 1.7 Hz), EUR 7.57-of 7.69 (5H, m), 7,98-with 8.05 (3H, m), 8,91 (1H, s), 12,29 (1H, s).

2-(Benzamido)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 3,82 (3H, s), 6.89 in-6,91 (1H, m), 7,26-7,38 (5H, m), of 7.48 (1H, DD, J = 8,4, and 1.6 Hz), to 7.59-of 7.69 (3H, m), 7,98-of 8.00 (2H, m), of 8.06 (1H, d, J = 8,3 Hz), to 8.94 (1H, d, J = 1.7 Hz), 12,20-12,50 (1H, usher.).

2-(Benzamido)-4-((E)-2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 4,27 (4H, s), to 6.88 (1H, d, J = 8,3 Hz), 7,16-7,28 (4H, m), 7,42 (1H, DD, J = 8,2, 1.3 Hz), to 7.59-to 7.68 (3H, m), 7,98-of 8.04 (3H, m), 8,89 (1H, s).

2-(Benzamido)-4-((E)-2-(4-(trifluoromethyl)phenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 7.48 (1H, d, J = 16.6 Hz), 7,53-of 7.69 (5H, m), 7,76 (2H, d, J = 8.0 Hz), to 7.93 (2H, d, J = 8.0 Hz), 7,98-of 8.00 (2H, m), 8,08 (1H, d, J = 8,3 Hz), 8,97 (1H, d, J = 1.5 Hz).

Example 67

to 0.060 ml 3-iodoanisole, 0.16 g of cesium carbonate, 24 mg of tetrabutylammonium bromide and 39 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 80 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 2.0 ml of toluene, at room t is mperature, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated, and the solvent is evaporated under reduced pressure after washing with 10% aqueous citric acid solution. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], thus obtaining 2-(benzamido)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid.

1.0 ml of methanol, 2.0 ml of ethyl acetate and 2.0 mg of 5% palladium on coal added to the obtained 2-(benzamido)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid, and the mixture is stirred in hydrogen atmosphere at room temperature for 2 hours. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure, thus obtaining 6,3 mg of 2-(benzamido)-4-(2-(3-methoxyphenyl)ethyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,87 (4H, s), of 3.73 (3H, s), 6,74 (1H, DDD, J = 8,2, of 2.5, 1.0 Hz), 6,83-to 6.88 (3H, m), 7,17-7,21 (1H, m), 7,52-of 7.60 (3H, m), 7,92 (1H, d, J = 7.8 Hz), 8,02-with 8.05 (2H, m), 8,61 (1H, d, J = 1.7 Hz).

Por the measures 68-70

Compounds shown in table 13, receive the same manner as in example 67.

Table 13
# exampleR3
68
69
70

2-(Benzamido)-4-(2-(3-fluoro-4-were)ethyl)benzoic acid

1H-NMR (DMSO-d6) δ: 2,18 (3H, s), 2.91 in (4H, s), of 6.96-7,00 (2H, m), 7,05 (1H, d, J = 11,0 Hz), 7,17 (1H, t, J = 7.9 Hz), 7,55-7,63 (3H, m), 7,94 (1H, d, J = 8.0 Hz), 8,00 (2H, d, J = 6.8 Hz), to 8.62 (1H, s).

2-(Benzamido)-4-(2-(4-ethylphenyl)ethyl)benzoic acid

1H-NMR (DMSO-d6) δ: 1,15 (3H, t, J = 7,6 Hz), of 2.56 (2H, square, J = 7,6 Hz), 2,86-2,96 (4H, m), 7,05 (1H, d, J = 8,3 Hz), 7,12 (2H, d, J = 7.9 Hz), 7,18 (2H, d, J = 8.0 Hz), EUR 7.57-7,66 (3H, m), 7.95 is-to 7.99 (3H, m), 8,67 (1H, s), 12,65-12,95 (1H, usher.).

2-(Benzamido)-4-(2-(2-were)ethyl)benzoic acid

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), 2,89 (4H, s), 7,05-7,21 (5H, m), EUR 7.57-7,66 (3H, m), 7,97-to 7.99 (3H, m), 8,69 (1H, d, J = 1.5 Hz), 12,55-is 12.85 (1H, usher.).

Example 71

0,087 ml 4-bromobenzonitrile, 0.20 g of the carbonate as what I 30 mg of tetrabutylammonium bromide and 49 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 100 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 2.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 48 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated, and the solvent is evaporated under reduced pressure after washing with 10% aqueous citric acid solution. To the obtained residue, add 2.4 ml of tetrahydrofuran, 0.6 ml of water at 0.42 g of sodium formiate, of 0.44 ml of acetic acid and 50 mg of 3.9% palladium on coal (Ethylenediamine complex), and the mixture was stirred at 50°C for 12 hours. The reaction mixture is cooled to room temperature, and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], while receiving 21 mg of 2-(benzamido)-4-(2-(4(trifluoromethyl)phenyl)ethyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 3,00-of 3.06 (4H, m), to 7.09 (1H, DD, J = 8,1, 1.5 Hz), to 7.50 (2H, d, J = 8.1 Hz), 7,58-to 7.67 (5H, m), 7,95-7,98 (3H, m), 8,66 (1H, s), 12,24 (1H, s).

Example 72

The following connection receive the same manner as in example 71.

2-(Benzamido)-4-(2-(4-forfinal)ethyl)benzoic acid

1H-NMR (DMSO-d6) δ: 2.91 in are 2.98 (4H, m), 7,06 for 7.12 (3H, m), 7,28-7,31 (2H, m), 7,58-to 7.67 (3H, m), of 7.96 (3H, d, J = 7.8 Hz), 8,66 (1H, d, J = 1.2 Hz), 12,21 (1H, s).

Example 73

0.35 g of potassium permanganate is added to the suspension containing 0,70 g of N-((5-benzoyl-2-methyl)phenyl)benzamide in 7 ml of pyridine and 7 ml of water at room temperature, and the resulting mixture is refluxed for 30 minutes. After cooling the reaction mixture to room temperature, add 0.35 g of potassium permanganate and the resulting mixture is refluxed for 30 minutes. After cooling the reaction mixture to room temperature, add 0.35 g of potassium permanganate and the resulting mixture is refluxed for 30 minutes. After cooling, the reaction mixture are added ethyl acetate and the pH is adjusted to 1.3 by adding hydrochloric acid with a concentration of 6.0 mol/l Insoluble substance is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate consequently after the first flush of hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining at 0.42 g of 2-(benzamido)-4-benzoylbenzene acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,52-7,83 (9H, m), 7,95-of 7.97 (2H, m), 8,21 (1H, d, J = 8,3 Hz), 9,05 (1H, d, J = 1.7 Hz), 12,20 (1H, s).

30 mg of 5% palladium on coal are added to a solution containing 0.15 g of the obtained 2-(benzamido)-4-benzoylbenzene acid in a mixture of 1.5 ml of methanol and 2 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for ten hours. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and the solid is separated by filtration, thus obtaining 0.11 g of 2-(benzamido)-4-benzylbenzoate acid as a white solid.

1H-NMR (DMSO-d6) δ: a 4.03 (2H, s), 7,07 (1H, DD, J = 8,1, 1,4 Hz), 7,20-7,34 (5H, m), EUR 7.57-7,66 (3H, m), 7,93-of 7.95 (2H, m), 7,98 (1H, d, J = 8.1 Hz), 8,66 (1H, d, J = 1.4 Hz), 12,36 (1H, s).

Example 74

0,056 ml of triethylamine and 0,029 ml 3-bromobenzonitrile successively added to a solution containing 57 mg of tert-butyl 2-amino-4-phenoxybenzoate in 3.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 1 the Asa. To the reaction mixture is added saturated aqueous solution of sodium bicarbonate. The organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(3-bromobenzene)-4-phenoxybenzoate.

5 ml triperoxonane acids are added to the obtained tert-butyl 2-(3-bromobenzene)-4-phenoxybenzoate, and the mixture is stirred at room temperature for 5 minutes. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 31 mg of 2-(3-bromobenzene)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,9 and 2.5 Hz), 7,15-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,53 (2H, m), 7,56 (1H, t, J = 7.9 Hz), 7,83-7,88 (1H, m), 7,88-a 7.92 (1H, m), 8,05-8,10 (2H, m), with 8.33 (1H, d, J = 2.5 Hz), to 12.44 (1H, ), 13,70-13,90 (1H, usher.).

Example 75

The suspension containing 0.15 g of methyl 2-(benzamido)-4-ethynylbenzoate, 0,090 ml iodirovannoi benzene, 5 mg of copper iodide(I), 20 mg of bis(triphenylphosphine)palladium(II)chloride and 0.15 ml of triethylamine in 1.5 ml of toluene is stirred under nitrogen atmosphere at room temperature for 2 hours. To the reaction mixture are added ethyl acetate and hloristovodorodnykh acid with a concentration of 1.0 mol/L. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate

= 8:1], while receiving of 0.13 g of methyl 2-(benzamido)-4-(phenylethynyl)benzoate as a white solid.

1H-NMR (CDCl3) δ: 3,98 (3H, s), 7,27 (1H, DD, J = 8,2, 1,6 Hz), 7,37-7,39 (3H, m), 7,52-7,58 (5H, m), 8,05-8,08 (3H, m), 9,16 (1H, d, J = 1.6 Hz), 12,07 (1H, s).

Example 76

of 0.24 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to a solution containing of 0.13 g of methyl 2-(benzamido)-4-(phenylethynyl)benzoate in a mixture of 1 ml of methanol and 2 ml of tetrahydrofuran, at room temperature, and the mixture was stirred at the same temperature for 1 hour and 30 minutes. The solvent is evaporated under reduced pressure, and water is added, and the pH is adjusted to 4.0 with ice cooling hydrochloric acid with a concentration of 1.0 mol/l, the Solid is separated by filtration, thus obtaining 0.11 g of 2-(benzamido)-4-(phenylethynyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,27 (1H, DD, J = 8.0 a, 1,6 Hz), 7,45-7,46 (3H, m), 7,56-7,63 (5H, m), 8,03 (2H, d, J = 6.8 Hz), of 8.09 (1H, d, J = 8.0 Hz), 8,89 (1H, d, J = 1.6 Hz), 14,30-14,50 (1H, usher.).

Example 77

2.6 g of potassium permanganate is added to the suspension containing 1.7 g of N-((2-methyl-5-phenoxy)phenyl)benzamide and 2.0 g of anhydrous magnesium sulfate in 8 ml of tert-butyl alcohol and 8 ml of water at room temperature, and the resulting mixture is refluxed for 5 hours. After cooling the reaction mixture to room temperature, add 0,86 g of potassium permanganate and 0.66 g of anhydrous magnesium sulfate and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/l and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 2:1], while receiving of 0.30 g of 2-(benzamido)-4-phenoxybenzoic acid as a white solid.

1H-NMR (CDCl3) δ: of 6.71 (1H, DD, J = 9,0, 2,5 Hz), 7,13-to 7.15 (2H, m), 7,21-of 7.25 (1H, m), 7,41-7,58 (5H, m), 7,98-of 8.00 (2H, m)to 8.12 (1H, d, J = 9.0 Hz), 8,63 (1H, d, J = 2.5 Hz), 11,94 (1H, s).

Example 78

0,029 ml 2-is amoxicillina added to the solution, containing 40 mg of tert-butyl 2-amino-4-phenoxybenzoate and 0,039 ml of triethylamine in 2.5 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 2 hours. 0.25 g aminomethylpropanol polystyrene is added to the reaction mixture and after stirring at the same temperature over night, add 5 ml of 10% aqueous citric acid solution. The organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate:acetic acid = 20:5:1], while receiving tert-butyl-4-phenoxy-2-(2-phenoxyacetamide)benzoate.

3 ml triperoxonane acids are added to the obtained tert-butyl-4-phenoxy-2-(2-phenoxyacetamide)benzoate, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 38 mg of 4-phenoxy-2-(2-phenoxyacetamide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 4,70 (2H, s), 6,74 (1H, DD, J = 9,0, 2,5 Hz), 7,01 (1H, t, J = 7.4 Hz), was 7.08 (2H, d, J = 8.1 Hz), 7,16 (2H, d, J = 7.8 Hz), 7,27 (1H, t, J = 7.9 Hz), 7,35 (2H, t, J = 7.9 Hz), 7,47 (2H, t, J = 7.9 Hz), 8,03 (1H, d, J = 9.0 Hz), of 8.37 (1H, d, J = 2.5 Hz), 12,32 (1H, s), 13,63 (1H, s).

the reamers 79-97

Compounds shown in table 14, receive the same manner as in example 78.

Table 14
No.
example
-X1-X2-X3-R2# example-X1-X2-X3-R2# example-X1-X2-X3-R2
798693
808794
818895
828996
839097
8491
8592

4 Phenoxy-2-(pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.4 Hz), 7,18 (2H, d, J = 7.8 Hz), 7,29 (1H, t, J = 7.5 Hz), of 7.48-7,51 (2H, m), 7,63 (1H, DD, J = 8.0 a, a 4.9 Hz), 8,08 (1H, d, J = 8,8 Hz), of 8.25 (1H, d, J = 8.0 Hz), a 8.34 (1H, d, J = 2.4 Hz), 8,81 (1H, d, J = 4.9 Hz), the remaining 9.08 (1H, d, J = 1.5 Hz), to 12.52 (1H, s).

2-(Benzo[1,3]dioxol-5-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMCO-d6) δ: x 6.15 (2H, s)6,76 (1H, DD, J = 8,8, 2.4 Hz), 7,10 (1H, d, J = 8.1 Hz), 7,17 (2H, d, J = 7.8 Hz), 7,28 (1H, t, J = 7,4 G is), 7,38 (1H, d, J = 1.7 Hz), 7,47-to 7.50 (3H, m), of 8.06 (1H, d, J = 8,8 Hz), at 8.36 (1H, d, J = 2.4 Hz), of 12.33 (1H, s), 13,55-13,80 (1H, usher.).

2-(Isoxazol-5-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,83 (1H, DD, J = 8,9 and 2.5 Hz), 7,19 (2H, d, J = 7.8 Hz), 7,22 (1H, t, J = 1,0), 7,28-7,31 (1H, m), 7,47-7,51 (2H, m), 8,08 (1H, d, J = 8,9 Hz), of 8.27 (1H, d, J = 2.5 Hz), 8,86 (1H, t, J = 1,0), 12,63 (1H, s).

4 Phenoxy-2-(2-phenylthiazol-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,9, and 2.6 Hz), 7,20 (2H, d, J = 7.8 Hz), 7,29 (1H, t, J = 7.4 Hz), 7,50 (2H, t, J = 7.9 Hz), 7,56-EUR 7.57 (3H, m), of 8.09 (1H, d, J = 8,8 Hz), 8,11-8,13 (2H, m), charged 8.52-8,53 (2H, m), 13,08 (1H, s), 13,69 (1H, s).

2-(2,3-Dihydrobenzo[1,4]dioxin-6-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 4,30-4,34 (4H, m), of 6.75 (1H, DD, J = 8,8, and 2.6 Hz),? 7.04 baby mortality (1H, d, J = 8,3 Hz), 7,17 (2H, d, J = 7.8 Hz), 7,28 (1H, t, J = 7.4 Hz), 7,39-the 7.43 (2H, m), of 7.48 (2H, d, J = 7.9 Hz), of 8.06 (1H, d, J = 8,8 Hz), scored 8.38 (1H, d, J = 2,6 Hz), 12,31 (1H, s), 13,65 (1H, s).

2-(Benzothiophen-3-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,77 (1H, DD, J = 8,8, 2.7 Hz), 7,20 (2H, d, J = 8.0 Hz), 7,29 (1H, t, J = 7.4 Hz), 7,45-7,52 (4H, m), 8,08 (1H, d, J = 8,8 Hz), 8,10-to 8.12 (1H, m), scored 8.38 (1H, d, J = 2.7 Hz), to 8.41-8,43 (1H, m), 8,51 (1H, s), 12,25 (1H, s), 13,64 (1H, s).

2-(Cyclohexanecarboxylate)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 1,14-of 1.42 (5H, m), 1,61-of 1.74 (3H, m), 1,86-of 1.88 (2H, m), 2,23-of 2.30 (1H, m), 6,69 (1H, DD, J = 8,8, and 2.6 Hz), 7,12-7,14 (2H, m), 7,26 (1H, t, J = 7.5 Hz), 7,46 (2H, t, J = 7.5 Hz), 8,00 (1H, d, J = 8,8 Hz), 8,24 (1H, d, J = 2.6 Hz), 11,43 (1H, s), 13,47 (1H, s).

4 Phenoxy-2-(thiophene-2-carboxym is up)benzoic acid

1H-NMR (DMSO-d6) δ: 6,76 (1H, DD, J = 8,8, and 2.6 Hz), 7,17 (2H, d, J = 8.1 Hz), 7,26-7,30 (2H, m), 7,47-7,51 (2H, m), 7,72 (1H, d, J = 3.6 Hz), 7,94 (1H, d, J = 4.9 Hz), of 8.06 (1H, d, J = 8,8 Hz), compared to 8.26 (1H, d, J = 2,6 Hz).

2-(Benzylmaleimide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: the 4.65 (2H, s), of 6.66 (1H, DD, J = 8,9, and 2.3 Hz), to 7.09 (1H, d, J = 2.3 Hz), 7,18 (4H, d, J = 7,6 Hz), 7,28-7,33 (4H, m)to 7.50 (2H, m), of 7.97 (1H, d, J = 8,8 Hz), 10,87 (1H, s).

2-(Benzosulfimide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,70 (1H, DD, J = 8,8, 2.4 Hz), 6,86 (1H, d, J = 2.4 Hz), 7,05-7,07 (2H, m), 7,34 (1H, t, J = 7.5 Hz), 7,50-of 7.60 (4H, m), 7,63-of 7.70 (3H, m), of 7.90 (1H, d, J = 8,9 Hz).

2-(4-Perbenzoic)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,8, 2,5 Hz), 7,18 (2H, d, J = 7,6 Hz), 7,28 (1H, t, J = 7.2 Hz), 7,41-7,51 (4H, m), of 7.96-of 8.00 (2H, m), 8,07 (1H, d, J = 8,8 Hz), of 8.37 (1H, d, J = 2.5 Hz), KZT 12.39 (1H, s).

2-(2,4-Differentaite)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,8, and 2.6 Hz), 7,17-7,19 (2H, m), 7,26-7,31 (2H, m), 7,47-7,53 (3H, m), of 7.97 (1H, TD, J = 8,8, and 6.6 Hz), of 8.06 (1H, d, J = 8,8 Hz), 8,39 (1H, d, J = 2.6 Hz), 12,16 (1H, s).

2-(Cinnamamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,74 (1H, DD, J = 8,8, 2.4 Hz), 6,85 (1H, d, J = 15,5 Hz), 7,17 (2H, d, J = 7,6 Hz), 7,28 (1H, t, J = 7,6 Hz), 7,42-7,51 (5H, m), 7,60 (1H, d, J = 15,5 Hz), 7,72-7,74 (2H, m), 8,03 (1H, d, J = 8,8 Hz), 8,35 (1H, d, J = 2.4 Hz), 11,57 (1H, s)

2-(Cyclopropanecarboxamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 0,82-0,87 (4H, m), 1,64 is 1.70 (1H, m), 6,70 (1H, DD, J = 8,8, and 2.6 Hz), 7,12 (2H, d, J = 8,3 Hz), 7,25 (1H, is, J = 7.5 Hz), 7,46 (2H, t, J = 7.9 Hz), 8,00 (1H, d, J = 8,8 Hz), 8,17 (1H, d, J = 2.6 Hz), 11,63 (1H, s).

2-(1-Methyl-1H-pyrrol-2-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 3,86 (3H, s), x 6.15 (1H, DD, J = 4,0, 2, 7 Hz), of 6.68 (1H, DD, J = 8,9 and 2.5 Hz), 6,83 (1H, DD, J = 4.0 a, and 1.6 Hz), was 7.08 (1H, s), 7,16 (2H, d, J = 7,6 Hz), 7,26 (1H, t, J = 7,3 Hz), of 7.48 (2H, t, J = 7.9 Hz), 8,03 (1H, d, J = 8,9 Hz), with 8.33 (1H, d, J = 2.5 Hz), 12,10 (1H, s).

2-(Benzofuran-2-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,8, 2.4 Hz), 7,19 (2H, d, J = 7,6 Hz), 7,29 (1H, t, J = 7.4 Hz), 7,39 (1H, t, J = 7.5 Hz), of 7.48-7,56 (3H, m), to 7.67-7,71 (2H, m), 7,83 (1H, d, J = 7.8 Hz), of 8.09 (1H, d, J = 8,8 Hz), 8,39 (1H, d, J = 2.4 Hz), 12,74 (1H, s).

2-(1-Methyl-1H-benzotriazol-5-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 4,37 (3H, s), for 6.81 (1H, DD, J = 8,8, 2.4 Hz), 7,19 (2H, d, J = 7,6 Hz), 7,29 (1H, t, J = 7,7 Hz), 7,50 (2H, t, J = 7.9 Hz), 8,03-8,10 (3H, m), 8,40 (1H, d, J = 2.4 Hz), 8,59 (1H, s).

2-(Benzofuran-5-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6.73 x-6,77 (1H, m), 7,08-7,29 (4H, m), 7,49 (2H, t, J = 7.9 Hz), 7,78 (1H, d, J = 8.6 Hz), of 7.90 (1H, d, J = 7.9 Hz), 8,08 (1H, d, J = 8,8 Hz)to 8.14 (1H, d, J = 2.2 Hz), of 8.27 (1H, s), 8,43 (1H, d, J = 2.2 Hz).

2-(Benzothiazol-2-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,85 (1H, DD, J = 8,9 and 2.5 Hz), 7,21 (2H, d, J = 7,6 Hz), 7,30 (1H, t, J = 7.4 Hz), 7,51 (2H, t, J = 7.9 Hz), to 7.61-of 7.70 (2H, m), 8,10 (1H, d, J = 8,9 Hz), 8,18 (1H, d, J = 7,6 Hz), of 8.28 (1H, d, J = 7,6 Hz), scored 8.38 (1H, d, J = 2.5 Hz), 13,15 (1H, s), 13,71 (1H, s).

Example 98

82 mg ka is Bonita potassium and 0,047 ml benzylbromide added to the solution, containing 80 mg of methyl 2-(benzamido)-4-hydroxybenzoate in 1 ml N,N-dimethylformamide, at room temperature, and the mixture was stirred at the same temperature for 3 hours. To the reaction mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane, and the solid is separated by filtration, while receiving 75 mg of methyl 2-(benzamido)-4-(benzyloxy)benzoate as a white solid.

1H-NMR (CDCl3) δ: 3,93 (3H, s), 5,20 (2H, s), 6,72 (1H, DD, J = 9,0, 2,5 Hz), to 7.32 and 7.36 (1H, m), 7,39-7,42 (2H, m), 7,47-7,49 (2H, m), 7,51-EUR 7.57 (3H, m), 8,02 (1H, d, J = 9.0 Hz), 8,05-8,08 (2H, m), 8,76 (1H, d, J = 2.5 Hz), of 12.26 (1H, s).

Example 99

of 0.11 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to a solution containing 70 mg of methyl 2-(benzamido)-4-(benzyloxy)benzoate in a mixture of 1 ml of methanol and 2 ml of tetrahydrofuran, at room temperature, and the mixture was stirred at the same temperature for 6 hours and 30 minutes, at 40°C for 1 hour and 30 minutes and at 50°C for 2 hours. After cooling the reaction mixture to room for the Noah temperature the Solvent is evaporated under reduced pressure, and add water and diethyl ether. The aqueous layer was separated and pH 4.0 install hydrochloric acid with a concentration of 1.0 mol/l, the Solid is separated by filtration, while receiving 35 mg of 2-(benzamido)-4-(benzyloxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 5,22 (2H, s)6,86 (1H, DD, J = 8,9, 2.7 Hz), 7,34-7,38 (1H, m), 7,40-7,44 (2H, m), 7,49-7,51 (2H, m), 7,58-to 7.68 (3H, m), 7,95-of 7.97 (2H, m), 8,02 (1H, d, J = 8,9 Hz), charged 8.52 (1H, d, J = 2.7 Hz), 12,45 (1H, s), 13,30-13,70 (1H, usher.).

Example 100

of 0.13 g of potassium carbonate and 0.10 ml (2-bromacil)benzene are added to a solution containing of 0.13 g of methyl 2-(benzamido)-4-hydroxybenzoate in 2 ml of N,N-dimethylformamide, and the mixture is stirred at room temperature for 3 hours. To the reaction mixture are added 0.10 ml (2-bromacil)benzene, and the mixture was stirred at 50°C for 4 hours and at 80°C for 3 hours. After cooling the reaction mixture to room temperature, add 0.10 g of potassium carbonate and 0.10 ml (2-bromacil)benzene and the mixture is stirred at 80°C for 2 hours and 30 minutes. After cooling the reaction mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated the ri reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate

= 8:1], while receiving 0,19 g of methyl 2-(benzamido)-4-(penetrate)benzoate as a colourless oil.

1H-NMR (CDCl3) δ: 3,14 (2H, t, J = 7,1 Hz), 3,93 (3H, s), or 4.31 (2H, t, J = 7,1 Hz), only 6.64 (1H, DD, J = 9,0, 2,5 Hz), 7.23 percent-of 7.35 (5H, m), 7,50-7,56 (3H, m), to 7.99 (1H, d, J = 9.0 Hz), 8,04-8,07 (2H, m), 8,63 (1H, d, J = 2.5 Hz), 12,24 (1H, s).

Example 101

0,30 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l are added to a solution containing 0,19 g of methyl 2-(benzamido)-4-(penetrate)benzoate in a mixture of 2 ml of methanol and 2 ml of tetrahydrofuran under ice cooling, and the mixture is stirred at room temperature for 14 hours and 30 minutes. The solvent is evaporated under reduced pressure, and add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated, the solvent is evaporated under reduced pressure, and the residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 2:1], while receiving 85 mg of 2-(benzamido)-4-(penetrate)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 3,09 (2H, t, J = 6.8 Hz), the 4.29 (2H, t, J = 6.8 Hz), 6,78 (1H, DD, J = 8,9 and 2.5 Hz), 7,22-7,26 (1H, m), 7,31-7,38 (4H, m), 7,58-to 7.68 (3H, m), 7,94-of 7.96 (2H, m), of 8.00 (1H, d, J = 8,9 Hz), 8,42 (1H, d, J = 2.5 Hz), to 12.44 (1H, s).

Example 102

0,28 ml% solution of diisopropylcarbodiimide/toluene added at room temperature dropwise to the solution, containing 0.10 g of methyl 2-(benzamido)-4-hydroxybenzoate, to 0.060 ml 3-phenyl-1-propanol and 0.15 g of triphenylphosphine in 1 ml of tetrahydrofuran, and the mixture was stirred at the same temperature for 2 hours and 30 minutes. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 10:1], while receiving 45 mg of methyl 2-(benzamido)-4-(3-phenylpropoxy)benzoate as a white solid.

1H-NMR (CDCl3) δ: 2,11-to 2.18 (2H, m), and 2.83 (2H, t, J = 7,7 Hz), of 3.94 (3H, s), of 4.12 (2H, t, J = 6.2 Hz), of 6.65 (1H, DD, J = 9,0, 2.7 Hz), 7.18 in-7,31 (5H, m), 7,51-EUR 7.57 (3H, m), 8,01 (1H, d, J = 9.0 Hz), 8,05-8,07 (2H, m), to 8.62 (1H, d, J = 2.7 Hz), 12,24 (1H, s).

Example 103

0,090 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to a solution containing 45 mg of methyl 2-(benzamido)-4-(3-phenylpropoxy)benzoate in a mixture of 1 ml of methanol and 1 ml of tetrahydrofuran under ice cooling, and the mixture is stirred at room temperature for 14 hours and 30 minutes. Added dropwise 0.15 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l, and the mixture was stirred at the same temperature for 5 hours and 30 minutes. The solvent is evaporated under reduced pressure, and add water, and set pH 4.0 with hydrochloric acid with a concentration of 1.0 mol/l, the Solid is separated by filtration, is the learn to 32 mg of 2-(benzamido)-4-(3-phenylpropoxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,01-of 2.08 (2H, m), 2,77 (2H, t, J = 7,7 Hz)to 3.99 (2H, t, J = 6.2 Hz), 6,56 (1H, DD, J = 8,6, 2,5 Hz), 7,17-7,21 (1H, m), 7.24 to 7,31 (4H, m), 7,51-of 7.60 (3H, m), 7,94 (1H, d, J = 8.6 Hz), 8,03-with 8.05 (2H, m), 8.34 per (1H, d, J = 2.5 Hz).

Example 104

0,20 ml of 40% solution diisopropylsalicylic/toluene is added dropwise to a solution containing 90 mg of methyl 2-(benzamido)-4-hydroxybenzoate, a 0.035 ml of cyclohexanol and 0.10 g of triphenylphosphine in 1 ml of tetrahydrofuran, at room temperature, and the mixture was stirred at the same temperature for 5 hours. To the reaction mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 10:1], while receiving 36 mg of methyl 2-(benzamido)-4-(cyclohexyloxy)benzoate as a white solid.

1H-NMR (CDCl3) δ: 1.30 and for 1.49 (4H, m), 1,54-of 1.64 (2H, m), 1.77 in-to 1.87 (2H, m), 1,98-2,07 (2H, m), 3,93 (3H, s), 4,45-of 4.49 (1H, m), 6,63 (1H, DD, J = 9,0, 2.4 Hz), 7,51-7,58 (3H, m), to 7.99 (1H, d, J = 9.0 Hz), 8,05-8,07 (2H, m), 8,61 (1H, d, J = 2.4 Hz), 12,21 (1H, s).

Example 105

0,077 ml vodno the sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to the solution, containing 35 mg of methyl 2-(benzamido)-4-(cyclohexyloxy)benzoate in a mixture of 1 ml of methanol and 1 ml of tetrahydrofuran, at room temperature, and the mixture is stirred at room temperature overnight and at 40°C for 6 hours and 30 minutes. Added dropwise 0,050 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l at room temperature, and the mixture was stirred at the same temperature for 4 hours and 30 minutes. The solvent is evaporated under reduced pressure, and add water, and set the pH to 4.0 with hydrochloric acid with a concentration of 1.0 mol/l, the Solid is separated by filtration, while receiving 25 mg of 2-(benzamido)-4-(cyclohexyloxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,20-1,60 (6H, m), 1,68-of 1.78 (2H, m), 1,92 is 2.00 (2H, m), 4,32-4,39 (1H, m), 6,59 (1H, DD, J = 8,7, 2.4 Hz), 7,52-to 7.59 (3H, m), to 7.93 (1H, d, J = 8.7 Hz), 8,01-8,03 (2H, m), with 8.33 (1H, d, J = 2,4 Hz).

Example 106

0.31 g of iron powder are added to a solution containing of 0.53 g of methyl-2-nitro-4-(phenoxymethyl)benzoate in a mixture of 5.3 ml of methanol and 1.6 ml of acetic acid, and the resulting mixture is refluxed for 3 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and a saturated aqueous solution of sodium bicarbonate, and the insoluble matter is removed by filtering the. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is dissolved in 5.3 ml of methylene chloride, and cooled with ice successively added 0.51 ml of triethylamine and 0.26 ml of benzoyl chloride, and the mixture is stirred at room temperature for 15 hours. The solvent is evaporated under reduced pressure and the obtained residue is added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and washed with saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. To the resulting solution was added hexane and diisopropyl ether and the solid is separated by filtration, thus obtaining 0.31 g of methyl 2-(benzamido)-4-(phenoxymethyl)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 3.97 (3H, s)to 5.17 (2H, s), 6,95-to 7.00 (3H, m), 7,25-7,31 (3H, m), 7,54-7,58 (3H, m), 8,05-8,07 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 9,04 (1H, d, J = 1.2 Hz), 12,10 (1H, s).

Example 107

0.51 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to a solution containing 0.31 g of methyl 2-(benzamido)-4-(pheno is simetal)benzoate in a mixture of 3 ml of methanol and 3 ml of tetrahydrofuran, under ice cooling, and the mixture is stirred at room temperature for 5 hours and 30 minutes. The solvent is evaporated under reduced pressure, and add water, and set the pH to 4.0 with hydrochloric acid with a concentration of 1.0 mol/l, the Solid is separated by filtration, thus obtaining 0.27 g of 2-(benzamido)-4-(phenoxymethyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 5,16 (2H, s), to 6.95 (1H, t, J = 7,3 Hz), 7,02? 7.04 baby mortality (2H, m), 7,17 (1H, DD, J = 8,0, 1.2 Hz), 7,28-to 7.32 (2H, m), 7,54-to 7.61 (3H, m), 8,00-8,02 (2H, m), with 8.05 (1H, d, J = 8.0 Hz), 8,82 (1H, d, J = 1.2 Hz).

Example 108

of 0.52 ml of triethylamine and 0.16 ml of benzoyl chloride is added to the suspension containing 0.39 g of the hydrochloride of methyl 2-amino-4-((phenylthio)methyl)benzoate 3.8 ml of methylene chloride under ice cooling, and the mixture is stirred at room temperature for 3 hours and 30 minutes. The solvent is evaporated under reduced pressure and the obtained residue is added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, the solid is separated by filtration, while receiving 0.29 grams of methyl-2-(benzamido)-4-((phenylthio)methyl)benzoate as a white solid.

1H-NMR (CDCl3) δ: 3,95 (3H, s), 4,17 (2H, s), was 7.08 (1H, DD, J = 8,3, 1,6 Hz), 7,16-7,20 (1H, m), 7.24 to 7,27 (2H, m), 7,32-7,34 (2H, m), 7,51-EUR 7.57 (3H, m), to 7.99 (1H, d, J = 8,3 Hz), 8,04-of 8.06 (2H, m), of 8.95 (1H, d, J = 1.6 Hz), 12,04 (1H, s).

Example 109

0,50 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to a solution containing 0.29 grams of methyl-2-(benzamido)-4-((phenylthio)methyl)benzoate in a mixture of 3 ml of methanol and 3 ml of tetrahydrofuran under ice cooling, and the mixture is stirred at room temperature for 5 hours. Added dropwise 0.25 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l and the mixture was stirred at the same temperature for 14 hours. The solvent is evaporated under reduced pressure, and water is added, and the pH is adjusted to 4.0 with hydrochloric acid with a concentration of 1.0 mol/l, the Solid is separated by filtration, thus obtaining 0.28 g of 2-(benzamido)-4-((phenylthio)methyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 4,24 (2H, s), of 6.99 (1H, DD, J = 7,9, 1.8 Hz), 7,15-7,19 (1H, m), 7,27-7,31 (2H, m), 7,34-7,37 (2H, m), 7,52-to 7.59 (3H, m), to 7.93 (1H, d, J = 7.9 Hz), 8,01-of 8.04 (2H, m), 8,76 (1H, d, J = 1,8 Hz).

Example 110

0.16 ml of aniline, 0.12 g of 1,1'-bis(diphenylphosphino)ferrocene, 0,057 g complex (1,1'-bis(definito the Fino)ferrocene)palladium(II)dichloride and methylene chloride and 0.17 g of tert-butoxide sodium added to the solution, containing of 0.58 g of methyl 2-(benzamido)-4-bromobenzoate in 6 ml of dioxane, and the resulting mixture is refluxed under nitrogen atmosphere for 4 hours. After cooling the reaction mixture to room temperature, add 1 ml of acetic acid, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 5:1], while receiving 0,43 g methyl-4-(aniline)-2-(benzamido)benzoate as a colourless oil.

1H-NMR (DMSO-d6) δ: 3,86 (3H, s), 6,79 (1H, DD, J = 9,0, 2.4 Hz),? 7.04 baby mortality (1H, t, J = 7,3 Hz), 7,25 (2H, d, J = 7,6 Hz), 7,35-7,39 (2H, m), to 7.59-to 7.68 (3H, m), 7,89 (1H, d, J = 9.0 Hz), 7,95-of 7.97 (2H, m), 8,55 (1H, d, J = 2.4 Hz), 9,03 (1H, s), 12,09 (1H, s).

Example 111

1 ml of 10% aqueous sodium hydroxide is added to the suspension containing 0,43 g methyl-4-(aniline)-2-(benzamido)benzoate in 4 ml of ethanol at room temperature, and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add hydrochloric acid with a concentration of 1.0 mol/l and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. To the obtained residue, add diisopropyl ether and hexane, and the solid is separated by filtration, the floor is th at that 0.36 g of 4-(aniline)-2-(benzamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,9, and 2.3 Hz), 7,03 (1H, t, J = 7,3 Hz), 7,25 (1H, d, J = 7.8 Hz), was 7.36 (2H, t, J = 7,7 Hz), EUR 7.57-to 7.67 (3H, m), of 7.90 (1H, d, J = 8,9 Hz), of 7.96 (2H, d, J = 7,1 Hz), to 8.57 (1H, d, J = 2.3 Hz), 8,97 (1H, s), 12,50 (1H, s), 12,80-13,20 (1H, usher.).

Example 112

0.16 ml of thiophenol, of 0.43 g of potassium carbonate and 0,030 g of copper iodide(I) are added to a solution containing of 0.60 g of methyl 2-(benzamido)-4-iodobenzoate in 6 ml of dimethyl ether of ethylene glycol, and the resulting mixture is refluxed under nitrogen atmosphere for 13 hours. After cooling the reaction mixture to room temperature, add hydrochloric acid with a concentration of 1.0 mol/l and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate

= 5:1], while receiving of 0.30 g of methyl 2-(benzamido)-4-(phenylthio)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: 3,88 (3H, s), to 6.95 (1H, DD, J = 8,4, 1.8 Hz), 7,50-to 7.67 (8H, m), to $ 7.91-of 7.96 (3H, m), 8,51 (1H, d, J = 1,8 Hz), 11,73 (1H, s).

Example 113

0.4 ml of 10% aqueous sodium hydroxide is added to the suspension containing of 0.30 g of methyl 2-(benzamido)-4-(phenylthio)benzoate in 6 ml of ethanol at room temperature, and the resulting mixture is boiled with milk products is the first refrigerator for 1 hour. After cooling the reaction mixture to room temperature, add hydrochloric acid with a concentration of 1.0 mol/l and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. To the obtained residue, add diisopropyl ether and hexane, and the solid is separated by filtration, thus obtaining 0.28 g of 2-(benzamido)-4-(phenylthio)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,92 (1H, DD, J = 8,4, 1.8 Hz), 7,47-to 7.67 (8H, m), of 7.90-a 7.92 (2H, m), of 7.97 (1H, d, J = 8,4 Hz), 8,63 (1H, d, J = 1,8 Hz), 12,25 (1H, s).

Example 114

0.15 ml of triethylamine and 0,068 ml benzylmercaptan added to the suspension containing 0.20 g of methyl 2-(benzamido)-4-iodobenzoate, 36 mg of 1,1'-bis(diphenylphosphino)ferrocene and 24 mg of Tris(dibenzylideneacetone)diplegia(0) in 2 ml of toluene, and the mixture is stirred under nitrogen atmosphere at 80°C for 2 hours. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 10:1], while receiving 0.16 g of methyl 2-(benzamido)-4-(benzylthio)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 3.94 (3H, s), or 4.31 (2H, s), to 6.95 (1H, DD, J = 8,5, 2.0 Hz), 7.24 to 7,27 (1H, m), 7,30-7,34 (2H, m), 7,44-7,46 (2H, m), 7,51-EUR 7.57 (3H, m), 7,2 (1H, d, J = 8.5 Hz), 8,04-8,07 (2H, m), 9,03 (1H, d, J = 2.0 Hz), 12,12 (1H, s).

Example 115

of 0.43 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l is added dropwise to a solution containing 0.16 g of methyl 2-(benzamido)-4-(benzylthio)benzoate in a mixture of 1.5 ml of methanol and 1.5 ml of tetrahydrofuran under ice cooling, and the mixture is stirred at room temperature for 18 hours. The solvent is evaporated under reduced pressure, and add water, and set the pH to 4.0 with hydrochloric acid with a concentration of 1.0 mol/l, the Solid is separated by filtration, thus obtaining 0.14 g of 2-(benzamido)-4-(benzylthio)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 4,37 (2H, s), to 7.15 (1H, DD, J = 8,5, 2.0 Hz), 7.24 to 7,28 (1H, m), 7,31-to 7.35 (2H, m), of 7.48 (2H, d, J = 7,3 Hz), 7,58-to 7.68 (3H, m), 7,94-of 7.97 (3H, m), 8,77 (1H, d, J = 2.0 Hz), 12,30 (1H, s).

Example 116

53 mg of Tris(dibenzylideneacetone)diplegia(0) and 0.17 g of tert-butoxide sodium are added to a solution containing 0.50 g of tert-butyl 2-(benzamido)-4-iodobenzoate, 0.25 ml 3-phenylpropylamine and 36 mg of rat-2,2'-bis(diphenylphosphino)-1,1-binaphthyl in 5 ml of toluene, at room temperature, and the mixture is stirred at 80°C for 7 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration, and the solvent is evaporated at below the nom pressure. The resulting residue is purified column chromatography on silica gel [eluent: hexane:ethyl acetate = 6:1], while receiving 0.11 g of tert-butyl 2-(benzamido)-4-(3-phenylpropylamine)benzoate as a brown oil.

1H-NMR (CDCl3) δ: equal to 1.59 (9H, s), 1,95-2,02 (2H, m), 2,72-2,77 (1H, m), 3.25 to be 3.29 (1H, m), 6,21 (1H, DD, J = 8,8, 2,5 Hz), 7,19-7,22 (3H, m), 7,26-to 7.32 (2H, m), 7,49-of 7.55 (3H, m), 7,82 (1H, d, J = 8,8 Hz), 8,05-8,07 (2H, m), 8,24 (1H, d, J = 2.5 Hz), to 12.44-12,46 (1H, usher.).

Example 117

The following connection receive the same manner as in example 116.

tert-Butyl 2-(benzamido)-4-((2-phenylethyl)amino)benzoate

1H-NMR (CDCl3) δ: 1,60 (9H, s), 2.93 which are 2.98 (2H, m), 3,50-3,55 (2H, m), 4,23-to 4.28 (1H, usher.), of 6.25 (1H, DD, J = 8,8, 2.4 Hz), 7.23 percent-7,27 (3H, m), 7,31-to 7.35 (2H, m), 7,50-of 7.55 (3H, m), 7,83 (1H, d, J = 8,8 Hz), 8,05-8,07 (2H, m), of 8.27 (1H, d, J = 2.4 Hz), to 12.44-12,48 (1H, usher.).

Example 118

A solution containing 0.11 g of tert-butyl 2-(benzamido)-4-((3-phenylpropyl)amino)benzoate in 1.0 ml triperoxonane acid, stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, and add ethyl acetate and water, and the pH is adjusted to 6.3 with a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To polucen the th balance add hexane and diisopropyl ether, and the solid is separated by filtration, to thereby obtain 71 mg of 2-(benzamido)-4-((3-phenylpropyl)amino)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,85-of 1.92 (2H, m), 2,68-of 2.72 (2H, m), 3,09-3,14 (2H, m), 6,33 (1H, DD, J = 9,0, 2.2 Hz), 6,83-6,86 (1H, m), 7,16-to 7.32 (5H, m), EUR 7.57-7,66 (3H, m), to 7.77 (1H, d, J = 9.0 Hz), 7,94-of 7.96 (2H, m), 8,08 (1H, d, J = the 2.2 Hz), 12,54-to 12.58 (1H, usher.), 12,65-12,74 (1H, usher.).

Example 119

The following connection receive the same manner as in example 118.

2-(Benzamido)-4-((2-phenylethyl)amino)benzoic acid

1H-NMR (DMSO-d6-D2O) δ: 2,87-only 2.91 (2H, m), 3,32-to 3.36 (2H, m), to 6.39 (1H, DD, J = 9,0, 2,1 Hz), 7,21-7,26 (1H, m), 7,32-7,33 (4H, m), EUR 7.57-7,66 (3H, m), 7,79 (1H, d, J = 9.0 Hz), 7,94-of 7.96 (2H, m), 8,11 (1H, d, J = 2.1 Hz).

Example 120

0.12 g of 4-itfinal, of 0.18 ml tributylamine and 4.2 mg of palladium acetate successively added to a solution containing 0.12 g of tert-butyl 2-(benzamido)-4-vinylbenzoate 2.4 ml of N,N-dimethylacetamide at room temperature, and the mixture is stirred under nitrogen atmosphere at 110°C for 6 hours. After cooling the reaction mixture to room temperature, add 10% aqueous citric acid solution and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution, saturated aqueous sodium thiosulfate insystem aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 1:1), while receiving 0.10 g of tert-butyl 2-(benzamido)-4-((E)-2-(4-hydroxyphenyl)vinyl)benzoate as a yellow solid.

1H-NMR (DMSO-d6) δ: of 1.56 (9H, s), 6,77-6,83 (2H, m), 7,11 (1H, d, J = 15,9 Hz), 7,27 (1H, d, J = 15,9 Hz), 7,42 (1H, d, J = 8,4 Hz), 7,50-of 7.55 (2H, m), to 7.59-of 7.69 (3H, m), 7,94 (1H, d, J = 8,4 Hz), of 7.96 shed 8.01 (2H, m), 8,68-8,72 (1H, m), 9,71 (1H, s), 11,70 (1H, s).

Examples 121, 122

Compounds shown in table 15, receive the same manner as in example 120.

Table 15
# exampleR3
121
122

tert-Butyl 2-(benzamido)-4-((E)-2-(2-hydroxyphenyl)vinyl)benzoate

1H-NMR (DMSO-d6) δ: 1.57 in (9H, s), 6,78-6,93 (2H, m), 7,10-to 7.18 (1H, m), 7,30 (1H, d, J = 16,3 Hz), 7,41 (1H, DD, J = 8,4, and 1.6 Hz), 7,58-of 7.70 (5H, m), of 7.96 (1H, d, J = 8,4 Hz), 7,98-8,02 (2H, m), 8,76 (1H, d, J = 1.6 Hz), 9,94 (1H, C)11,71 (1H, s).

tert-Butyl 2-(benzamido)-4-((E)-2-(3,5-dichlor the Nile)vinyl)benzoate

1H-NMR (DMSO-d6) δ: of 1.56 (9H, s), of 7.36 (1H, d, J = 16.4 Hz), 7,49 (1H, DD, J = 8,3, 1.2 Hz), 7,53 (1H, t, J = 1,8 Hz), 7,56-to 7.68 (4H, m), 7,82 (2H, d, J = 1.7 Hz), 7,97-8,02 (3H, m), a total of 8.74 (1H, d, J = 1.4 Hz), 11,65 (1H, s).

Example 123

0.14 g of 1-bromo-4-nitrobenzene and 0.22 ml of tributylamine and 5.2 mg of palladium acetate at room temperature are added to a solution containing 0.15 g of tert-butyl 2-(benzamido)-4-vinylbenzoate in 2.0 ml of N,N-dimethylacetamide, and the mixture is stirred under nitrogen atmosphere at 110°C for 1 hour and 20 minutes. After cooling the reaction mixture to room temperature, add 10% aqueous citric acid solution and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution, saturated aqueous sodium thiosulfate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving 0.15 g of tert-butyl 2-(benzamido)-4-((E)-2-(4-nitrophenyl)vinyl)benzoate as a yellow solid.

1H-NMR (DMSO-d6) δ: 1.57 in (9H, s), 7,50-to 7.68 (6H, m), of 7.96-8,02 (5H, m), 8,24-of 8.28 (2H, m), 8,77 (1H, d, J = 1.5 Hz), 11,64 (1H, s).

Example 124

0.10 ml of 1-bromo-4-(triptoreline)is Anzola, 0,22 ml tributylamine and 5.2 mg of palladium acetate are added to a solution containing 0.15 g of tert-butyl 2-(benzamido)-4-vinylbenzoate in 2.0 ml of N,N-dimethylacetamide at room temperature, and the mixture is stirred under nitrogen atmosphere at 110°C for 3 hours. After cooling the reaction mixture to room temperature, add 0,07 ml of 1-bromo-4-(triptoreline)benzene, 0,11 ml tributylamine and 5.2 mg of palladium acetate at room temperature, and the mixture is stirred under nitrogen atmosphere at 110°C for 2 hours. After cooling the reaction mixture to room temperature, add 10% aqueous citric acid solution and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution, saturated aqueous sodium thiosulfate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: toluene:ethyl acetate = 20:1], while receiving 0.10 g of tert-butyl 2-(benzamido)-4-((E)-2-(4-(triptoreline)phenyl)vinyl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: of 1.56 (9H, s), 7,38-the 7.43 (4H, m), 7,51 (1H, DD, J = 8,4, 1.5 Hz), to 7.59-of 7.70 (3H, m), 7,81-7,86 (2H, m), 7,95-8,02 (3H, m), a total of 8.74 (1H, d, J = 1.5 Hz), 11,66 (1H, s).

Example 125

The following connection receive the same manner as in example 124.

tert-Butyl 2-(benzamido)-4-((E)-2-(3,5-differenl)vinyl)benzoate

1H-NMR (DMSO-d6) δ: of 1.56 (9H, s), 7,18 (1H, TT, J = 9,3, 2.3 Hz), 7,37 (1H, d, J = 16.4 Hz), 7,44-rate of 7.54 (4H, m), 7,60-of 7.70 (3H, m), 7,97 shed 8.01 (3H, m), a total of 8.74 (1H, d, J = 1.4 Hz), 11,65 (1H, s).

Example 126

0.20 g of 6-bromo-2-oxoindole, and 0.40 ml of N,N-dicyclohexylamine and 18 mg of TRANS-di(µ-acetato)bis-o-(di-o-tolylphosphino)benzylpiperazine(II) are added to a solution containing 0.46 g of tert-butyl 2-(benzamido)-4-vinylbenzoate in 2.0 ml of N,N-dimethylacetamide at room temperature, and the mixture is stirred under nitrogen atmosphere at 110°C for 7 hours. After cooling the reaction mixture to room temperature, add saturated aqueous solution of sodium bicarbonate and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 1:1], while receiving 0.15 g of tert-butyl 2-(benzamido)-4-((E)-2-(2-oxoindole-6-yl)vinyl)benzoate in the form of a green solid

1H-NMR (DMSO-d6) δ: of 1.56 (9H, s), 3,50 (2H, s), 7,11 (1H, s), 7,21-7,39 (4H, m)to 7.50 (1H, DD, J = 8,3, 1.5 Hz), to 7.59-of 7.70 (3H, m), 7,95 (1H, d, J = 8,3 Hz), 7,97-8,02 (2H, m), 8,69-a total of 8.74 (1H, m), 10,50 (1H, s), 11,65 (1H, s).

Example 127

0,076 ml 3-chloresterol, 0,19 ml tributylamine, 2,9 mg of tri-tert-butylperbenzoate and 4.5 mg of palladium acetate are added to a solution containing 0.15 g of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.0 ml of N,N-dimethylacetamide at room temperature, and the mixture is stirred under nitrogen atmosphere at 110°C for 4 hours and 30 minutes. After cooling the reaction mixture to room temperature, add 0,025 ml 3-chloresterol, 2,9 mg of tri-tert-butylperbenzoate and 4.5 mg of palladium acetate at room temperature, and the mixture is stirred under nitrogen atmosphere at 110°C for 1 hour and 20 minutes. After cooling the reaction mixture to room temperature, add 10% aqueous citric acid solution and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution, saturated aqueous sodium thiosulfate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: GE is San:ethyl acetate = 10:1], while receiving 86 mg of tert-butyl 2-(benzamido)-4-((E)-2-(3-chlorophenyl)vinyl)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 1.56 (9H, s), 7,13-7,34 (5H, m), 7,40 was 7.45 (1H, m), 7,52-to 7.59 (4H, m), 8,01 (1H, d, J = 8,3 Hz), 8,06-8,11 (2H, m), 9,16 (1H, d, J = 1.7 Hz), 12,27 (1H, s).

Example 128

The suspension containing 0.17 g of tert-butyl 2-(benzamido)-4-((E)-2-(2-hydroxyphenyl)vinyl)benzoate in 3.0 ml triperoxonane acid, stirred at room temperature for 30 minutes. The solvent is evaporated under reduced pressure, added toluene, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane, and the solid is separated by filtration, thus obtaining 0.12 g of 2-(benzamido)-4-((E)-2-(2-hydroxyphenyl)vinyl)benzoic acid as a yellow solid.

1H-NMR (DMSO-d6) δ: 6,79-6,94 (2H, m), 7,10-7,19 (1H, m), 7,31 (1H, d, J = 16.6 Hz), 7,40 (1H, DD, J = 8,4, and 1.6 Hz), 7,55-of 7.70 (5H, m), 7,97-8,02 (2H, m), with 8.05 (1H, d, J = 8,4 Hz), of 8.95 (1H, d, J = 1.6 Hz), 9,94 (1H, s), of 12.26 (1H, C).

Examples 129-135

Compounds shown in table 16, receive the same manner as in example 128.

Table 16
No.
example
R3 No.
example
R3
129133
130134
131135
132

2-(Benzamido)-4-((E)-2-(4-nitrophenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,50-of 7.70 (6H, m), of 7.96-8,03 (4H, m), of 8.09 (1H, d, J = 8,3 Hz), compared to 8.26 (2H, d, J = 8,8 Hz), 8,99 (1H, d, J = 1.4 Hz), 12,23 (1H, s).

2-(Benzamido)-4-((E)-2-(3,5-differenl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,13-7,22 (1H, m), 7,38 (1H, d, J = 16.1 Hz), 7,45-of 7.70 (7H, m), of 7.96-8,02 (2H, m), 8,08 (1H, d, J = 8,3 Hz), of 8.95 (1H, s).

2-(Benzamido)-4-((E)-2-(4-(triptoreline)phenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,37-7,44 (4H, m), 7,47-7,53 (1H, m), 7,58-of 7.70 (3H, m), to 7.84 (2H, d, J = 8.6 Hz), of 7.96-8,02 (2H, m), 8,07 (1H, d, J = 8.1 Hz), of 8.95 (1H, d, J = 1.4 Hz).

2-(Benzamido)-4-((E)-2-(4-hydroxyphenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6/sub> ) δ: to 6.80 (2H, d, J = 8.5 Hz), 7,12 (1H, d, J = 16,3 Hz), 7,29 (1H, d, J = 16,3 Hz), 7,42 (1H, DD, J = 8,5, and 1.6 Hz), 7,53 (2H, d, J = 8.5 Hz), 7,58-of 7.70 (3H, m), of 7.96 shed 8.01 (2H, m), 8,03 (1H, d, J = 8.5 Hz), 8,89 (1H, d, J = 1.6 Hz), 9,72 (1H, s), 12,25 (1H, s), 13,54-13,80 (1H, usher.).

2-(Benzamido)-4-((E)-2-(2-oxoindole-6-yl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 3,50 (2H, s), 7,12 (1H, s), 7,21-7,40 (4H, m), 7,49 (1H, DD, J = 8,3, 1,4 Hz), 7,58-of 7.69 (3H, m), of 7.96-8,02 (2H, m), with 8.05 (1H, d, J = 8,3 Hz), 8,91 (1H, d, J = 1.4 Hz), 10,50 (1H, s).

2-(Benzamido)-4-((E)-2-(3-chlorophenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,32-7,51 (5H, m), 7,56-of 7.69 (4H, m), 7,81 (1H, s), 7,94-of 8.00 (2H, m), with 8.05 (1H, d, J = 8.0 Hz), 8,93 (1H, d, J = 1.2 Hz), 12,23 (1H, s).

2-(Benzamido)-4-((E)-2-(3,5-dichlorophenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,37 (1H, d, J = 16.6 Hz), 7,49 (1H, DD, J = 8,4, 1.3 Hz), 7,53 (1H, t, J = 1.9 Hz), 7,58-to 7.68 (4H, m), 7,83 (2H, d, J = 1.9 Hz), 7,97 shed 8.01 (2H, m), 8,08 (1H, d, J = 8,4 Hz), of 8.95 (1H, d, J = 1.3 Hz), 12,23 (1H, ).

Example 136

12 mg of 5% palladium on coal are added to a solution containing 60 mg of 2-(benzamido)-4-((E)-2-(2-hydroxyphenyl)vinyl)benzoic acid in a mixture of 1.5 ml of methanol and 1.5 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 3 hours and 30 minutes. To the reaction mixture are added to 6.0 mg of 5% palladium on charcoal, and the mixture is stirred in hydrogen atmosphere at room temperature for 3 hours and 20 minutes. To the reaction mixture are added to 6.0 mg of 5% palladium on charcoal, and the mixture is displaced is more in the atmosphere of hydrogen at room temperature for 2 hours and 40 minutes. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 47 mg of 2-(benzamido)-4-(2-(2-hydroxyphenyl)ethyl)benzoic acid.

1H-NMR (DMSO-d6) δ: 2,81-to 2.94 (4H, m), 6,68-6,72 (1H, m), 6,79-PC 6.82 (1H, m), 6,98 for 7.12 (3H, m), EUR 7.57-to 7.68 (3H, m), 7.95 is shed 8.01 (3H, m), 8,68 (1H, s), 9,37 (1H, s).

Examples 137-139

Compounds shown in table 17, receive the same manner as in example 136.

Table 17

2-(Benzamido)-4-(2-(3,5-differenl)ethyl)benzoic acid

1H-NMR (DMSO-d6) δ: 2.95 and 3.00 for (4H, m), 6,99-7,10 (4H, m), 7,56-to 7.68 (3H, m), 7,94-of 8.00 (3H, m), 8,65 (1H, d, J = 1.2 Hz).

2-(Benzamido)-4-(2-(4-(triptoreline)phenyl)ethyl)benzoic acid

1H-NMR (DMSO-d6) δ: 2,96 (4H, s), 6,98-7,05 (1H, m), 7.24 to 7,30 (2H, m), 7,37-7,42 (2H, m), 7,55-7,66 (3H, m), 7,93-of 8.00 (3H, m)8,64 (1H, d, J = 1.5 Hz).

2-(Benzamido)-4-(2-(4-hydroxyphenyl)ethyl)benzoic acid

1H-NMR (DMSO-d6) δ: 2,78-to 2.85 (2H, m), 2,87-2,95 (2H, m), 6,64-6,69 (2H, m), 7,02-was 7.08 (3H, m), EUR 7.57-to 7.68 (3H, m), 7,93-to 7.99 (3H, m), 8,66 (1H, d, J = 1.5 Hz), to 9.15 (1H, s), 12,23 (1H, s).

Example 140

9 mg of 5% palladium on coal are added to a solution containing 30 mg of 2-benzamido-4-((E)-2-(3-chlorophenyl)vinyl)benzoic acid in a mixture of 2.7 ml of methanol and 2.7 ml of ethyl acetate, and the mixture p is remediat in an atmosphere of hydrogen at room temperature for 3 hours. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], while receiving 2.0 mg 2 benzamido-4-(2-(3-chlorophenyl)ethyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2.91 in-3,03 (4H, m), to 7.09 (1H, DD, J = 8,2, 1.5 Hz), 7,22-to 7.35 (3H, m), 7,37-7,40 (1H, m), EUR 7.57-of 7.69 (3H, m), 7,94-8,02 (3H, m), 8,67 (1H, d, J = 1.5 Hz), 12,22 (1H, s).

Example 141

0,030 ml 2,4-dipterigena, 81 mg of cesium carbonate, 12 mg of tetrabutylammonium bromide and 19 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 40 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 1.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add 19 mg deposited on the polymer bis(acetato)triphenylphosphine(II), and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution is a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added methanol, and the solid is separated by filtration, while receiving 15 mg of 2-(benzamido)-4-((E)-2-(2,4-differenl)vinyl)benzoic acid as a brown solid.

1H-NMR (DMSO-d6) δ: 7,15-7,21 (1H, m), 7,31-7,46 (3H, m)to 7.50 (1H, DD, J = 8,3) and 1.7 Hz), 7,58-7,71 (3H, m), 7,94-8,02 (3H, m), 8,07 (1H, d, J = 8,3 Hz), 8,96 (1H, s), 12,24 (1H, s), 13,70-13,90 (1H, usher.).

Example 142

The following connection receive the same manner as in example 141.

2-(Benzamido)-4-((E)-2-(benzo[1,3]dioxol-5-yl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,07 (2H, s), to 6.95 (1H, d, J = 8.1 Hz), 7,14 (1H, DD, J = 8,3, 1.5 Hz), 7.23 percent (1H, d, J = 16.4 Hz), 7,32 (1H, d, J = 16.4 Hz), 7,41 (1H, d, J = 1.7 Hz), 7,44 (1H, DD, J = 8,3) and 1.7 Hz), 7,58-of 7.70 (3H, m), 7.95 is shed 8.01 (2H,, m), of 8.04 (1H, d, J = 8,3 Hz), of 8.90 (1H, d, J = 1.5 Hz), 12,25 (1H, s), 13,71 (1H, s).

Example 143

66 mg of 5-bromination, 0.10 g of cesium carbonate, 15 mg of tetrabutylammonium bromide and 24 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 50 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 1.0 ml of toluene, at room temperature, and the mixture AC who're asked at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add 24 mg deposited on the polymer bis(acetato)triphenylphosphine(II), and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added methanol, and the solid is separated by filtration, to thereby obtain 26 mg of 2-(benzamido)-4-((E)-2-(benzothiophen-5-yl)vinyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,41-of 7.70 (7H, m), to 7.77 (1H, DD, J = 8,5, 1.2 Hz), 7,81 (1H, d, J = 5.6 Hz), 7,97-8,10 (4H, m), 8,18 (1H, d, J = 1.0 Hz), 8,97 (1H, d, J = 1.7 Hz), of 12.26 (1H, s), 13,60-13,91 (1H, usher.).

Example 144

The following connection receive the same manner as in example 143.

2-(Benzamido)-4-((E)-2-(cinoxacin-6-yl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,58-7,72 (6H, m), 7,98-8,03 (2H, m), 8,08-813 (2H, m), 8,31 is 8.38 (2H, m), 8,91-9,02 (3H, m), 12,24 (1H, s), 13,70-13,90 (1H, usher.).

Example 145

54 mg of 3-itfinal, 81 mg of cesium carbonate, 12 mg of tetrabutylammonium bromide and 19 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 40 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 1.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add 19 mg deposited on the polymer bis(acetato)triphenylphosphine(II) and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution of 40-90% acetonitrile/0.1% of triperoxonane acid], while receiving 25 mg(benzamido)-4-((E)-2-(3-hydroxyphenyl)vinyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,70-to 6.80 (1H, m), 7.03 is-7,07 (1H, m), 7,11-to 7.15 (1H, m), 7.18 in-7,33 (3H, m), of 7.48 (1H, DD, J = 8,4, 1.5 Hz), 7,58-of 7.70 (3H, m), of 7.96-8,02 (2H, m), with 8.05 (1H, d, J = 8,4 Hz), 8,91 (1H, s), 9,50 (1H, s), 12,20-12,35 (1H, usher.), 13,65-13,85 (1H, usher.).

Example 146

The following connection receive the same manner as in example 145.

2-(Benzamido)-4-((E)-2-(2,1,3-benzothiadiazole-4-yl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,56-7,72 (4H, m), 7,80 (1H, DD, J = 8,8, 7,1 Hz), 7,87 (1H, d, J = 16.4 Hz), 7,98-8,14 (5H, m), 8,21 (1H, d, J = 16.4 Hz), 9,06 (1H, s), 12,25-12,45 (1H, usher.).

Example 147

0,030 ml 3-bromopyridine, 0.10 g of cesium carbonate, 15 mg of tetrabutylammonium bromide and 24 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 50 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 1.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add 24 mg deposited on the polymer bis(acetato)triphenylphosphine(II), and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and asystem aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution of 40-90% acetonitrile/0.1% of triperoxonane acid]. To the resulting purified substance added ethyl acetate and water, and the pH is adjusted to 6.0 with a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with water, and the solvent is evaporated under reduced pressure, thus obtaining 2,3 mg of 2-(benzamido)-4-((E)-2-(pyridin-3-yl)vinyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,39-of 7.70 (7H, m), 7,97-8,03 (2H, m), 8,08 (1H, d, J = 8,3 Hz), 8,17 (1H, dt, J = 7,9, 1.9 Hz), 8,51 (1H, DD, J = 4,6, 1.5 Hz), 8,86 (1H, d, J = 1.9 Hz), 8,96 (1H, d, J = 1.5 Hz), 12,25-12,50 (1H, usher.).

Example 148

61 mg of 5-benzofuran, 0.10 g of cesium carbonate, 15 mg of tetrabutylammonium bromide and 24 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 50 mg of tert-butyl 2-(benzamido)-4-vinylbenzoate in 1.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 24 hours. After ohla the tion of the reaction mixture to room temperature, add 24 mg deposited on the polymer bis(acetato)triphenylphosphine(II) and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], while receiving 2.4 mg of 2-(benzamido)-4-((E)-2-(benzofuran-5-yl)vinyl)benzoic acid.

1H-NMR (DMSO-d6) δ: 6,97-7,02 (1H, m), 7,35 (1H, d, J = 16,3 Hz), 7,46-7,53 (2H, m), to 7.59-7,74 (5H, m), 7,97-8,08 (5H, m), of 8.95 (1H, s), 12,29-12,47 (1H, usher.).

Example 149

0.12 g of 5-bromobenzophenone, 0.20 g of cesium carbonate, 30 mg of tetrabutylammonium bromide and 48 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 0.10 g of tert-butyl 2-(benzamido)-4-vinylbenzoate in 2.0 ml of toluene, at room temperature, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to the room temperature, add 48 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 2.4 ml of tetrahydrofuran, 0.6 ml of water, of 0.44 ml of acetic acid, of 0.42 g of sodium formate and 50 mg of 3.9% palladium on coal (complex with Ethylenediamine), and the mixture was stirred at 50°C for 12 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], while receiving 8.6 mg 2-(benzamido)-4-(2-(Ben is furan-5-yl)ethyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: to 3.02 (4H, s), 6.89 in (1H, DD, J = 2,2, 1.0 Hz), to 7.09 (1H, DD, J = 8,3) and 1.7 Hz), 7,22 (1H, DD, J = 8,3, 1,6 Hz), 7,49 (1H, d, J = 8,3 Hz), 7,53 (1H, d, J = 1.7 Hz), EUR 7.57-of 7.69 (3H, m), 7,92-of 8.00 (4H, m), 8,69 (1H, d, J = 1,6 Hz), 12,25 (1H, s), 13,54-13,79 (1H, usher.).

Example 150

by 0.055 ml of triethylamine and 0.036 ml of 4-tormentilla successively added to a solution containing 60 mg of tert-butyl 2-amino-4-(2,4-differenl)benzoate in 3.5 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture at room temperature successively added of 0.014 ml of triethylamine and a 0.012 ml 4-tormentilla, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(2,4-differenl)-2-(4-perbenzoic)benzoate.

To the obtained tert-butyl-4-(2,4-differenl)-2-(4-perbenzoic)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is dobavlaut diisopropyl ether, and the solid is separated by filtration, to thereby obtain 46 mg of 4-(2,4-differenl)-2-(4-perbenzoic)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,27 (1H, TD, J = 8,5, 2,5 Hz), of 7.36-to 7.50 (4H, m), 7,63-of 7.70 (1H, m), 8,00-8,08 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), 8,89 (1H, s), 12,24 (1H, s).

Examples 151-155

Compounds shown in table 18, receive the same manner as in example 150.

Table 18

2-(Benzo[1,3]dioxol-5-carboxamido)-4-(2,4-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,17 (2H, s), 7,13 (1H, d, J = 8.0 Hz), 7,26 (1H, TD, J = 8,5, 2,5 Hz), was 7.36 (1H, d, J = 8,3 Hz), 7,40-of 7.48 (2H, m), 7,52-EUR 7.57 (1H, m), 7,62-of 7.69 (1H, m), 8,13 (1H, d, J = 8,3 Hz), 8,91 (1H, s), 12,10 (1H, s).

2-(Benzothiazol-2-carboxamido)-4-(2,4-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: 7.24 to to 7.32 (1H, m), 7,42-to 7.50 (2H, m), to 7.61-7,73 (3H, m), 8,16-8,23 (2H, m), 8,27-8,32 (1H, m), 8,96-8,98 (1H, m), 13,03 (1H, s).

4-(2,4-Differenl)-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7.23 percent-7,31 (1H, m), 7,38-7,49 (2H, m), of 7.64-7,71 (1H, m), of 8.00 (2H, d, J = 8,3 Hz), 8,13-8,18 (3H, m), 8,88-8,89 (1H, m), 12,32 (1H, s).

4-(2,4-Differenl)-2-(4-nitrobenzamide)benzoic acid

1H-NMR (DMSO-d6) δ: 7,22-to 7.32 (1H, m), 7,40-7,49 (2H, m), of 7.64-7,73 (1H, m), 8,13-8,23 (3H, m), 8,42-of 8.47 (2H, m), 8,84 cent to 8.85 (1H, m), of 12.33 (1H, s).

2 Cinnamamide-4-(2,4-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,92 (1H, d, J = 15,9 Hz), 7,26 (1H, t is, J = 8,4, and 2.3 Hz), was 7.36 (1H, dt, J = 8,2) and 1.7 Hz), 7,39-7,49 (4H, m), 7,60-of 7.70 (2H, m), 7,71-7,79 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 8,84 (1H, s), 11,40 (1H, s).

Example 156

0,056 ml of triethylamine and 0.036 ml of 4-tormentilla successively added to a solution containing 60 mg of tert-butyl 2-amino-4-((E)-2-(3-methoxyphenyl)vinyl)benzoate in 3.5 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture sequentially at ambient temperature type of 0.014 ml of triethylamine and a 0.012 ml 4-tormentilla, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(4-perbenzoic)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoate.

To the obtained tert-butyl 2-(4-perbenzoic)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated fil the management, while receiving 45 mg of 2-(4-perbenzoic)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 3,82 (3H, s), make 6.90 (1H, DD, J = 7,9, and 2.3 Hz), 7.24 to the 7.43 (4H, m), 7,43-7,52 (3H, m), 8,02-8,08 (3H, m), 8,89 (1H, s), 12,22 (1H, s).

Examples 157-161

Compounds shown in table 19, receive the same manner as in example 156.

Table 19

2-(Benzo[1,3]dioxol-5-carboxamido)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 3,82 (3H, s), 6,17 (2H, s), 6,88-6,91 (1H, m), 7,13 (1H, d, J = 8.1 Hz), 7.23 percent-the 7.43 (5H, m), 7,44-7,49 (2H, m), 7,56 (1H, DD, J = 8,3, 1.8 Hz), of 8.04 (1H, d, J = 8,3 Hz), of 8.90 (1H, s), 12,10 (1H, s), 13,60-13,85 (1H, usher.).

2-(Benzothiazol-2-carboxamido)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: a 3.83 (3H, s), 6,88-6,94 (1H, m), 7,25-7,46 (5H, m), 7,54 (1H, d, J = 7.9 Hz), to 7.61-7,73 (2H, m), of 8.09 (1H, d, J = 7.9 Hz), to 8.20 (1H, d, J = 7.8 Hz), 8,30 (1H, d, J = 7.8 Hz), 8,96 (1H, s).

4-((E)-2-(3-Methoxyphenyl)vinyl)-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 3,82 (3H, s), 6,88-6,92 (1H, m), 7.24 to 7,44 (5H, m), 7,39 (2H, d, J = 4.9 Hz), 7,52 (1H, DD, J = 8,3, 1,4 Hz), 8,01 (2H, d, J = 8,2 Hz), 8,07 (1H, d, J = 8,3 Hz), 8,18 (2H, d, J = 8,2 Hz), 8,88 (1H, d, J = 1.4 Hz), 12,30 (1H, s).

4-((E)-2-(3-Methoxyphenyl)vinyl)-2-(4-nitrobenzamide)benzoic acid

1H-NMR (DMSO-d6) δ: 3,82 (3H, s), make 6.90 (1H, DD, J = 7,7, 1.8 Hz), 7,20-7,46 (5H, m), 7,54 (1H, DD, J = 8,3, 1,6 Hz), 8,07 (1H, d, J = 8,3 Hz), 8.17-a 8,24 (2H, m), 8,46 (2H, d, J = 8,8 Hz), cent to 8.85 (1H,d, J = 1,6 Hz), 12,32 (1H, s).

2 Cinnamamide-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid

1H-NMR (DMSO-d6) δ: 3,82 (3H, s), 6,86-of 6.96 (2H, m), 7,22-7,40 (5H, m), 7,42-to 7.50 (4H, m), the 7.65 (1H, d, J = 15.6 Hz), 7,72-7,79 (2H, m), 8,01 (1H, d, J = 8,3 Hz), 8,82 (1H, s), 11,38 (1H, s).

Example 162

by 0.055 ml of triethylamine and 0.036 ml of 4-tormentilla successively added to a solution containing 60 mg of tert-butyl 2-amino-4-(3-chlorophenyl)benzoate in 3.5 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture sequentially at ambient temperature type of 0.014 ml of triethylamine and a 0.012 ml 4-tormentilla, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(3-chlorophenyl)-2-(4-perbenzoic)benzoate.

To the obtained tert-butyl 4-(3-chlorophenyl)-2-(4-perbenzoic)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, and to polucen the th balance add diisopropyl ether, and the solid is separated by filtration, to thereby obtain 59 mg of 4-(3-chlorophenyl)-2-(4-perbenzoic)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,46 (2H, t, J = 8,8 Hz), 7,51 to 7.62 (3H, m), 7.68 per-7,74 (1H, m), 7,76 (1H, s), with 8.05 (2H, DD, J = 8,8, 5,4 Hz)to 8.14 (1H, d, J = 8,3 Hz), 9,01 (1H, d, J = 1.7 Hz), 12,20 (1H, s).

Examples 163-167

Compounds shown in table 20, receive the same manner as in example 162.

Table 20

2-(Benzo[1,3]dioxol-5-carboxamido)-4-(3-chlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,17 (2H, s), 7,14 (1H, d, J = 8,3 Hz), was 7.45 (1H, d, J = 1.7 Hz), 7,51-of 7.60 (4H, m), of 7.70 (1H, d, J = 7,6 Hz), 7,76 (1H, s), 8,13 (1H, d, J = 8,3 Hz), of 9.02 (1H, d, J = 1.7 Hz), 12,13 (1H, s).

2-(Benzothiazol-2-carboxamido)-4-(3-chlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,52-7,80 (7H, m), 8,15-8,23 (2H, m), 8,30 (1H, d, J = 8.0 Hz), 9,07 (1H, d, J = 1.7 Hz), 13,03 (1H, s).

4-(3-Chlorophenyl)-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,52 to 7.62 (3H, m), 7,71 (1H, dt, J = 7,5, and 1.6 Hz), to 7.77 (1H, t, J = 1.6 Hz), 8,01 (2H, d, J = 8,2 Hz), 8,15 (1H, d, J = 8,3 Hz), 8,18 (2H, d, J = 8,2 Hz), 8,99 (1H, d, J = 2.0 Hz), 12,30 (1H, s).

4-(3-Chlorophenyl)-2-(4-nitrobenzamide)benzoic acid

1H-NMR (DMSO-d6) δ: 7,51-7,66 (3H, m), 7,71 (1H, d, J = 7,6 Hz), 7,78 (1H, s), 8,15 (1H, d, J = 8,3 Hz), 8,21 (2H, d, J = 8,8 Hz), to 8.45 (2H, d, J = 8,8 Hz), 8,96 (1H, d, J = 1.5 Hz), 12,32-12,42 (1H, usher.).

4-(3-Chlorophenyl)-2-cinnamomeiventris acid

1H-NMR (DMSO-d ) δ: 6,94 (1H, d, J = 15.6 Hz), 7,40-7,49 (3H, m), 7,50-of 7.60 (3H, m), 7,62-7,79 (5H, m), 8,10 (1H, d, J = 8,3 Hz), 8,96 (1H, d, J = 1.7 Hz), 11,40 (1H, s).

Example 168

0,054 ml of triethylamine and 0.035 ml of 4-tormentilla successively added to a solution containing 60 mg of tert-butyl 2-amino-4-(benzofuran-2-yl)benzoate in 3.5 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 5 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(benzofuran-2-yl)-2-(4-perbenzoic)benzoate.

To the obtained tert-butyl 4-(benzofuran-2-yl)-2-(4-perbenzoic)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 52 mg of 4-(benzofuran-2-yl)-2-(4-perbenzoic)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,28-to 7.35 (1H, m), 7,38-7,42 (1H, m), 7,44-7,52 (2H, m), 7,63 (1H, s), 7,70-7,81 (3H, m), 8,04-8,11 (2H, m), 8,16 (H, d, J = 8,3 Hz), 9,26-9,27 (1H, m), of 12.26 (1H, s).

Examples 169-172

Compounds shown in table 21, receive the same manner as in example 168.

Table 21

2-(Benzo[1,3]dioxol-5-carboxamido)-4-(benzofuran-2-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,18 (2H, s), to 7.15 (1H, d, J = 8.0 Hz), 7,28-to 7.35 (1H, m), 7,37-7,44 (1H, m), 7,47 (1H, d, J = 1.7 Hz), 7,58 (1H, DD, J = 8,2) and 1.7 Hz), a 7.62 (1H, s), 7,70-7,79 (3H, m), 8,15 (1H, d, J = 8,2 Hz), 9.28 are (1H, d, J = 1.7 Hz), 12,18 (1H, s).

4-(Benzofuran-2-yl)-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,29-to 7.35 (1H, m), 7,39-the 7.43 (1H, m), 7,63 (1H, d, J = 0.9 Hz), 7,70-7,76 (2H, m), 7,80 (1H, DD, J = 8,4, 1.7 Hz), 8,01 (2H, d, J = 8,2 Hz), 8,15 (1H, d, J = 8,4 Hz), 8,19 (2H, d, J = 8,2 Hz), 9,24-9,26 (1H, m), 12,37 (1H, s).

4-(Benzofuran-2-yl)-2-(4-nitrobenzamide)benzoic acid

1H-NMR (DMSO-d6) δ: 7,29-7,34 (1H, m), 7,37-the 7.43 (1H, m), 7,63 (1H, s), 7,70-7,74 (2H, m), 7,81 (1H, DD, J = 8,4, 1.7 Hz), 8,16 (1H, d, J = 8,4 Hz), by 8.22 (2H, d, J = 8,8 Hz), to 8.45 (2H, d, J = 8,8 Hz), of 9.21 (1H, d, J = 1.7 Hz), 12,40 (1H, s).

4-(Benzofuran-2-yl)-2-(cinnamamide)benzoic acid

1H-NMR (DMSO-d6) δ: 6,95 (1H, d, J = 15,4 Hz), 7,29-7,34 (1H, m), 7,37 is 7.50 (4H, m), 7,60 (1H, s), 7,66-7,81 (6H, m)to 8.12 (1H, d, J = 8,3 Hz), of 9.21 (1H, d, J = 1.7 Hz), 11,47 (1H, s).

Example 173

0,044 ml of triethylamine and 0,028 ml 4-tormentilla successively added to a solution containing 60 mg of tert-butyl 2-amino-4-(4-(tert-butoxycarbonyl)oxyphenyl)benzoate in 3.5 ml methylthio the IDA, at room temperature, and the mixture was stirred at the same temperature for 5 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(4-(tert-butoxycarbonyl)oxyphenyl)-2-(4-perbenzoic)benzoate.

To the obtained tert-butyl 4-(4-(tert-butoxycarbonyl)oxyphenyl)-2-(4-perbenzoic)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 49 mg of 4-(4-hydroxyphenyl)-2-(4-perbenzoic)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,92 (2H, d, J = 8,8 Hz), 7,42-to 7.50 (3H, m), 7,58 (2H, d, J = 8,8 Hz), 8,00-8,10 (3H, m), 8,98 (1H, d, J = 1.7 Hz), 9,79 (1H, s), 12,24 (1H, s).

Examples 174-178

Compounds shown in table 22, receive the same manner as in example 173.

Table 22

2-(Benzo[1,3]dioxol-5-carboxamido)-4-(4-hydroxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,17(2H, C)6,91 (2H, d, J = 8,8 Hz), 7,13 (1H, d, J = 8,4 Hz), 7,42 (1H, DD, J = 8,4, 1.8 Hz), was 7.45 (1H, d, J = 1,8 Hz), 7,52-to 7.61 (3H, m), 8,07 (1H, d, J = 8,3 Hz), 8,99 (1H, d, J = 1.6 Hz), 9,78 (1H, s), 12,14 (1H, s), 13,55-13,85 (1H, usher.).

2-(Benzothiazol-2-carboxamido)-4-(4-hydroxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,93 (2H, d, J = 8.7 Hz), 7,52 (1H, DD, J = 8,4, 1.8 Hz), 7,58-7,72 (4H, m), 8,11 (1H, d, J = 8,4 Hz), 8.17-a 8,23 (1H, m), 8,28-of 8.33 (1H, m), 9,03 (1H, d, J = 1.9 Hz), 9,81 (1H, s), of 13.05 (1H, s), 13,60-14,00 (1H, user.).

4-(4-Hydroxyphenyl)-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,90-of 6.96 (2H, m), of 7.48 (1H, DD, J = 8,5, 1.8 Hz), 7,56-7,63 (2H, m), 8,01 (2H, d, J = 8,2 Hz), of 8.09 (1H, d, J = 8.5 Hz), 8,17 (2H, d, J = 8,2 Hz), 8,97 (1H, d, J = 1,8 Hz), 9,70-9,90 (1H, usher.), 12,34 (1H, s).

4-(4-Hydroxyphenyl)-2-(4-nitrobenzamide)benzoic acid

1H-NMR (DMSO-d6) δ: 6.90 to-6,95 (2H, m), 7,49 (1H, DD, J = 8,3, 1.9 Hz), 7,56 to 7.62 (2H, m), of 8.09 (1H, d, J = 8,3 Hz), 8.17-a 8,23 (2H, m), to 8.41-8,48 (2H, m), to 8.94 (1H, d, J = 1.9 Hz), 9,80 (1H, s), 12,35 (1H, s).

2-(Cinnamamide)-4-(4-hydroxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,88-to 6.95 (3H, m), 7,38-of 7.48 (4H, m), 7,53-to 7.59 (2H, m), the 7.65 (1H, d, J = 15.6 Hz), 7,72 for 7.78 (2H, m), of 8.04 (1H, d, J = 8.6 Hz), of 8.92 (1H, d, J = 2.0 Hz), made up 9.77 (1H, s)11,43 (1H, s), 13,45-13,70 (1H, usher.).

Example 179

0,054 ml of triethylamine and 0,034 ml 4-tormentilla successively added to a solution containing 60 mg of tert-butyl 2-amino-4-(benzo[1,3]dioxol-5-yl)benzoate in 3.5 ml of methylene chloride, at room temperature, and the mixture was stirred at the aka the same temperature for 5 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(benzo[1,3]dioxol-5-yl)-2-(4-perbenzoic)benzoate.

To the obtained tert-butyl 4-(benzo[1,3]dioxol-5-yl)-2-(4-perbenzoic)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether and the solid is separated by filtration, to thereby obtain 39 mg of 4-(benzo[1,3]dioxol-5-yl)-2-(4-perbenzoic)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,11 (2H, s), was 7.08 (1H, d, J = 8.0 Hz), 7.23 percent (1H, DD, J = 8,0, 1.9 Hz), 7,29 (1H, d, J = 1.9 Hz), 7,43-to 7.50 (3H, m), 8,00-8,16 (3H, m), 8,96 (1H, d, J = 1.9 Hz), 12,20 (1H, s).

Examples 180-183

Compounds shown in table 23, receive the same manner as in example 179.

Table 23

2-(Benzo[1,3]dioxol-5-carboxamido)-4-(benzo[1,3]dioxol-5-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,11 (2H, s), 6,17 (2H, s), 7,07 (1H, d, J = 8,2 Hz), 7,13 (1H, d, J = 8,2 Hz), 7.23 percent (1H, DD, J = 8,2, 1.9 Hz), 7,28 (1H, d, J = 1.9 Hz), 7,42-7,47 (2H, is), at 7.55 (1H, DD, J = 8,3, 1.9 Hz), 8,07 (1H, d, J = 8,3 Hz), 8,97 (1H, d, J = 2.0 Hz), 12,12 (1H, s), 13,65-13,85 (1H, usher.).

4-(Benzo[1,3]dioxol-5-yl)-2-(benzothiazole-2-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,12 (2H, s), to 7.09 (1H, d, J = 8.0 Hz), 7,22-7,28 (1H, m), 7,31 (1H, d, J = 1.5 Hz), 7,51-EUR 7.57 (1H, m), 7,60 to 7.75 (2H, m)to 8.12 (1H, d, J = 7.8 Hz), 8,16-8,24 (1H, m), 8,30 (1H, d, J = 7.8 Hz), of 9.02 (1H, s), 13,02 (1H, s).

4-(Benzo[1,3]dioxol-5-yl)-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,11 (2H, s), was 7.08 (1H, d, J = 8.1 Hz), 7,24 (1H, DD, J = 8,1, 1.8 Hz), 7,30 (1H, d, J = 1,8 Hz), to 7.50 (1H, DD, J = 8,4, 1.9 Hz), 8,01 (2H, d, J = 8,3 Hz), of 8.09 (1H, d, J = 8,4 Hz), 8,17 (2H, d, J = 8,3 Hz), 8,95 (1H, d, J = 1.9 Hz), 12,35 (1H, s).

4-(Benzo[1,3]dioxol-5-yl)-2-(cinnamamide)benzoic acid

1H-NMR (DMSO-d6) δ: 6,11 (2H, s), 6,92 (1H, d, J = 15.6 Hz), 7,07 (1H, d, J = 8.1 Hz), 7,21 (1H, DD, J = 8,1, 1.9 Hz), 7,27 (1H, d, J = 1.9 Hz), 7,41-7,49 (4H, m), the 7.65 (1H, d, J = 15.6 Hz), 7,72 for 7.78 (2H, m), of 8.04 (1H, d, J = 8,3 Hz), of 8.90 (1H, d, J = 2.0 Hz), 11,43 (1H, s).

Example 184

1.7 ml of methylene chloride, and 1.0 μl of N,N-dimethylformamide and 0.025 ml of oxalicacid add to 41 mg of 2,3-dimethylbenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 50 mg of tert-butyl 2-amino-4-(benzofuran-2-yl)benzoate in a mixture of 2.8 ml of methylene chloride and 0.36 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction sm is si add saturated aqueous solution of sodium bicarbonate, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(benzofuran-2-yl)-2-(2,3-dimethylbenzamide)benzoate.

To the obtained tert-butyl 4-(benzofuran-2-yl)-2-(2,3-dimethylbenzamide)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added ethyl acetate, and the solid is separated by filtration, while receiving 15 mg of 4-(benzofuran-2-yl)-2-(2,3-dimethylbenzamide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 2.33 (3H, s)to 2.35 (3H, s), 7,25 (1H, t, J = 7,6 Hz), 7,29-7,46 (4H, m), of 7.64 (1H, s), 7,71-7,76 (2H, m), 7,78 (1H, DD, J = 8,3) and 1.7 Hz), 8,13 (1H, d, J = 8,3 Hz), 9,26-9.28 are (1H, m), 11,65 (1H, s).

Example 185

The following connection receive the same manner as in example 184.

4-(Benzofuran-2-yl)-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,39-6,41 (2H, m), 7,30-the 7.43 (2H, m), to 7.59-7,63 (2H, m), the 7.65 (1H, s), 7,71-7,76 (1H, m), 7,83 (1H, DD, J = 8,4, and 1.6 Hz), 8,17 (1H, d, J = 8,4 Hz), 8,48-8,51 (1H, m), 9,01 (1H, d, J = 1.5 Hz), 9,18 (1H, d, J = 2,4 Hz), which 9.22 (1H, d, J = 1.4 Hz), of 12.33 (1H, s).

Example 186

<> 1.7 ml of methylene chloride, and 1.0 μl of N,N-dimethylformamide and 0.025 ml of oxalicacid successively added to 41 mg of 2,3-dimethylbenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 62 mg of tert-butyl 2-amino-4-(4-(tert-butoxycarbonyl)oxyphenyl)benzoate in a mixture of 2.8 ml of methylene chloride and 0.36 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2,3-dimethylbenzamide)-4-(4-(tert-butoxycarbonyl)oxyphenyl)benzoate.

To the obtained tert-butyl 2-(2,3-dimethylbenzamide)-4-(4-(tert-butoxycarbonyl)oxyphenyl)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added ethyl acetate, and the solid is separated by filtration, thus obtaining 20 mg of 2-(2,3-dimethylbenzamide)-4-(4-hydroxyphenyl)benzoic acid as a white solid.

1 H-NMR (DMSO-d6) δ: 2,31 (3H, s), of 2.33 (3H, s), 6.90 to-6,95 (2H, m), 7.23 percent (1H, t, J = 7.5 Hz), 7,34 (1H, d, J = 7.5 Hz), 7,40 (1H, d, J = 7.5 Hz), 7,44 (1H, DD, J = 8,3) and 1.7 Hz), 7,56-of 7.60 (2H, m), with 8.05 (1H, d, J = 8,3 Hz), 8,97-8,99 (1H, m), 9,75-9,85 (1H, usher.), 11,59 (1H, s), 13,40-13,70 (1H, usher.).

Example 187

The following connection receive the same manner as in example 186.

4-(4-Hydroxyphenyl)-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMCO-d6) δ: 6,39 (2H, s), 6,93 (2H, d, J = 8.5 Hz), to 7.50 (1H, DD, J = 8,4, 1.3 Hz), 7,56-the 7.65 (4H, m), of 8.09 (1H, d, J = 8.0 Hz), of 8.47 (1H, s), 8,93-8,99 (2H, m), 9,17 (1H, d, J = 2.2 Hz), 9,80 (1H, s), 12,31 (1H, s).

Example 188

1.7 ml of methylene chloride, and 1.0 μl of N,N-dimethylformamide and 0.025 ml of oxalicacid successively added to 41 mg of 2,3-dimethylbenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 50 mg of tert-butyl 2-amino-4-(benzo[1,3]dioxol-5-yl)benzoate in a mixture of 2.8 ml of methylene chloride and 0.36 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent:hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(benzo[1,3]dioxol-5-yl)-2-(2,3-dimethylbenzamide)benzoate.

To the obtained tert-butyl 4-(benzo[1,3]dioxol-5-yl)-2-(2,3-dimethylbenzamide)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added methanol, and the solid is separated by filtration, to thereby obtain 31 mg of 4-(benzo[1,3]dioxol-5-yl)-2-(2,3-dimethylbenzamide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), of 2.33 (3H, s), 6,11 (2H, s), was 7.08 (1H, d, J = 8.1 Hz), 7,20-7,27 (2H, m), 7,29 (1H, d, J = 1.7 Hz), 7,34 (1H, d, J = 7,3 Hz), 7,40 (1H, d, J = 7,3 Hz), 7,46 (1H, DD, J = 8,4, 1.8 Hz), with 8.05 (1H, d, J = 8,4 Hz), 8,93-9,00 (1H, usher.), 11,58 (1H, s), 13,55-of 13.75 (1H, usher.).

Example 189

1.7 ml of methylene chloride, and 1.0 μl of N,N-dimethylformamide and 0.025 ml of oxalicacid successively added to 41 mg of 2,3-dimethylbenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 49 mg of tert-butyl 2-amino-4-(2,4-differenl)benzoate in a mixture of 2.8 ml of methylene chloride and 0.36 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic is the third layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(2,4-differenl)-2-(2,3-dimethylbenzamide)benzoate.

To the obtained tert-butyl-4-(2,4-differenl)-2-(2,3-dimethylbenzamide)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added methanol, and the solid is separated by filtration, while receiving 17 mg of 4-(2,4-differenl)-2-(2,3-dimethylbenzamide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), 2,31 (3H, s), 7,21-7,30 (2H, m), 7,31-7,49 (4H, m), 7,63-of 7.70 (1H, m), 8,11 (1H, d, J = 8.0 Hz), 8,89 (1H, s), 11,58 (1H, s).

Example 190

The following connection receive the same manner as in example 189.

4-(2,4-Differenl)-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,39 (2H, t, J = 2.2 Hz), 7,28 (1H, TD, J = 8,7, 2.2 Hz), 7,42-of 7.48 (2H, m), to 7.59 (2H, t, J = 2.2 Hz), to 7.68 (1H, TD, J = 8,7, and 6.6 Hz), 8,16 (1H, d, J = 8.0 Hz), 8,46 (1H, t, J = 2.2 Hz), cent to 8.85 (1H, d, J = 1.4 Hz), 8,97 (1H, d, J = 1.7 Hz), 9,17 (1H, d, J = 2.3 Hz), 12,22 (1H, s).

Example 191

1.7 ml of methylene chloride, and 1.0 μl of N,N-dimethylformamide and 0.025 of macclelland successively added to 41 mg of 2,3-dimethylbenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 52 mg of tert-butyl 2-amino-4-((E)-2-(3-methoxyphenyl)vinyl)benzoate in a mixture of 2.8 ml of methylene chloride and 0.36 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2,3-dimethylbenzamide)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoate.

To the obtained tert-butyl 2-(2,3-dimethylbenzamide)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added methanol, and the solid is separated by filtration, while receiving 15 mg of 2-(2,3-dimethylbenzamide)-4-((E)-2-(3-methoxyphenyl)vinyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), of 2.33 (3H, s), 3,82 (3H, s), 6,88-6,91 (1H, m), 7,21-7,52 (9H, m), 8,02 (1H, d, J = 8,3 Hz), 8,89 (1H, s), 11,59 (1H, s), 13,60 (1H, s).

Example 192

The following is connected to the th receive in the same way, as in example 191.

4-((E)-2-(3-Methoxyphenyl)vinyl)-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: a 3.83 (3H, s)6,40 (2H, t, J = 2.2 Hz), 6,91 (1H, DDD, J = 8.0 a, 2,5, 0.9 Hz), 7,25-7,44 (5H, m), 7,53 (1H, DD, J = 8,3, 1,6 Hz), to 7.59 (2H, t, J = 2.2 Hz), 8,07 (1H, d, J = 8,3 Hz), 8,45-of 8.47 (1H, m), 8,84 (1H, d, J = 1.7 Hz), 8,99 (1H, d, J = 1.6 Hz), 9,17 (1H, d, J = 2.4 Hz), 12,20-to 12.35 (1H, usher.).

Example 193

1.7 ml of methylene chloride, and 1.0 μl of N,N-dimethylformamide and 0.025 ml of oxalicacid successively added to 41 mg of 2,3-dimethylbenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 49 mg of tert-butyl 2-amino-4-(3-chlorophenyl)benzoate in a mixture of 2.8 ml of methylene chloride and 0.36 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-(3-chlorophenyl)-2-(2,3-dimethylbenzamide)benzoate.

To the obtained tert-butyl 4-(3-chlorophenyl)-2-(2,3-dimethylbenzamide)benzoate add 10 ml triperoxonane acid, and the mixture is stirred the ri room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added methanol, and the solid is separated by filtration, while receiving 32 mg of 4-(3-chlorophenyl)-2-(2,3-dimethylbenzamide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), of 2.33 (3H, s), from 7.24 (1H, t, J = 7.5 Hz), 7,34 (1H, d, J = 7.5 Hz), 7,41 (1H, d, J = 7.5 Hz), 7,52-to 7.61 (3H, m), 7,69 for 7.78 (2H, m), 8,11 (1H, d, J = 8,3 Hz), 9,01 (1H, s), 11,58 (1H, s), 13,60-13,90 (1H, usher.).

Examples 194, 195

Compounds shown in table 24, we get in the same way as in example 193.

Table 24

4-(3-Chlorophenyl)-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,39 (2H, t, J = 2.2 Hz), 7,52-to 7.64 (5H, m), 7,72 (1H, dt, J = 7,6, and 1.6 Hz), 7,78 (1H, t, J = 1.6 Hz), 8,15 (1H, d, J = 8,3 Hz), 8,46-8,48 (1H, m), 8,96 (1H, d, J = 1.7 Hz), 8,99 (1H, d, J = 1.7 Hz), 9,17 (1H, d, J = 2.7 Hz), 12,23 (1H, s).

1H-NMR (DMSO-d6) δ: 2,32 (3H, s), 7,39 (2H, d, J = 8.5 Hz), 7,52 to 7.62 (3H, m), 7.68 per-7,74 (1H, m), to 7.77 (1H, s), 8,03 (2H, d, J = 8.5 Hz), 8,14 (1H, d, J = 8,3 Hz), 9,03 (1H, d, J = 1.7 Hz), 12,23 (1H, s).

Example 196

7,6 mg of potassium carbonate are added to a solution containing 15 mg of 2-(4-acetoxybenzoic)-4-(3-chlorophenyl)benzoic acid in a mixture of 0.5 ml of methanol and 0.5 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 2 hours. After removing insoluble substances by filtration, add 10% wagnerstr citric acid, and the solid is separated by filtration, while receiving 10 mg of 4-(3-chlorophenyl)-2-(4-hydroxybenzamide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,91-6,97 (2H, m), 7,47-of 7.60 (3H, m), of 7.69 (1H, dt, J = 7,5, and 1.6 Hz), of 7.75 (1H, t, J = 1.6 Hz), 7,83-7,89 (2H, m)to 8.12 (1H, d, J = 8,3 Hz), 9,07 (1H, d, J = 1.9 Hz), 10,28 (1H, s).

Example 197

of 0.21 ml cyclopentene, 0.14 g of potassium acetate, of 0.13 g of tetrabutylammonium chloride, 3.1 mg of triphenylphosphine and 2.7 mg of palladium acetate are added to a solution containing 0.20 g of tert-butyl 2-(benzamido)-4-iodobenzoate in 1.0 ml of N,N-dimethylformamide, at room temperature, and the mixture is stirred in nitrogen atmosphere at the same temperature for 17 hours. To the reaction mixture of 0.21 ml cyclopentene, 23 mg of potassium acetate, 3.1 mg of triphenylphosphine and 2.7 mg of palladium acetate, and the mixture was stirred at 70°C for 3 hours of stirring at room temperature for 9 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel[eluent: toluene], while receiving 94 mg of tert-butyl 2-(benzamido)-4-(2-cyclopenten-1-yl)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 1.62 (9H, s), 1,72-of 1.84 (1H, m), 2,37-2,61 (3H, m), 3,94-a 4.03 (1H, m), 5,78-of 5.82 (1H, m), 5,98-6,03 (1H, m), 6,93 (1H, DD, J = 8,3, 1,6 Hz), 7,49-to 7.59 (3H, m), 7,94 (1H, d, J = 8,3 Hz), 8,04-of 8.09 (2H, m), 8,80 (1H, d, J = 1.6 Hz), 12,22 (1H, s).

Example 198

A solution containing 87 mg of tert-butyl 2-(benzamido)-4-(2-cyclopenten-1-yl)benzoate in 10 ml triperoxonane acid, stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure, the obtained residue is added methanol, and the solid is separated by filtration, to thereby obtain 52 mg of 2-(benzamido)-4-(2-cyclopenten-1-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,62-of 1.74 (1H, m), 2,35-to 2.55 (3H, m), 3,92-4,00 (1H, m), 5,78-of 5.83 (1H, m), 6,00-6,04 (1H, m), 7,03 (1H, DD, J = 8,2, 1.5 Hz), EUR 7.57-to 7.68 (3H, m), 7,93 shed 8.01 (3H, m), 8,63 (1H, d, J = 1.5 Hz), 12,24 (1H, s).

Example 199

5.0 mg of 5% palladium on coal are added to a solution containing 25 mg of 2-(benzamido)-4-(2-cyclopenten-1-yl)benzoic acid in a mixture of 1.0 ml of methanol and 0.5 ml of ethyl acetate, and the mixture is stirred at room temperature in a hydrogen atmosphere for 7 hours and then at 40°C for 8 hours and stirred at 45°C for 15 hours. Insoluble matter is removed by filtration, and dissolve Italy is evaporated under reduced pressure. To the obtained residue is added methanol and the solid is separated by filtration, while receiving 16 mg of 2-(benzamido)-4-cyclopentylmethyl acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,52 is 1.86 (6H, m), 1,98-2,12 (2H, m), 3,02-of 3.12 (1H, m), 7,10 (1H, DD, J = 8.0 a, 1,6 Hz), EUR 7.57-to 7.68 (3H, m), 7,94-of 8.00 (3H, m), to 8.70 (1H, d, J = 1.6 Hz), 12,22 (1H, s).

Example 200

0.11 g of 4-nitrophenylarsonic acid, 0.11 g of sodium bicarbonate, 1.2 ml of ethanol, 0.6 ml of water and 31 mg of tetrakis(triphenylphosphine)palladium(0) are added to a solution containing 0.20 g of tert-butyl 2-(benzamido)-4-bromobenzoate 4.0 ml of toluene, and the resulting mixture is refluxed under nitrogen atmosphere for 3 hours. After cooling the reaction mixture to room temperature, add saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 10:1], while receiving 40 mg of tert-butyl 2-(benzamido)-4-(4-nitrophenyl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: 1.57 in (9H, s), 7,60-of 7.70 (4H, m), 7,98-of 8.04 (3H, m), of 8.09 (1H, d, J = 8,8 Hz), 35-8,40 (3H, m), of 8.90 (1H, d, J = 1.7 Hz), 11,66 (1H, s).

Examples 201-205

Compounds shown in table 25, receive the same manner as in example 200.

Table 25

tert-Butyl 2-(benzamido)-4-(4-chlorophenyl)benzoate

1H-NMR (DMSO-d6) δ: 1.57 in (9H, s), 7,55 (1H, DD, J = 8,4, and 1.6 Hz), 7,58-of 7.70 (5H, m), 7,73 for 7.78 (2H, m), 7,97-8,02 (2H, m), of 8.04 (1H, d, J = 8,4 Hz), cent to 8.85 (1H, d, J = 1.6 Hz), of 11.69 (1H, s).

tert-Butyl 2-(benzamido)-4-(3,5-dichlorophenyl)benzoate

1H-NMR (DMSO-d6) δ: of 1.56 (9H, s), 7,60-of 7.70 (4H, m), 7,72-7,73 (1H, m), to 7.77 (2H, d, J = 1.7 Hz), 7,98-of 8.04 (3H, m), 8,77 (1H, d, J = 2.0 Hz), 11,58 (1H, s).

tert-Butyl 2-(benzamido)-4-(3,5-dimethyl-4-hydroxyphenyl)benzoate

1H-NMR (CDCl3) δ: 1,65 (9H, s), of 2.33 (6H, s), 4,78 (1H, s), 7,29 (1H, DD, J = 8,4, 1.8 Hz), was 7.36 (2H, s), 7,51-of 7.60 (3H, m), 8,03 (1H, d, J = 8,4 Hz), 8,06-8,11 (2H, m), 9,18 (1H, d, J = 1,8 Hz), to 12.28 (1H, s).

tert-Butyl 2-(benzamido)-4-(2-oxindol-5-yl)benzoate

1H-NMR (CDCl3) δ: 1,65 (9H, s)to 3.64 (2H, s), of 6.96 (1H, d, J = 8.1 Hz), 7,29 (1H, DD, J = 8,5, 1.9 Hz), 7,52-the 7.65 (5H, m), 7,82 (1H, s), 8,05-8,11 (3H, m), which 9.22 (1H, d, J = 1.9 Hz), 12,30 (1H, s).

tert-Butyl 2-(benzamido)-4-(3-chloro-2-forfinal)benzoate

1H-NMR (DMSO-d6) δ: 1.57 in (9H, s), 7,40 (1H, t, J = 7.9 Hz), 7,43-7,47 (1H, m), 7,54-7,72 (5H, m), of 7.96 shed 8.01 (2H, m), 8,07 (1H, d, J = 8,3 Hz), 8,72 (1H, s), 11,66 (1H, s).

Example 206

0.10 g of 2,6-diftorhinolonom acid, 0.52 g of cesium carbonate, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl sequentially add the keys to the solution, containing 0.20 g of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.5 ml of toluene, at room temperature, and the mixture is stirred under nitrogen atmosphere at 80°C for 1 hour and 10 minutes and then refluxed for 1 hour. After cooling the reaction mixture to room temperature, add 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, and the resulting mixture is refluxed under nitrogen atmosphere for 1 hour. After cooling the reaction mixture to room temperature, add 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl and the resulting mixture is refluxed under nitrogen atmosphere for 1 hour. After cooling the reaction mixture to room temperature, add 2.0 ml of toluene, 0.04 g of 2,6-diftorhinolonom acid, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl and the resulting mixture is refluxed under nitrogen atmosphere for 1 hour. After cooling the reaction mixture to room temperature, add saturated aqueous solution of sodium bicarbonate and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with a saturated aqueous solution of sodium bicarbonate and saturated aqueous rest the rum sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 20:1], while receiving 31 mg of tert-butyl 2-(benzamido)-4-(2,6-differenl)benzoate as a white solid.

1H-NMR (DMSO-d6) δ: 1.57 in (9H, s), 7,26 and 7.36 (3H, m), 7,53-to 7.67 (4H, m), 7,95-of 8.00 (2H, m), 8,07 (1H, d, J = 8.0 Hz), 8,57-8,61 (1H, m), 11,63 (1H, s).

Example 207

48 mg of 5-bromination, 40 mg of sodium bicarbonate, 0.6 ml of ethanol, 0.3 ml of water and 11 mg of tetrakis(triphenylphosphine)palladium(0) are added to a solution containing 80 mg of tert-butyl 2-(benzamido)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate in 1.6 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 5 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and water. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 20:1], while receiving 47 mg of tert-butyl 2-(benzamido)-4-(benzothiophen-5-yl)be the of Tata in the form of a white solid.

1H-NMR (CDCl3) δ: of 1.66 (9H, s), 7,40-7,44 (2H, m)to 7.50 (1H, d, J = 5.4 Hz), 7,51-to 7.61 (3H, m), 7,71 (1H, DD, J = 8,5) and 1.7 Hz), of 7.96 (1H, d, J = 8,3 Hz), 8,08-8,13 (3H, m), 8,19 (1H, d, J = 1.5 Hz), 9,34 (1H, d, J = 1.7 Hz), 12,31 (1H, s).

Examples 208-210

Compounds shown in table 26, receive the same manner as in example 207.

Table 26

tert-Butyl 2-(benzamido)-4-(benzofuran-5-yl)benzoate

1H-NMR (CDCl3) δ: of 1.66 (9H, s), at 6.84 (1H, DD, J = 2,2, 1.0 Hz), 7,38 (1H, DD, J = 8,3, 2.0 Hz), 7,51-to 7.61 (4H, m), of 7.64-to 7.68 (2H, m), of 7.96 (1H, d, J = 1.5 Hz), 8.07-a to 8.12 (3H, m), of 9.30 (1H, d, J = 2.0 Hz), 12,29 (1H, s).

tert-Butyl 2-(benzamido)-4-(1H-indol-4-yl)benzoate

1H-NMR (CDCl3) δ: of 1.66 (9H, s), 6,93-6,97 (1H, m), 7,24 and 7.36 (3H, m), 7,40-to 7.50 (2H, m), 7,50-of 7.60 (3H, m), 8.07-a 8,13 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 8,31 (1H, s), was 9.33 (1H, d, J = 1.5 Hz), 12,24 (1H, s).

tert-Butyl 2-(benzamido)-4-(4-(1H-pyrrol-1-yl)phenyl)benzoate

1H-NMR (CDCl3) δ: of 1.66 (9H, s)6,38 (2H, t, J = 2.2 Hz), 7,16 (2H, t, J = 2.2 Hz), 7,35 (1H, DD, J = 8,3) and 1.7 Hz), 7,47-7,52 (2H, m), 7,52-to 7.61 (3H, m), 7,76-of 7.82 (2H, m), 8.07-a to 8.12 (3H, m), 9,29 (1H, d, J = 1.7 Hz), 12,29 (1H, C).

Example 211

A solution containing 40 mg of tert-butyl 2-(benzamido)-4-(4-nitrophenyl)benzoate in 3.0 ml triperoxonane acid, stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added ethyl acetate and methanol, and the solid is separated by filtration, while receiving 15 mg of 2-(benzo is Mido)-4-(4-nitrophenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,60-of 7.70 (4H, m), 7,98-8,04 (4H, m), to 8.20 (1H, d, J = 8.6 Hz), 8,39 (2H, d, J = 8.5 Hz), 9,16 (1H, s), of 12.26-12,32 (1H, usher.).

Examples 212-221

Compounds shown in table 27, get in the same way as in example 211.

Table 27

2-(Benzamido)-4-(4-chlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,53 (1H, DD, J = 8,3, 1.8 Hz), to 7.59-of 7.70 (5H, m), 7,75-7,79 (2H, m), 7,97 shed 8.01 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), the remaining 9.08 (1H, d, J = 1,8 Hz), to 12.28 (1H, s).

2-(Benzamido)-4-(3,5-dichlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,58-of 7.70 (4H, m), 7,73 (1H, t, J = 1,8 Hz), to 7.77 (2H, d, J = 2.0 Hz), 7,97-8,02 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,03 (1H, d, J = 1.7 Hz), 12,24-12,31 (1H, usher.).

2-(Benzamido)-4-(3,5-dimethyl-4-hydroxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 2.26 (6H, s), 7,32 (2H, s), 7,44 (1H, DD, J = 8,3, 1.8 Hz), 7,58-of 7.70 (3H, m), of 7.96-8,02 (2H, m), 8,07 (1H, d, J = 8,3 Hz), at 8.60 (1H, s), 9,01 (1H, d, J = 1,8 Hz), 12,27 (1H, s), 13,60-13,80 (1H, usher.).

2-(Benzamido)-4-(2-oxindol-5-yl)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.60 (2H, s), 6,97 (1H, d, J = 8.1 Hz), 7,47 (1H, DD, J = 8,5, 1.8 Hz), 7,56-of 7.70 (5H, m), of 7.96-8,02 (2H, m), 8,10 (1H, d, J = 8.5 Hz), 9,06 (1H, d, J = 1,8 Hz), 10,57 (1H, s)to 12.28 (1H, s), 13,60-13,90 (1H, user.).

2-(Benzamido)-4-(3-chloro-2-forfinal)benzoic acid

1H-NMR (DMSO-d6) δ: 7,37-7,44 (2H, m), 7,56-7,72 (5H, m), 7,95-of 8.00 (2H, m), 8,17 (1H, d, J = 8,3 Hz), 8,97 (1H, s), 12,22 of 12.26 (1H, usher.).

2-(Benzamido)-4-(2,6-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: 7.24 to 7,35 3H, m), 7,52-of 7.69 (4H, m), 7,93-of 8.00 (2H, m), 8,17 (1H, d, J = 8,3 Hz), 8,86 (1H, s), 12,24 (1H, s).

2-(Benzamido)-4-(benzothiophen-5-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,58-7,71 (5H, m), 7,74 (1H, DD, J = 8,5) and 1.7 Hz), 7,87 (1H, d, J = 5.4 Hz), 7,98-of 8.04 (2H, m), 8,14-to 8.20 (2H, m), of 8.27 (1H, d, J = 1.4 Hz), 9,18 (1H, d, J = 1.7 Hz), 12,31 (1H, s), of 13.75-13,95 (1H, usher.).

2-(Benzamido)-4-(benzofuran-5-yl)benzoic acid

1H-NMR (DMSO-d6) δ: to 7.09 (1H, DD, J = 2,2, 1.0 Hz), 7,56 (1H, DD, J = 8,3, 2.0 Hz), to 7.59-7,71 (4H, m), 7,76 (1H, d, J = 8.5 Hz), 7,98-of 8.04 (2H, m), 8,03 (1H, d, J = 1.5 Hz), of 8.09 (1H, d, J = 2.2 Hz), 8,15 (1H, d, J = 8,3 Hz), 9,14 (1H, d, J = 2.0 Hz), 12,30 (1H, s), 13,70-13,95 (1H, usher.).

2-(Benzamido)-4-(1H-indol-4-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 6.75 in-6,79 (1H, m), 7,21-7,27 (2H, m), 7,47-rate of 7.54 (2H, m), 7,53 (1H, DD, J = 8,3, 1.8 Hz), 7,58-of 7.70 (3H, m), 7,98-8,03 (2H, m), 8,17 (1H, d, J = 8,3 Hz), 9,17 (1H, d, J = 1,8 Hz), 11,37 (1H, s), 12,29 (1H, s).

2-(Benzamido)-4-(4-(1H-pyrrol-1-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,32 (2H, t, J = 2.2 Hz), of 7.48 (2H, t, J = 2.2 Hz), EUR 7.57 (1H, DD, J = 8,4, 1.9 Hz), to 7.59-7,71 (3H, m), 7,74-7,80 (2H, m), 7,80-7,86 (2H, m), 7,98-8,03 (2H, m), 8,15 (1H, d, J = 8,4 Hz), 9,12 (1H, d, J = 1.9 Hz), 12,30 (1H, s).

Example 222

44 mg of 3-Chlorfenvinphos acid, 49 mg of sodium carbonate and 6 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 90°C for 15 hours. After cooling, the reaction is Oh mixture to room temperature, add to 5.7 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) and the mixture was stirred at 110°C for 9 hours and 30 minutes. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(benzamido)-4-(3-chlorophenyl)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(3-chlorophenyl)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added methanol, and the solid is separated by filtration, thus obtaining 21 mg of 2-(benzamido)-4-(3-chlorophenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,52-7,74 (7H, m), to 7.77 (1H, s), 7,97-8,03 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,06 (1H, d, J = 2.0 Hz), 12,27 (1H, s).

Examples 223-231

Compounds shown in table 28, receive the same manner as in example 222.

Table 28

2-(Benzamido)-4-(3-ftoh the Nile)benzoic acid

1H-NMR (DMSO-d6) δ: 7,27 and 7.36 (1H, m), 7,53-of 7.70 (7H, m), of 7.96-8,02 (2H, m)to 8.14 (1H, d, J = 8.0 Hz), the remaining 9.08 (1H, d, J = 1.7 Hz), 12,24 (1H, s).

2-(Benzamido)-4-(2,3-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,34-7,47 (3H, m), 7,50-of 7.70 (4H, m), 7.95 is shed 8.01 (2H, m), 8,17 (1H, d, J = 8,3 Hz), 8,98 (1H, s), 12,25 (1H, s).

2-(Benzamido)-4-(3,5-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: of 7.36 (1H, TT, J = 9,1, 2.2 Hz), 7,43-7,51 (2H, m), 7,56-7,71 (4H, m), of 7.96-8,03 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,04 (1H, d, J = 1.7 Hz), 12,27 (1H, s).

2-(Benzamido)-4-(2-hydroxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6.90 to-7,02 (2H, m), 7,20-7,28 (1H, m), 7,32 (1H, DD, J = 7,7, 1,6 Hz), 7,40 (1H, DD, J = 8,3) and 1.7 Hz), EUR 7.57-of 7.69 (3H, m), 7.95 is shed 8.01 (2H, m), 8,07 (1H, d, J = 8,3 Hz), 8,96 (1H, d, J = 1.7 Hz), of 9.75 (1H, s), 12,20-12,45 (1H, usher.).

2-(Benzamido)-4-(4-isopropoxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: is 1.31 (6H, d, J = 6,1 Hz), 4,65 was 4.76 (1H, m), 7,05-7,10 (2H, m), of 7.48 (1H, DD, J = 8,3) and 1.7 Hz), to 7.59-of 7.70 (5H, m), of 7.96-8,02 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 9,05 (1H, d, J = 1.7 Hz), 12,32 (1H, s).

2-(Benzamido)-4-(2-phenoxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,91-6,97 (2H, m), 7,02-to 7.09 (2H, m), 7.29 trend is 7.50 (5H, m), 7,54-of 7.69 (4H, m), 7,93-of 8.00 (2H, m), of 8.04 (1H, d, J = 8,2 Hz), 8,99 (1H, d, J = 1.6 Hz), 12,22 (1H, s).

2-(Benzamido)-4-(4-(triptoreline)phenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,51-EUR 7.57 (3H, m), 7,58-of 7.70 (3H, m), 7,84-7,89 (2H, m), of 7.96-8,02 (2H, m), 8,15 (1H, d, J = 8,3 Hz), the remaining 9.08 (1H, d, J = 1.7 Hz), 12,27 (1H, s), 13,70-14,05 (1H, usher.).

2-(Benzamido)-4-(2,3-dimetilfenil)benzoic acid

1NMR (DMSO-d 6) δ: 2,16 (3H, s), of 2.33 (3H, s), to 7.09 (1H, d, J = 7,1 Hz), to 7.15 (1H, DD, J = 8,1) and 1.7 Hz), 7,17-7,27 (2H, m), EUR 7.57-of 7.69 (3H, m), 7,94-to 7.99 (2H, m), 8,11 (1H, d, J = 8.1 Hz), to 8.70 (1H, d, J = 1.7 Hz), 12,30 (1H, s).

2-(Benzamido)-4-(3-nitrophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: to 7.59-7,71 (4H, m), 7,82-7,88 (1H, m), 7,98-8,03 (2H, m), 8,19 (1H, d, J = 8,3 Hz), 8,21 (1H, DDD, J = 7,8, and 1.7, 1.0 Hz), 8,29-to 8.34 (1H, m), 8,48-and 8.50 (1H, m), 9,14 (1H, d, J = 1.9 Hz), 12,27 (1H, s), 13,80-14,15 (1H user.).

Example 232

42 mg of 3-gidroksietilirovannogo acid, 49 mg of sodium carbonate and 6 ml deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 90°C for 15 hours. After cooling the reaction mixture to room temperature, add 6 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) and the mixture was stirred at 110°C for 9 hours and 30 minutes. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The floor is obtained residue purified column chromatography on silica gel [Flash Tube 2008, manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(benzamido)-4-(3-(hydroxymethyl)phenyl)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(3-(hydroxymethyl)phenyl)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], while receiving 12 mg of 2-(benzamido)-4-(3-(hydroxymethyl)phenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: br4.61 (2H, s), 5,26-of 5.40 (1H, usher.), 7,41 (1H, d, J = 7,6 Hz), 7,47-of 7.55 (2H, m), 7,58-7,73 (5H, m), 7,97-of 8.04 (2H, m), 8,15 (1H, d, J = 8,3 Hz), which is 9.09 (1H, d, J = 1.7 Hz), of 12.33 (1H, s).

Examples 233-235

Compounds shown in table 29, receive the same manner as in example 232.

Table 29

2-(Benzamido)-4-(2-isopropoxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 1.26 in (6H, d, J = 6,1 Hz), 4,59-4,72 (1H, m), 7,05 (1H, t, J = 7,3 Hz), 7,17 (1H, d, J = 8.1 Hz), 7,32-7,41 (3H, m), EUR 7.57-to 7.68 (3H, m), 7.95 is shed 8.01 (2H, m), 8,07 (1H, d, J = 8,3 Hz), 8,98 (1H, d, J = 1.7 Hz).

2-(Benzamido)-4-(3-(triptoreline)phenyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 7.48 (1H, d, J = 8.0 Hz), EUR 7.57 (1H, DD, J = 8,3, 1.9 Hz), to 7.59-7,73 (5H, m), 7,79 (1H, d, J = 7.8 Hz), 7,97-8,03 (2H, m), 8,16 (1H, d, J = ,3 Hz), the remaining 9.08 (1H, d, J = 1.9 Hz), 12,35 (1H, s).

2-(Benzamido)-4-(3-were)benzoic acid

1H-NMR (DMSO-d6) δ: 2,42 (3H, s), 7,28 (1H, d, J = 7,6 Hz), the 7.43 (1H, t, J = 7,6 Hz), 7,49-EUR 7.57 (3H, m), to 7.59-of 7.70 (3H, m), 7,97-8,02 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 9,07 (1H, d, J = 1.7 Hz), 12,29 (1H, s).

Example 236

60 mg of 4-phenoxyphenylacetic acid, 49 mg of sodium carbonate and 6 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, add 6 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1]while this is tert-butyl-2-(benzamido)-4-(4-phenoxyphenyl)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(4-phenoxyphenyl)benzoate add 5.0 ml triperoxonane acid, and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane: ethyl acetate = 1:2], while receiving 8.0 mg 2-(benzamido)-4-(4-phenoxyphenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,08-of 7.23 (5H, m), 7,41-of 7.48 (2H, m), 7,51 (1H, DD, J = 8,3, 1.9 Hz), 7,58-of 7.70 (3H, m), 7,74-7,79 (2H, m), of 7.96-8,02 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 9,07 (1H, d, J = 1.9 Hz), 12,30 (1H, s).

Example 237

The following connection receive the same manner as in example 236.

2-(Benzamido)-4-(4-benzoylphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: EUR 7.57 to 7.75 (7H, m), 7,78-to 7.84 (2H, m), 7,89-of 7.96 (4H, m), 7,98-8,03 (2H, m), 8,19 (1H, d, J = 8,3 Hz), 9,17 (1H, d, J = 1.5 Hz), 12,29 (1H, s).

Example 238

46 mg of 4-(dimethylamino)phenylboronic acid, 49 mg of sodium carbonate and 5.7 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room rate is atory add to 5.7 mg deposited on the polymer di(acetato)dicyclohexylphenylphosphine(II) and the mixture was stirred at 110°C for 24 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(benzamido)-4-(4-(dimethylamino)phenyl)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(4-(dimethylamino)phenyl)benzoate add 5.0 ml triperoxonane acid, and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure, add ethyl acetate and water, and the pH is adjusted to 6.5 with a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added methanol, and the solid is separated by filtration, thus obtaining 3.8 mg 2-(benzamido)-4-(4-(dimethylamino)phenyl)benzoic acid as a pale relegating substances.

1H-NMR (DMSO-d6) δ: 2,98 (6H, s), 6,83-6,89 (2H, m), 7,45 (1H, DD, J = 8,3 ,1.8 Hz), 7,58-of 7.69 (5H, m), 7,97-8,02 (2H, m), of 8.06 (1H, d, J = 8,3 Hz), 9,05 (1H, d, J = 1,8 Hz), 12,32 (1H, s).

Example 239

38 mg of 2-methylphenylacetic acid, 49 mg of sodium carbonate and 6 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 110°C for 20 hours. After cooling the reaction mixture to room temperature, add 6 mg deposited on the polymer bis(acetato)triphenylphosphine(II) and the mixture was stirred at 110°C for 22 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(benzamido)-4-(2-were)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(2-were)benzo is that add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure, the obtained residue is added methanol and the solid is separated by filtration, while receiving 14 mg of 2-(benzamido)-4-(2-were)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: to 2.29 (3H, s), 7.18 in-7,38 (5H, m), EUR 7.57-of 7.69 (3H, m), 7,94-of 8.00 (2H, m)to 8.12 (1H, d, J = 8.1 Hz), a total of 8.74 (1H, d, J = 1.4 Hz), 12,27 (1H, s).

Examples 240-242

Compounds shown in table 30, receive the same manner as in example 239.

Table 30

2-(Benzamido)-4-(4-were)benzoic acid

1H-NMR (DMSO-d6) δ: of 2.38 (3H, s), 7,35 (2H, d, J = 8.0 Hz), to 7.50 (1H, DD, J = 8,3, 1.9 Hz), 7,58-of 7.70 (5H, m), of 7.96-8,02 (2H, m)to 8.12 (1H, d, J = 8,3 Hz), 9,07 (1H, d, J = 1.9 Hz), of 12.33 (1H, s).

2-(Benzamido)-4-(3-cyanophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,58-of 7.70 (4H, m), 7,76 (1H, t, J = 7.8 Hz), 7,92-of 7.97 (1H, m), 7,97-8,02 (2H, m), 8,05-8,11 (1H, ), 8,16 (1H, d, J = 8,3 Hz), 8,19-8,23 (1H, m), the remaining 9.08 (1H, d, J = 2.0 Hz), to 12.28 (1H, s).

2-(Benzamido)-4-(4-cyanophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,56-of 7.69 (4H, m), of 7.90-8,02 (6H, m), 8,16 (1H, d, J = 8,3 Hz), 9,10 (1H, d, J = 2.0 Hz), 12,29 (1H, s).

Example 243

39 mg of 4-hydroxyphenylarsonic acid, 49 mg of sodium carbonate and 6 mg deposited on the polymer bis(acetato)triphenylphosphine(II) are added to a solution containing 70 mg of Tr is t-butyl-2-(benzamido)-4-bromobenzoate in 2.5 ml N,N-dimethylacetamide, and the mixture was stirred at 110°C for 20 hours. After cooling the reaction mixture to room temperature, add 6 mg deposited on the polymer bis(acetato)triphenylphosphine(II) and the mixture was stirred at 110°C for 22 hours. After cooling the reaction mixture to room temperature, the insoluble matter is removed by filtration and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 2:1], while receiving tert-butyl-2-(benzamido)-4-(4-hydroxyphenyl)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(4-hydroxyphenyl)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 55-90% acetonitrile/0.1% of triperoxonane acid], while receiving 1.9 mg 2-(benzamido)-4-(4-hydroxyphenyl)benzoic acid as a white solid which CSOs substances.

1H-NMR (DMSO-d6) δ: 6,88-of 6.96 (2H, m), 7,44 (1H, DD, J = 8,3, 1.9 Hz), 7,56-of 7.69 (5H, m), of 7.96-8,02 (2H, m), 8,08 (1H, d, J = 8,3 Hz), 9,03 (1H, d, J = 1.9 Hz), 9,79 (1H, s), of 12.33 (1H, s).

Example 244

The following connection receive the same manner as in example 243.

2-(Benzamido)-4-(3-hydroxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 6,86 (1H, DD, J = 8,1, 1.9 Hz), 7,11-7,19 (2H, m), 7,33 (1H, t, J = 7.9 Hz), 7,47 (1H, DD, J = 8,1) and 1.7 Hz), to 7.59-of 7.70 (3H, m), 7,97-8,02 (2H, m), 8,13 (1H, d, J = 8.1 Hz), 9,06 (1H, d, J = 1.7 Hz), RS 9.69 (1H, s), 12,30 (1H, s).

Example 245

56 mg of 2-ftorhinolonovy acid, 0.10 g of sodium bicarbonate, 0.6 ml of ethanol, 0.3 ml of water and 23 mg of tetrakis(triphenylphosphine)palladium(0) are added to a solution containing 0.15 g of tert-butyl 2-(benzamido)-4-bromobenzoate 2.1 ml of toluene and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add 17 mg of 2-ftorhinolonovy acid and 23 mg of tetrakis(triphenylphosphine)palladium(0) and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add toluene and a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and dissolve Italy is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 10:1], while receiving tert-butyl-2-(benzamido)-4-(2-forfinal)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(2-forfinal)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, and add toluene. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 93 mg of 2-(benzamido)-4-(2-forfinal)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,34-7,44 (3H, m), 7,47-of 7.55 (1H, m), 7,56-of 7.70 (4H, m), 7,94 shed 8.01 (2H, m), 8,16 (1H, d, J = 8,3 Hz), 8,96-9,00 (1H, m), 12,27 (1H, s).

Examples 246-250

Compounds shown in table 31, receive the same manner as in example 245.

Table 31

2-(Benzamido)-4-(3-fluoro-4-were)benzoic acid

1H-NMR (DMSO-d6) δ: 2,28-of 2.34 (3H, m), 7,42-EUR 7.57 (4H, m), 7,58-of 7.70 (3H, m), of 7.96-8,02 (2H, m)to 8.12 (1H, d, J = 8,3 Hz), 9,06 (1H, d, J = 1.7 Hz), 12,27 (1H, s).

2-(Benzamido)-4-(2-chlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,29 (1H, DD, J = 8,3) and 1.7 Hz), 7,45-7,51 (3H, m), EUR 7.57-of 7.69 (4H, m), 7,94-of 8.00 (2H, m), 8,15 (1H, d, J = 8,3 Hz), 8,84 (1H, d, J = 1.7 Hz), to 12.28 (1H, s).

2-(Benzamido)4-(3,4-dichlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: EUR 7.57 (1H, DD, J = 8,3, 1.9 Hz), 7,58-of 7.70 (3H, m), 7,73 (1H, DD, J = 8,3, 2.2 Hz), 7,81 (1H, d, J = 8.6 Hz), of 7.96 shed 8.01 (3H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,05 (1H, d, J = 1.9 Hz), 12,24 (1H, s).

2-(Benzamido)-4-(5-chloro-2-forfinal)benzoic acid

1H-NMR (DMSO-d6) δ: 7,40 is 7.50 (2H, m), 7,55-of 7.70 (5H, m), 7.95 is shed 8.01 (2H, m), 8,16 (1H, d, J = 8.0 Hz), 8,96 (1H, s), 12,27 (1H, s).

2-(Benzamido)-4-(2,6-dimetilfenil)benzoic acid

1H-NMR (DMSO-d6) δ: 2,03 (6H, s), 7,02 (1H, DD, J = 8,1, 1,6 Hz), 7,13-of 7.25 (3H, m), 7,56-of 7.69 (3H, m), 7,93-to 7.99 (2H, m), 8,15 (1H, d, J = 8.1 Hz), 8,53 (1H, d, J = 1.6 Hz), 12,29 (1H, s).

Example 251

83 mg of 2-chloro-6-ftorhinolonovy acid, 0.10 g of sodium bicarbonate, 0.6 ml of ethanol, 0.3 ml of water and 23 mg of tetrakis(triphenylphosphine)palladium(0) are added to a solution containing 0.15 g of tert-butyl 2-(benzamido)-4-bromobenzoate 2.1 ml of toluene, and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add 21 mg of 2-chloro-6-ftorhinolonovy acid and 23 mg of tetrakis(triphenylphosphine)palladium(0) and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add toluene and a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with saturated aqueous Rast is the PR of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 10:1], while receiving tert-butyl-2-(benzamido)-4-(2-chloro-6-forfinal)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(2-chloro-6-forfinal)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, and add toluene. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 70-100% acetonitrile/0.1% of triperoxonane acid], while receiving 5,8 mg of 2-(benzamido)-4-(2-chloro-6-forfinal)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7.23 percent (1H, DD, J = 8,3, 1,6 Hz), 7,37 was 7.45 (1H, m), 7,49-of 7.70 (5H, m), 7,93-to 7.99 (2H, m), 8,17 (1H, d, J = 8,3 Hz), 8,73-8,77 (1H, m), to 12.28 (1H, s).

Example 252

0.15 g of 4-bromo-2-chlorophenol, 0.18 g of sodium bicarbonate, 0.6 ml of ethanol, 0.3 ml of water and 42 mg of tetrakis(triphenylphosphine)palladium(0) are added at room temperature to a solution containing of 0.37 g of tert-butyl 2-(benzamido)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate in 2.1 ml of toluene, and the resulting mixture is boiled with reverse holodilny the MD within 4 hours. After cooling the reaction mixture to room temperature, add toluene and a saturated aqueous solution of sodium bicarbonate. The organic layer is separated, and add ethyl acetate, washed with saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane, and the solid is separated by filtration, thus obtaining tert-butyl-2-(benzamido)-4-(3-chloro-4-hydroxyphenyl)benzoate.

To the obtained tert-butyl 2-(benzamido)-4-(3-chloro-4-hydroxyphenyl)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, and add toluene. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 94 mg of 2-(benzamido)-4-(3-chloro-4-hydroxyphenyl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,13 (1H, d, J = 8,3 Hz), of 7.48 (1H, DD, J = 8,3) and 1.7 Hz), 7,56 (1H, DD, J = 8,4, and 2.3 Hz), EUR 7.57-7,72 (4H, m), of 7.96 shed 8.01 (2H, m), of 8.09 (1H, d, J = 8,3 Hz), 9,01 (1H, d, J = 1.7 Hz), 10,50-10,66 (1H, usher.), of 12.26 (1H, s).

Example 253

0,031 ml indoline, 0.12 g of cesium carbonate, 1.7 mg of Tris(dibenzylideneacetone)diplegia(0), 0.8 mg of ACE the ATA palladium and 4.4 mg of 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl added to the solution, containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate 1.4 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 3 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 10:1], while receiving 77 mg of tert-butyl 2-(benzamido)-4-(indolin-1-yl)benzoate as a yellow oil.

1H-NMR (CDCl3) δ: 1,63 (9H, s), 3,17 (2H, t, J = 8,4 Hz), 4,10 (2H, t, J = 8,4 Hz)6,86 (1H, TD, J = 7,4, 0.8 Hz), of 6.96 (1H, DD, J = 8,9 and 2.5 Hz), 7,16-7,24 (2H, m), 7,46-EUR 7.57 (4H, m), of 7.97 (1H, d, J = 8,9 Hz), 8,06-8,10 (2H, m), 8,81 (1H, d, J = 2.5 Hz), 12,40 (1H, s).

Example 254

A solution containing 75 mg of tert-butyl 2-(benzamido)-4-(indolin-1-yl)benzoate in 5.0 ml triperoxonane acid, stirred at room temperature for 1 hour and 30 minutes. The solvent is evaporated under reduced pressure, add ethyl acetate and water and the pH is adjusted to 6.5 with a saturated aqueous rastvorosmesitelnuju sodium. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with water and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added methanol, and the solid is separated by filtration, to thereby obtain 51 mg of 2-(benzamido)-4-(indolin-1-yl)benzoic acid as a yellow solid.

1H-NMR (DMSO-d6) δ: 3,17 (2H, t, J = 8,4 Hz)4,06 (2H, t, J = 8,4 Hz), to 6.88 (1H, t, J = 7.4 Hz), to 6.95 (1H, DD, J = 9,0, 2.4 Hz), 7,19 (1H, t, J = 7,6 Hz), 7,27 (1H, d, J = 7,3 Hz), of 7.48 (1H, d, J = 8.0 Hz), 7,58-of 7.69 (3H, m), of 7.96-8,02 (2H, m), 8,02 (1H, d, J = 9.0 Hz), 8,82 (1H, d, J = 2.4 Hz), 12,50 (1H, s), 13,26 (1H, s).

Examples 255-277

Compounds shown in table 32, receive the same manner as in example 34.

Table 32

4-Phenethyl-2-(2-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,13 (1H, DD, J = 8,1) and 1.7 Hz), 7,16-7,22 (1H, m), 7,26-to 7.32 (4H, m), 7,73-7,81 (1H, m), 7,81-7,86 (2H, m), 7,86-of 7.97 (2H, m), 8,49 (1H, s), are 11.62 (1H, s), 13,50-13,70 (1H, usher.).

4-Phenethyl-2-(2-phenylacetamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,82-to 2.94 (4H, m in), 3.75 (2H, s), of 6.99 (1H, DD, J = 8,2, 1.5 Hz), 7,13-7,20 (1H, m), 7,20-to 7.32 (5H, m), 7,32-7,42 (4H, m), to 7.84 (1H, d, J = 8,2 Hz), 8,44 (1H, d, J = 1.5 Hz), 11,16 (1H, s).

2-(2-Methylbenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: of 2.45 (3H, s), 2,90-to 3.02 (4H, m), to 7.09 (1H, DD, J = 8,3,1,6 Hz), 7,16-of 7.23 (1H, m), 7,26-7,37 (6H, m), 7,40-7,50 (1H, m), to 7.59 (1H, d, J = 7,6 Hz), 7,94 (1H, d, J = 8,3 Hz), to 8.62 (1H, s), are 11.62 (1H, s), 13,45-13,65 (1H, usher.).

2-(3-Methylbenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,42 (3H, s), 2,90-to 3.02 (4H, m), was 7.08 (1H, DD, J = 8,1, 1,6 Hz), 7,16-7,22 (1H, m), 7,25-to 7.32 (4H, m), 7,44-7,52 (2H, m), 7,73-7,81 (2H, m), of 7.96 (1H, d, J = 8.1 Hz), 8,67 (1H, d, J = 1.6 Hz), 12,24 (1H, s).

2-(4-Methylbenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,40 (3H, s), 2,88-a 3.01 (4H, m), 7,07 (1H, DD, J = 8,1) and 1.7 Hz), 7,15-7,22 (1H, m), 7.24 to to 7.32 (4H, m), 7,40 (2H, d, J = 8,2 Hz), 7,86 (2H, d, J = 8,2 Hz), 7,95 (1H, d, J = 8.1 Hz), 8,67 (1H, d, J = 1.7 Hz), 12,22 (1H, s).

2-(4-Nitrobenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,89 totaling 3.04 (4H, m), 7,09-7,14 (1H, m), 7,15-7,22 (1H, m), 7,25-to 7.32 (4H, m), of 7.97 (1H, d, J = 8,3 Hz), 8,19 (2H, d, J = 8,8 Hz), 8,44 (2H, d, J = 8,8 Hz), 8,58 (1H, d, J = 1.5 Hz).

2-(3,4-Dimethylbenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,32 (3H, s), 2,32 (3H, s), 2,90-of 3.00 (4H, m), 7,06 (1H, d, J = 8,2 Hz), 7,15-7,20 (1H, m), 7,25-7,30 (4H, m), 7,35 (1H, d, J = 7,7 Hz), to 7.68 (1H, d, J = 7,7 Hz), 7,74 (1H, s), 7,95 (1H, d, J = 8,2 Hz), 8,68 (1H, s), 12,16-12,20 (1H, usher.).

2-(2,3-Dimethylbenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,30 (6H, s), 2,90-of 3.00 (4H, m), 7,06-7,11 (1H, m), 7,16-7,38 (8H, m), to 7.93 (1H, d, J = 8.0 Hz), 8,61 (1H, s), 11,50-to 11.56 (1H, usher.).

2-(3-Nitrobenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90 was 3.05 (4H, m), 7,10-7,21 (2H, m), 7,26-7,30 (4H, m), 7,89-to 7.99 (2H, m), at 8.36-8,42 (1H, m), of 8.47-charged 8.52 (1H, m), 8,58 (1H, d, J = 1.7 Hz), 8,76 (1H, t, J = 2.0 Hz), 12,36-12,48 (1H, in the Il.).

4-Phenethyl-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,11 (1H, d, J = 8.0 Hz), 7,16-7,21 (1H, m), 7,25-7,31 (4H, m), 7,94-8,02 (3H, m), 8,15 (2H, d, J = 7,6 Hz), 8,61 (1H, s)to 12.28 (1H, s).

2-(Benzothiophen-2-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,10 (1H, DD, J = 8,1, 1.2 Hz), 7,17-7,21 (1H, m), 7,25-to 7.32 (4H, m), of 7.48-of 7.55 (2H, m), 7,98 (1H, d, J = 8.1 Hz), 8,06-8,11 (3H, m), 8,53-to 8.57 (1H, m), 12,34 (1H, s).

2-(2-Perbenzoic)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,91-of 3.00 (4H, m), 7,10 (1H, d, J = 8.0 Hz), 7,16-7,21 (1H, m), 7,25-7,31 (4H, m), 7,38-7,44 (2H, m), of 7.64-of 7.69 (1H, m), of 7.90-of 7.96 (2H, m), 8,66 (1H, s), 11,94-12,00 (1H, usher.), 13,54-13,60 (1H, usher.).

2-(3-Perbenzoic)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-of 3.00 (4H, m), 7,10 (1H, DD, J = 8,1) and 1.7 Hz), 7,16-7,20 (1H, m), 7,25-7,31 (4H, m), 7,49-7,52 (1H, m), of 7.64-7,73 (2H, m), 7,78-7,81 (1H, m), of 7.96 (1H, d, J = 8.1 Hz), 8,60-to 8.62 (1H, m), 12,16-12,22 (1H, user.), 13,64-13,76 (1H, usher.).

2-(2,6-Differentaite)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,12-7,21 (2H, m), 7,26-7,33 (6H, m), to 7.61-of 7.69 (1H, m), 7,94 (1H, d, J = 8.0 Hz), and 8.50 (1H, s), 11,74-11,82 (1H, usher.).

4-Phenethyl-2-(3-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,90-3,03 (4H, m), 7,10-7,13 (1H, m), 7,16-7,21 (1H, m), 7,25-7,31 (4H, m), 7,87 (1H, t, J = 7.9 Hz), of 7.96 (1H, d, J = 8.1 Hz), of 8.04 (1H, d, J = 7.8 Hz), 8,24-of 8.28 (2H, m), at 8.60 (1H, s)to 12.28-12,34 (1H, user.).

2-(2-Chlorobenzamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,12 (1H, is d, J = 8,3, 1.5 Hz), 7,16-7,22 (1H, m), 7,26-to 7.32 (4H, m), of 7.48-7,63 (3H, m), 7,71 (1H, DD, J = 7,3, 1.7 Hz), 7,94 (1H, d, J = 8,3 Hz), 8,53-8,59 (1H, m), are 11.62-11,70 (1H, usher.), 13,54-13,62 (1H, usher.).

2-(3-Chlorobenzamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,10 (1H, DD, J = 8,3, 1.2 Hz), 7,16-7,22 (1H, m), 7,25-7,31 (4H, m), of 7.64 (1H, t, J = 7.8 Hz), 7,72 to 7.75 (1H, m), to $ 7.91 (1H, d, J = 7.8 Hz), 7.95 is-of 7.97 (2H, m), 8,58-8,61 (1H, m), 12,18-12,24 (1H user.).

2-(4-Chlorobenzamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-a 3.01 (4H, m), to 7.09 (1H, DD, J = 8.0 a, 1.0 Hz), 7,16-7,20 (1H, m), 7,26-to 7.32 (4H, m), of 7.69 (2H, d, J = 8.5 Hz), 7,93-7,98 (3H, m), 8,61-8,63 (1H, m), 12,17-12,22 (1H, usher.).

2-(2,4-Bis(trifluoromethyl)benzamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,14-7,22 (2H, m), 7,26-7,30 (4H, m), to 7.93 (1H, d, J = 8.0 Hz), of 8.09 (1H, d, J = 8.0 Hz), 8,24 (1H, s), of 8.28 (1H, d, J = 8,3 Hz), at 8.36-8,39 (1H, m), 11,60-11,64 (1H, usher.).

2-(2,4-Dichlorobenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 7,10-to 7.15 (1H, m), 7,16-7,22 (1H, m), 7,26-to 7.32 (4H, m), to 7.61 (1H, DD, J = 8,4, and 2.1 Hz), of 7.75 (1H, d, J = 8,3 Hz), 7,81 (1H, d, J = 2.1 Hz), to 7.93 (1H, d, J = 8,3 Hz)and 8.50 (1H, s), are 11.62-11,68 (1H, usher.).

Triptorelin 4-phenethyl-2-((E)-3-(pyridin-4-yl)acrylamide)benzoic acid

1H-NMR (DMSO-d6) δ: 2,88-of 3.00 (4H, m), to 7.09 (1H, DD, J = 8,1, 1.5 Hz), 7,16-7,21 (1H, m), 7.23 percent-7,29 (4H, m), 7,32 (1H, d, J = 15.6 Hz), to 7.67 (1H, d, J = 15.6 Hz), to 7.93 (1H, d, J = 8.1 Hz), 8,00 (2H, d, J = 6.2 Hz), 8,53 (1H, d, J = 1.5 Hz), 8,78 (2H, d, J = 6.2 Hz), of $ 11.48 (1H, s).

4-Phenethyl-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1 H-NMR (DMSO-d6) δ: 2.91 in-3,03 (4H, m), to 6.39 (2H, t, J = 2.2 Hz), 7,13 (1H, DD, J = 8,1, 1,6 Hz), 7,16-7,31 (5H, m), 7,58 (2H, t, J = 2.2 Hz), of 7.97 (1H, d, J = 8.1 Hz), 8,44 (1H, t, J = 2.3 Hz), to 8.57 (1H, d, J = 1.6 Hz), 8,96 (1H, d, J = 2.3 Hz), 9,16 (1H, d, J = 2.3 Hz), 12,20 (1H, s).

4-Phenethyl-2-(2-(pyrrolidin-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 1,80-1,89 (4H, m), 2,88-a 3.01 (4H, m), 3,32-of 3.42 (4H, m), 6,72 (1H, DD, J = 7,4, 4,8 Hz), was 7.08 (1H, DD, J = 8,2) and 1.7 Hz), 7,15-7,22 (1H, m), 7.24 to 7,31 (4H, m), 7,78 (1H, DD, J = 7,4, 1.9 Hz), 7,92 (1H, d, J = 8,2 Hz), by 8.22 (1H, DD, J = 4,8, 1.9 Hz), to 8.57 (1H, s), 11,58 (1H, s).

Example 278

2.0 mg of 5% palladium on coal are added to a solution containing 7.0 mg of 2-(4-nitrobenzamide)-4-venetiancasino acid in a mixture of 1.0 ml of methanol and 2.0 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 2 hours. After removing insoluble substances by filtration, the solvent is evaporated under reduced pressure, thus obtaining 4.0 mg of 2-(4-aminobenzamide)-4-venetiancasino acid as a yellow solid.

1H-NMR (DMSO-d6) δ: 2,80-2,96 (4H, m), 5,55-5,91 (2H, usher.), of 6.61 (2H, d, J = 8.6 Hz), for 6.81 (1H, DD, J = 8.0 a, 1,6 Hz), 7,15-7,20 (1H, m), 7.24 to 7,31 (4H, m), 7,74 (2H, d, J = 8.6 Hz), 7,89 (1H, d, J = 8.0 Hz), 8,61 (1H, d, J = 1.6 Hz).

Example 279

0,061 ml of pyridine and 0,086 ml of 2,6-dichlorobenzonitrile added sequentially to a solution containing 0.15 g of tert-butyl 2-amino-4-penicillinate 3.0 is l of toluene, at room temperature, and the resulting mixture is refluxed for 8 hours. The reaction mixture is cooled to room temperature, and add saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2,6-dichlorobenzamide)-4-venetianskt.

To the obtained tert-butyl 2-(2,6-dichlorobenzamide)-4-penicillinate add 3.0 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, while receiving 18 mg of 2-(2,6-dichlorobenzamide)-4-venetiancasino acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,91-to 3.02 (4H, m), 7,15-7,22 (2H, m), 7,26-7,30 (4H, m), 7,53-EUR 7.57 (1H, m), to 7.61-to 7.64 (2H, m), of 7.64 (1H, d, J = 1.7 Hz), 7,94 (1H, d, J = 8.0 Hz), 8,48-and 8.50 (1H, usher.), to 11.56-are 11.62 (1H, usher.).

Example 280

0,090 ml of pyridine and 0.12 ml of 2,6-dichlorobenzoyl is Yes added sequentially to the solution, containing 0.15 g of tert-butyl 2-amino-4-phenylbenzoate in 3.0 ml of toluene, at room temperature, and the resulting mixture is refluxed for 4 hours. The reaction mixture is cooled to room temperature, and successively add 0,023 ml of pyridine and 0,040 ml of 2,6-dichlorobenzonitrile, and the resulting mixture is refluxed for 2 hours. The reaction mixture is cooled to room temperature and add water. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2,6-dichlorobenzamide)-4-phenylbenzoate.

To the obtained tert-butyl 2-(2,6-dichlorobenzamide)-4-phenylbenzoate add 3.0 ml triperoxonane acid and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining 0.10 g of 2-(2,6-dichlorobenzamide)-4-phenylbenzene acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,46-the 7.65 (7H, m), 7,73 (2H, d, J = 7,8 Hz)and 8.1 (1H, d, J = 8,3 Hz), 8,87-8,89 (1H, usher.), are 11.62-11,68 (1H, usher.), 13,76-13,88 (1H, usher.).

Example 281

0,084 ml of pyridine and 0.11 ml of 2,6-dichlorobenzonitrile added sequentially to a solution containing 0.15 g of tert-butyl 2-amino-4-phenoxybenzoate in 3.0 ml of toluene, at room temperature, and the resulting mixture is refluxed for 4 hours. The reaction mixture is cooled to room temperature and successively added 0,021 ml of pyridine and 0.037 ml 2,6-dichlorobenzonitrile, and the resulting mixture is refluxed for 4 hours. The reaction mixture is cooled to room temperature and add water. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2,6-dichlorobenzamide)-4-phenoxybenzoate.

To the obtained tert-butyl 2-(2,6-dichlorobenzamide)-4-phenoxybenzoate add 3.0 ml triperoxonane acid, and the mixture is stirred at room temperature for 1 hour. The solvent is evaporated under reduced pressure, and to receive the resultant residue is added diisopropyl ether, and the solid is separated by filtration, while receiving 70 mg of 2-(2,6-dichlorobenzamide)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,9, and 2.1 Hz), 7,19-of 7.23 (2H, m), 7,26-to 7.32 (1H, m), of 7.48-EUR 7.57 (3H, m), to 7.61-the 7.65 (2H, m), with 8.05 (1H, d, J = 8,9 Hz), 8,24-of 8.28 (1H, m).

Example 282

0,063 ml of triethylamine and 0,040 ml of 2-tormentilla added sequentially to a solution containing 60 mg of tert-butyl 2-amino-4-phenylbenzoate in 3.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture are added 0.51 g aminomethylpropanol polystyrene, and the mixture is stirred at room temperature over night. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2-perbenzoic)-4-phenylbenzoate.

To the obtained tert-butyl 2-(2-perbenzoic)-4-phenylbenzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is dobavlaut diisopropyl ether, and the solid is separated by filtration, to thereby obtain 61 mg of 2-(2-perbenzoic)-4-phenylbenzene acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,39 is 7.50 (3H, m), 7,52-to 7.59 (3H, m), 7,65-7,76 (3H, m), of 7.96 (1H, TD, J = 7,8, 1.8 Hz), 8,13 (1H, d, J = 8,3 Hz), 9,07 (1H, d, J = 1.7 Hz), 12,00-12,10 (1H, usher.), 13,65-13,85 (1H, usher.).

Examples 283-319

Compounds shown in table 33, receive the same manner as in example 282.

Table 33

2-(3-Perbenzoic)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,44-7,49 (1H, m), 7,51-7,58 (4H, m), 7,65-7,72 (1H, m), 7,72-to 7.77 (3H, m), 7,81-a 7.85 (1H, m)to 8.14 (1H, d, J = 8,3 Hz), of 9.02 (1H, d, J = 1.7 Hz), 12,25 (1H, s).

2-(4-Perbenzoic)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,43-to 7.59 (6H, m), 7,71-to 7.77 (2H, m), 8,02-of 8.09 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,04 (1H, d, J = 1.7 Hz), 12,24 (1H, s), of 13.75-13,95 (1H, usher.).

2-(2,4-Differentaite)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: to 7.32 (1H, TD, J = 8,4, 2.4 Hz), 7,44-7,58 (5H, m), 7,70-7,76 (2H, m), of 8.04 (1H, TD, J = 8,8, and 6.6 Hz), 8,13 (1H, d, J = 8,3 Hz), 9,04 (1H, d, J = 2.0 Hz), 12,02-12,06 (1H, m), 13,77 (1H, s).

2-(2,6-Differentaite)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,28-to 7.35 (2H, m), 7,44 is 7.50 (1H, m), 7,52-to 7.61 (3H, m), 7,62 for 7.78 (3H, m)to 8.12 (1H, d, J = 8,3 Hz), of 8.90 (1H, s), up 11,86 (1H, s), 13,70-13,95 (1H, usher.).

2-(2-Methylbenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,48 (3H, s), 7,33-7,39 (2H, m), 7,43-to 7.50 (2H, m), 7,50-to 7.59 (3H, m), 7,62-7,66 (1H, m), 7,71-7,76 (2H, m), 8,11 (1H, d, J = 8,3 Hz), 9,03 (1H, d, J = 1.7 Hz), of 11.69 (1H, s), 13,71 (1H, s).

2-(3-Methylbenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,43 (3H, s), 7,44-7,58 (6H, m), 7,71-7,83 (4H, m)to 8.14 (1H, d, J = 8.0 Hz), which is 9.09 (1H, d, J = 1.7 Hz), 12,27 (1H, s), 13,80-13,95 (1H, usher.).

2-(4-Methylbenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,41 (3H, s), 7,40-7,58 (6H, m), 7,72 to 7.75 (2H, m), 7,89 (2H, d, J = 8,3 Hz)to 8.14 (1H, d, J = 8,3 Hz), which is 9.09 (1H, d, J = 1.7 Hz), 12,24 (1H, s), of 13.75-13,90 (1H, usher.).

4-Phenyl-2-(2-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,47 (1H, TT, J = 7,4, 1.5 Hz), 7,52-of 7.60 (3H, m), 7,70-7,94 (6H, m)to 8.12 (1H, d, J = 8,3 Hz), 8,88 (1H, s), of 11.69 (1H, s), 13,65-13,85 (1H, usher.).

4-Phenyl-2-(3-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,47 (1H, TT, J = 7,3, 1.5 Hz), 7,52-7,58 (3H, m), 7,72-to 7.77 (2H, m), 7,86-to $ 7.91 (1H, m), with 8.05 (1H, d, J = 8.1 Hz), 8,14 (1H, d, J = 8,3 Hz), 8,27-8,32 (2H, m), 9,01 (1H, d, J = 2.0 Hz), 12,38 (1H, s), 13,80-14,05 (1H, usher.).

4-Phenyl-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,47 (1H, TT, J = 7,6, 1.5 Hz), 7,52-to 7.59 (3H, m), 7,72-to 7.77 (2H, m), 8,01 (2H, d, J = 8,3 Hz), 8,12 were 8.22 (3H, m), of 9.02 (1H, d, J = 1.7 Hz), 12,34 (1H, s).

2-(3,4-Dimethylbenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,32 (3H, s), of 2.33 (3H, s), 7,37 (1H, d, J = 7.8 Hz), 7,44-7,58 (4H, m), 7,69-7,79 (4H, m), 8,13 (1H, d, J = 8,3 Hz), which is 9.09 (1H, d, J = 2.0 Hz), 12,25 (1H, s), of 13.75-13,95 (1H, usher.).

2-(2,3-Dimethylbenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), of 2.33 (3H, s), from 7.24 (1H, t, J = 7,6 Hz), 7,34 (1H, d, J = ,6 Hz), 7,41 (1H, d, J = 7,6 Hz), 7,44-7,58 (4H, m), 7,71 to 7.75 (2H, m), 8,11 (1H, d, J = 8,3 Hz), 9,03 (1H, s), 11,60 (1H, s), 13,60-13,80 (1H, usher.).

2-(6-Morpholinopropan-3-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 3,60 of 3.75 (8H, m), 7,00 (1H, d, J = 9.0 Hz), 7,43-7,58 (4H, m), 7,70 to 7.75 (2H, m), of 8.04 (1H, DD, J = 9,0, 2,5 Hz)to 8.12 (1H, d, J = 8,3 Hz), the rate of 8.75 (1H, d, J = 2.5 Hz), 9,06 (1H, d, J = 1.7 Hz), 12,08 (1H, s), 13,70-13,90 (1H, usher.).

2-(Cyclohexanecarboxylate)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 1,14-of 1.52 (5H, m), 1.60-to 1,71 (1H, m), 1,72-of 1.81 (2H, m), 1,88 of 1.99 (2H, m), 2,30-2,39 (1H, m), 7,41-7,56 (4H, m), 7,65-7,71 (2H, m), of 8.06 (1H, d, J = 8,3 Hz), of 8.90 (1H, d, J = 1.7 Hz), to 11.28 (1H, s), 13,61 (1H with).

4-Phenyl-2-(2-phenylacetamido)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.80 (2H, s), 7,26-rate of 7.54 (9H, m), of 7.64-of 7.69 (2H, m), 8,03 (1H, d, J = 8,3 Hz), 8,87 (1H, d, J = 1.7 Hz), 11,23 (1H, s), 13,55-of 13.75 (1H, usher.).

2-(Cinnamamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 6,94 (1H, d, J = 15.6 Hz), 7,41-EUR 7.57 (7H, m), 7,66 (1H, d, J = 15.6 Hz), 7,69 for 7.78 (4H, m), 8,10 (1H, d, J = 8,3 Hz), 8,98 (1H, d, J = 1.7 Hz), 11,42 (1H, s), 13,55-of 13.75 (1H, usher.).

2-(2-Phenoxyacetamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: of 4.77 (2H, s), 7,03 (1H, t, J = 7,3 Hz), 7,09-to 7.15 (2H, m), 7,33-7,40 (2H, m), 7,43-EUR 7.57 (4H, m), to 7.67-7,73 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 9,06 (1H, d, J = 1.7 Hz), of 12.26 (1H, s)13,82 (1H, s).

2-(Furan-2-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 6,77 (1H, DD, J = 3,5, 1.7 Hz), 7,30 (1H, DD, J = 3,5, 0.6 Hz), 7,44-EUR 7.57 (4H, m), 7,69 to 7.75 (2H, m), 8,02 (1H, DD, J = 1,7, 0.6 Hz), 8,13 (1H, d, J = 8,3 Hz), 9,03 (1H, d, J = 2.0 Hz), of 12.26 (1H, s), 1379 (1H, C).

4-Phenyl-2-(thiophene-2-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,30 (1H, DD, J = 5.0 and 3.8 Hz), 7,44 is 7.50 (1H, m), 7,50-7,58 (3H, m), 7,70-7,76 (2H, m), 7,78 (1H, DD, J = 3,8, 1.1 Hz), of 7.96 (1H, DD, J = 5.0 and 1.1 Hz), 8,13 (1H, d, J = 8,3 Hz), to 8.94 (1H, d, J = 1.7 Hz), 12,23 (1H, C)13,80-14,00 (1H, usher.).

2-(Benzo[1,3]dioxol-5-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 6,17 (2H, s), 7,13 (1H, d, J = 8.1 Hz), 7,43-to 7.59 (6H, m), 7,70-7,76 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 9,05 (1H, d, J = 2.0 Hz), 12,14 (1H, s), 13,70-13,95 (1H, usher.).

2-(2,3-Dihydrobenzo[1,4]dioxin-6-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 4,28-4,39 (4H, m), 7,07 (1H, d, J = 8,3 Hz), 7,43-EUR 7.57 (6H, m), 7,70 to 7.75 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 9,07 (1H, d, J = 1.7 Hz), 12,16 (1H, s), 13,70-13,90 (1H, usher.).

2-(Benzothiophen-5-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,45-7,58 (4H, m), the 7.65 (1H, d, J = 5.4 Hz), 7,72 for 7.78 (2H, m), 7,92-of 7.97 (2H, m), 8,15 (1H, d, J = 8,3 Hz), of 8.25 (1H, d, J = 8.5 Hz), 8,53 (1H, d, J = 1.5 Hz), 9,11 (1H, d, J = 1.7 Hz), 12,37 (1H, s).

2-(1-Methyl-1H-benzotriazol-5-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 4,39 (3H, s), 7,45-7,51 (1H, m), 7,53-to 7.59 (3H, m), 7,73 for 7.78 (2H, m), 8,07 (1H, d, J = 8,8 Hz), 8,16 (2H, d, J = 8.1 Hz), 8,66 (1H, s), 9,07 (1H, d, J = 1.7 Hz), 12,37 (1H, s).

2-(3-Nitrobenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: of 7.48 (1H, TT, J = 7,3, 1.5 Hz), 7,52-to 7.61 (3H, m), 7,72 for 7.78 (2H, m), to 7.93 (1H, t, J = 8.0 Hz), 8,15 (1H, d, J = 8,3 Hz), to 8.41 (1H, DDD, J = 8.0 a, 1,5, 1.0 Hz), 8,51 (1H, DDD, J = 8,1, 2,4, 1.0 Hz), 8,78-8,80 (1H, m), 8,98-9,00 (1H, m), 12,42 (1H, s).

2-(B shall souran-5-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,16 (1H, DD, J = 2,2, 1.0 Hz), 7,47 (1H, TT, J = 7,4, 1.5 Hz), 7,50-to 7.59 (3H, m), 7,72 for 7.78 (2H, m), 7,83 (1H, d, J = 8.5 Hz), of 7.96 (1H, DD, J = 8,7, 1.7 Hz), 8,12-8,19 (2H, m), with 8.33 (1H, d, J = 1.7 Hz), 9,10 (1H, d, J = 1.7 Hz), 12,31 (1H, s).

2-(Benzothiazol-2-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,46-7,51 (1H, m), 7,53-7,79 (7H, m), 8,16 is 8.22 (2H, m), 8,29-8,32 (1H, m), 9,10 (1H, d, J = 1.7 Hz), 13,04 (1H, s).

2-(Benzothiophen-3-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,45-to 7.61 (6H, m), 7,73-7,80 (2H, m), 8,11-8,18 (2H, m), 8,51-8,55 (1H, m), 8,56 (1H, s), 9,04 (1H, d, J = 2.0 Hz), 12,09 (1H, s).

2-(Benzofuran-2-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,37-of 7.48 (1H, m), of 7.48 (1H, TT, J = 7,4, 1.5 Hz), 7,52-to 7.59 (4H, m), 7,69 for 7.78 (4H, m), 7,86 (1H, d, J = 7.8 Hz), 8,16 (1H, d, J = 8,3 Hz), the remaining 9.08 (1H, d, J = 1.7 Hz), was 12.61 (1H, s).

2-(Benzothiophen-2-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,45-to 7.59 (6H, m), 7,71 for 7.78 (2H, m), 8,06-8,18 (4H, m), of 8.95 (1H, d, J = 1.5 Hz), 12,43 (1H, s).

4-Phenyl-2-(1-phenyl-1H-pyrazole-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: to 7.09 (1H, d, J = 2.0 Hz), 7,41-of 7.55 (9H, m), of 7.64-of 7.69 (2H, m), 7,88 (1H, d, J = 2.0 Hz), to 8.12 (1H, d, J = 8,3 Hz), 8,77 (1H, d, J = 1.7 Hz), 12,12 (1H, s).

2-(2,2-Diphenylacetamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: of 5.34 (1H, s), 7,28 (1H, TT, J = 7,2, 1.7 Hz), 7,33-7,54 (13H, m), 7,65-7,71 (2H, m), 8,02 (1H, d, J = 8,3 Hz), of 8.92 (1H, d, J = 1.7 Hz), 11,42 (1H, s), 13,50-13,70 (1H, usher.).

2-(2-Chlorobenzamido)-4-phenylbenzene acid

1H-NMR (who MCO-d 6) δ: 7,44-the 7.65 (7H, m), 7,71 for 7.78 (3H, m)to 8.12 (1H, d, J = 8,3 Hz), 8,97 (1H, s), 11,72 (1H, s).

2-(3-Chlorobenzamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,44 is 7.50 (1H, m), 7,52-to 7.59 (3H, m), 7,66 (1H, t, J = 7.9 Hz), 7,71 for 7.78 (3H, m), 7,92-of 7.96 (1H, m), to 7.99 (1H, t, J = 1,8 Hz), 8,14 (1H, d, J = 8.0 Hz), of 9.00 (1H, d, J = 2.0 Hz), 12,27 (1H, s).

2-(4-Chlorobenzamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,47 (1H, TT, J = 7,4, and 1.6 Hz), 7,52-to 7.59 (3H, m), 7.68 per-to 7.77 (4H, m), 7,97-8,02 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,02-9,04 (1H, m), 12,25 (1H, s).

2-(2,4-Dichlorobenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,47 (1H, TT, J = 7,3, 1.5 Hz), 7,52-to 7.59 (3H, m), 7,63 (1H, DD, J = 8,3, 2.0 Hz), 7,70-7,76 (2H, m), 7,79 (1H, d, J = 8,3 Hz), 7,83 (1H, d, J = 2.0 Hz), 8,11 (1H, d, J = 8,3 Hz), 8,91 (1H, s), 11,72 (1H, s).

4-Phenyl-2-(2,4-bis(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,47 (1H, TT, J = 7,4, and 1.6 Hz), 7,53-EUR 7.57 (2H, m), 7,60 (1H, DD, J = 8,3) and 1.7 Hz), 7,70-7,76 (2H, m), 8,10-of 8.15 (2H, m), of 8.25 (1H, s), 8,28-of 8.33 (1H, m), 8,76 (1H, d, J = 1.4 Hz), of 11.69 (1H, s).

4-Phenyl-2-(3-phenylpropanamide)benzoic acid

1H-NMR (DMSO-d6) δ: was 2.76 (2H, t, J = 7,6 Hz), of 2.97 (2H, t, J = 7,6 Hz), 7,16-7,22 (1H, m), 7,26-7,31 (4H, m), 7,42-of 7.48 (2H, m), 7,50-7,56 (2H, m), 7,65-7,71 (2H, m), with 8.05 (1H, d, J = 8,3 Hz), cent to 8.85 (1H, d, J = 2.0 Hz), 11,23 (1H, C), 13,55-of 13.75 (1H, usher.).

Example 320

1.3 ml of methylene chloride and 1.3 μl of N,N-dimethylformamide and 0,031 ml oxalicacid add sequentially to 69 mg of 6-(piperidine-1-yl)pyridine-3-carboxylic acid at room temperature, and the mixture is stirred at the same temperature for 1 hour. The reaction mixture was added to a solution of 57 mg of tert-butyl 2-amino-4-phenoxybenzoate in a mixture of 3.7 ml of methylene chloride and 0.22 ml of triethylamine, and the mixture is stirred at room temperature for 2 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 8:1], while receiving tert-butyl-4-phenoxy-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoate.

To the obtained tert-butyl-4-phenoxy-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, and water is added, and regulate pH to 6.5 with a saturated aqueous solution of sodium bicarbonate. The solid is separated by filtration, to thereby obtain 23 mg of 4-phenoxy-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,47 is 1.70 (6H, m), 3,62-3,70 (4H, m), of 6.73 (1H, DD, J = 9,0, 2.6 Hz), 6,93 (1H, d, J = 9,2 Hz), 7,15-to 7.18 (2H, m), 7,25-7,30 (1H, m), 7,45-7,52 (2H, m), to $ 7.91 (1H, DD, J = 9,2, and 2.6 Hz), with 8.05 (1H, d, J = 9.0 Hz), scored 8.38 (1H, d, J = 2.6 Hz), 8,63 (1H, d, J = 2.6 Hz), 12,22 (1H, s).

Example 321

0,059 ml of triethylamine and 0.037 ml 2-tormentilla added sequentially to a solution containing 60 mg of tert-butyl 2-amino-4-phenoxybenzoate in 3.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture of 0.48 g aminomethylpropanol polystyrene, and the mixture is stirred at room temperature over night. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2-perbenzoic)-4-phenoxybenzoate.

To the obtained tert-butyl 2-(2-perbenzoic)-4-phenoxybenzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, while receiving 30 mg of 2-(2-perbenzoic)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,9 and 2.5 Hz), 7,16-7,21 (2H, m), 7,25-7,31 (1H, m), 7,35-7,53 (4H, m), 7,63-of 7.69 (1H, m), 7,88 (1H, TD, J = 7,8, 1.8 Hz), of 8.06 (1H, d, J = 8,9 Hz), to 8.41(1H, d, J = 2.5 Hz), 12,15-12,19 (1H, usher.), 13,50-13,70 (1H, usher.).

Examples 322-344

Compounds shown in table 34, receive the same manner as in example 321.

Table 34

4 Phenoxy-2-(2-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,77 (1H, DD, J = 8,8, 2.4 Hz), 7,19 (2H, d, J = 7.8 Hz), 7,28 (1H, t, J = 7.4 Hz), 7,46-7,53 (2H, m), 7,74-7,87 (3H, m), 7,89 (1H, d, J = 8.1 Hz), of 8.04 (1H, d, J = 8,8 Hz), of 8.27 (1H, d, J = 2.4 Hz), 11,82 (1H, ), 13,60 (1H, s).

4 Phenoxy-2-(4-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,9 and 2.5 Hz), 7,16-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,47-7,53 (2H, m), 7,98 (2H, d, J = 8,3 Hz), 8,06-to 8.14 (3H, m), of 8.37 (1H, d, J = 2.5 Hz), 12,51 (1H, s), 13,65-13,85 (1H, usher.).

2-(2-Methylbenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,42 (3H, s), of 6.75 (1H, DD, J = 8,9, 2.7 Hz), 7,16-7,21 (2H, m), 7,25 was 7.36 (3H, m), 7,41-7,52 (3H, m), 7,56-of 7.60 (1H, m), with 8.05 (1H, d, J = 8,9 Hz), 8,39 (1H, d, J = 2.7 Hz), 11,82 (1H, s), 13,45-13,65 (1H, user.).

2-(3-Methylbenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,40 (3H, s), 6,77 (1H, DD, J = 8,8, 2.7 Hz), 7,16-7,21 (2H, m), 7,26-7,31 (1H, m), 7,44-7,53 (4H, m), 7.68 per-7,74 (1H, m), 7,74 (1H, s), 8,07 (1H, d, J = 8,8 Hz), to 8.41 (1H, d, J = 2.7 Hz), 12,41 (1H, s), 13,71 (1H, s).

2-(4-Methylbenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,39 (3H, s)6,76 (1H, DD, J = 8,9, and 2.6 Hz), 7,15-7,21 (2H, m), 7,26-7,31 (1H, m), 7,39 (2H, d, J = 8,2 Hz), 7,46-7,52 (2H, m), 7,82 (2H, d, J = 8,2 Hz), 8,07 (1H, d, J = 8,9 Hz), to 8.41 (1H, d, J = 2.6 Hz), 12,38 (1H, s), 13,67 (1, C).

2-(4-Nitrobenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: PC 6.82 (1H, DD, J = 8,9 and 2.5 Hz), 7,16-7,21 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,53 (2H, m), of 8.09 (1H, d, J = 8,9 Hz), 8,12-8,17 (2H, m), 8,35 (1H, d, J = 2.5 Hz), 8,40-to 8.45 (2H, m), of 12.53 (1H, s), 13,65-13,90 (1H, user.).

2-(3,4-Dimethylbenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,30 (6H, s), of 6.75 (1H, DD, J = 8,9, 2.7 Hz), 7,15-7,20 (2H, m), 7,25-7,31 (1H, m), 7,34 (1H, d, J = 7.8 Hz), 7,45-7,53 (2H, m), of 7.64 (1H, DD, J = 7,8, 1.9 Hz), 7,71 (1H, d, J = 1.9 Hz), of 8.06 (1H, d, J = 8,9 Hz), 8,42 (1H, d, J = 2.7 Hz), 12,38 (1H, s), 13,69 (1H, s).

2-(2,3-Dimethylbenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: of 2.27 (3H, s)to 2.29 (3H, s), of 6.75 (1H, DD, J = 8,8, and 2.6 Hz), 7,16-7,38 (6H, m), 7,46-7,52 (2H, m), of 8.04 (1H, d, J = 8,8 Hz), 8,40 (1H, d, J = 2.6 Hz), 11,73 (1H, s), 13,53 (1H, s).

2-(6-Morpholinopropan-3-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 3,57 of 3.75 (8H, m), of 6.75 (1H, DD, J = 9,0, 2.6 Hz), of 6.96 (1H, d, J = 9.0 Hz), 7,13-7,22 (2H, m), 7.24 to 7,31 (1H, m), 7,45-7,53 (2H, m), of 7.97 (1H, DD, J = 9,0, 2.4 Hz), with 8.05 (1H, d, J = 9.0 Hz), of 8.37 (1H, d, J = 2,6 Hz), 8,67 (1H, d, J = 2.4 Hz), 12,23 (1H, s), 13,64 (1H, s).

4 Phenoxy-2-(2-phenylacetamido)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.73 (2H, s), 6,69 (1H, DD, J = 8,8, 2,5 Hz), 7,12 (2H, d, J = 7,6 Hz), 7,22-7,38 (6H, m), 7,43-7,49 (2H, m), of 7.96 (1H, d, J = 8,8 Hz), 8,21 (1H, d, J = 2.5 Hz), 11,35 (1H, s), 13,45 (1H, s).

2-(3-Perbenzoic)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,8, 2.7 Hz), 7,16-7,21 (2H, m), 7,26-7,31 (1H, m), 7,46-of 7.55 (3H, m), 7,62-of 7.70 (2H, m), 7,74 for 7.78 (1H, m), 8,08 (1H, d, J = 8,8 Hz), 8,35 (1H, d, J = 27 Hz), 12,42 (1H, s), 13,60-13,85 (1H, usher.).

2-(2,6-Differentaite)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.4 Hz), 7,19 (2H, d, J = 7.8 Hz), 7.24 to 7,34 (3H, m), 7,46-rate of 7.54 (2H, m), to 7.61-of 7.70 (1H, m), with 8.05 (1H, d, J = 8,8 Hz), 8,25-8,29 (1H, m), 11,99 (1H, s), 13,50-13,80 (1H, usher.).

4 Phenoxy-2-(3-(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.4 Hz), 7,16-7,21 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,53 (2H, m), a 7.85 (1H, t, J = 8.0 Hz), 8,03 (1H, d, J = 7.8 Hz), 8,08 (1H, d, J = 8,8 Hz), 8,18-8,24 (2H, m), 8,35 (1H, d, J = 2.4 Hz), 12,54 (1H, s).

2-(3-Nitrobenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.4 Hz), 7,17-7,21 (2H, m), 7,26-7,33 (1H, m), 7,46-rate of 7.54 (2H, m), 7,89 (1H, t, J = 7.9 Hz), 8,08 (1H, d, J = 8,8 Hz), 8,30-of 8.37 (2H, m), 8,46-and 8.50 (1H, m), 8,71 (1H, s), br12.62 (1H, s), 13,70-14,00 (1H, usher.).

2-(2-Chlorobenzamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,9, and 2.4 Hz), 7,16-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,63 (5H, m), of 7.69 (1H, DD, J = 7,4, and 1.6 Hz), with 8.05 (1H, d, J = 8,9 Hz), 8,30-to 8.34 (1H, m), up 11,86 (1H, s), 13,50-of 13.75 (1H, usher.).

2-(3-Chlorobenzamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,8, 2.4 Hz), 7,16-7,21 (2H, m), 7,25-7,31 (1H, m), 7,45-7,53 (2H, m), 7,60-the 7.65 (1H, m), 7,69-7,76 (1H, m), 7,84-of 7.95 (2H, m), 8,07 (1H, d, J = 8,8 Hz), a 8.34 (1H, d, J = 2.4 Hz), 12,43 (1H, ).

2-(4-Chlorobenzamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,9, and 2.6 Hz), 7,16-7,21 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,52 (2H, m), of 7.64-of 7.70 (2H, m), 7,88-of 7.95 (2H, m), 8,07 (1H, d, J = 8,9 Hz), at 8.36 (1H, d, J = 2.6 Hz), 12,42 (1H, s).

2-(2,4-Dichl is benzamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,8, 2.7 Hz), 7,18 (2H, d, J = 7.8 Hz), 7,28 (1H, t, J = 7.4 Hz), 7,45-7,53 (2H, m), 7,60 (1H, DD, J = 8,3, 2.2 Hz), 7,74 (1H, d, J = 8,3 Hz), 7,81 (1H, d, J = 1.9 Hz), with 8.05 (1H, d, J = 8,8 Hz), compared to 8.26-of 8.28 (1H, m), 11,88 (1H, s), 13,45-13,80 (1H, usher.).

2-(Benzothiophen-5-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,8, 2.7 Hz), 7,17-7,22 (2H, m), 7,27-to 7.32 (1H, m), 7,47-7,53 (2H, m), a 7.62 (1H, d, J = 5.4 Hz), 7,87 (1H, DD, J = 8,4, 1.7 Hz), to 7.93 (1H, d, J = 5.4 Hz), of 8.09 (1H, d, J = 8,8 Hz), by 8.22 (1H, d, J = 8,4 Hz), 8,44 (1H, d, J = 2.7 Hz), of 8.47 (1H, d, J = 1.7 Hz), to 12.52 (1H, s).

2-(Benzothiophen-2-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,8, and 2.6 Hz), 7,17-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,56 (4H, m), 8,04-to 8.12 (4H, m), of 8.28 (1H, d, J = 2.6 Hz), 12,57 (1H, s), 13,65-13,90 (1H, usher.).

4 phenoxy-2-(1-phenyl-1H-pyrazole-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: was 6.73 (1H, DD, J = 8,9, 2.7 Hz),? 7.04 baby mortality (1H, d, J = 2.1 Hz), 7,10-to 7.15 (2H, m), 7,20-of 7.25 (1H, m), 7,40-of 7.48 (7H, m), 7,86 (1H, d, J = 2.1 Hz), of 8.04 (1H, d, J = 8,9 Hz), 8,13 (1H, d, J = 2.7 Hz), 12,22 (1H, s).

4 Phenoxy-2-(2,4-bis(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,9, and 2.3 Hz), 7,19 (2H, d, J = 7.8 Hz), 7,26-7,31 (1H, m), 7,45-7,53 (2H, m), with 8.05 (1H, d, J = 8,9 Hz), of 8.09 (1H, d, J = 7.9 Hz), 8,19 (1H, d, J = 2.3 Hz), 8,23 (1H, s), of 8.27 (1H, d, J = 7.9 Hz), up 11,86 (1H, s).

4 Phenoxy-2-(3-phenylpropanamide)benzoic acid

1H-NMR (DMSO-d6) δ: 2,69 (2H, t, J = 7,7 Hz), 2,90 (2H, t, J = 7,7 Hz), 6,69 (1H, DD, J = 8,9 and 2.5 Hz), 7,11-7,21 (3H, m), 7,21-7,31 (5H, m), 7,43-to 7.50 (2H, m), 7,98 (1H, d, J = 8,9 is C), 8,21 (1H, d, J = 2.5 Hz), 11,36 (1H, s), 13,40-13,60 (1H, usher.).

Example 345

1.3 ml of methylene chloride and 1.3 μl of N,N-dimethylformamide and 0,031 ml oxalicacid successively added to 69 mg of 3,4-dimethoxyphenol acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution of 54 mg of tert-butyl 2-amino-4-phenylbenzoate in a mixture of 3.7 ml of methylene chloride and 0.22 ml of triethylamine, and the mixture is stirred at room temperature for 2 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], thus obtaining (E)-tert-butyl-2-(3-(3,4-acid)acrylamide)-4-phenylbenzoate.

To the obtained (E)-tert-butyl-2-(3-(3,4-acid)acrylamide)-4-phenylbenzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining 20 mg of (E)-2-(3-(3,4-acid)acrylamide)-4-vinylbenzoic acid in the form of the aircraft the CSO solids.

1H-NMR (DMSO-d6) δ: 3,81 (3H, s), 3,85 (3H, s), at 6.84 (1H, d, J = 15,5 Hz), 7,01 (1H, d, J = 8,3 Hz), 7,26 (1H, DD, J = 8,4, 1.7 Hz), 7,40 (1H, d, J = 1.5 Hz), 7,43-EUR 7.57 (4H, m), to 7.59 (1H, d, J = 15,5 Hz), 7,71 (2H, d, J = 7.8 Hz), of 8.09 (1H, d, J = 8,4 Hz), of 9.00 (1H, d, J = 1.7 Hz), 11,37 (1H, s), 13,50-of 13.75 (1H, usher.).

Examples 346-367

Compounds shown in table 35, receive the same manner as in example 345.

Table 35

Triptorelin 4-phenyl-2-((E)-3-(pyridin-4-yl)acrylamide)benzoic acid

1H-NMR (DMSO-d6) δ: 7,40 (1H, d, J = 15.6 Hz), 7,47 (1H, TT, J = 7,3, 1.5 Hz), 7,51-7,58 (3H, m), 7.68 per to 7.75 (3H, m), 8,07 (2H, d, J = 6,1 Hz), 8,11 (1H, d, J = 8,3 Hz), 8,82 (2H, d, J = 6,1 Hz), 8,96 (1H, d, J = 1.7 Hz), to 11.56 (1H, ).

2-(3-Methylpyridin-2-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,71 (3H, s), 7,44-to 7.61 (5H, m), 7,72-to 7.77 (2H, m), a 7.85-7,88 (1H, m)to 8.12 (1H, d, J = 8.0 Hz), 8,56-8,59 (1H, m), 9,20 (1H, d, J = 1.7 Hz), to 13.09 (1H, s), 13,45-13,70 (1H, usher.).

4-Phenyl-2-(3-phenylpropionamide)benzoic acid

1H-NMR (DMSO-d6) δ: 6,56-6,70 (1H, m), 7,21 (1H, d, J = 7.8 Hz), 7,27-to 7.32 (2H, m), 7,34-7,41 (3H, m), to 7.61-of 7.70 (3H, m), 7,88-a 7.92 (2H, m), 8,42 (1H, d, J = 7,8 Hz).

4-Phenyl-2-(6-phenylpyrimidine-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,45 is 7.50 (1H, m), 7,54-7,66 (6H, m), 7,74-7,79 (2H, m), 8,17 (1H, d, J = 8,3 Hz), 8,30 is 8.38 (2H, m), 8,67 (1H, d, J = 1.2 Hz), 9,24 (1H, d, J = 1.7 Hz), 9,49 (1H, d, J = 1.2 Hz), 13,24 (1H, s).

4-Phenyl-2-(5-phenyl-1H-pyrazole-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,38-of 7.55 (8H, m), to 7.67 to 7.75 (4H, m), 808 (1H, d, J = 8,3 Hz), of 8.95 (1H, d, J = 1.4 Hz), 11,65-RS 11.80 (1H, usher.), 12,82-12,90 (1H, usher.).

4-Phenyl-2-(3-phenyl-1H-pyrazole-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,25 (1H, s), 7,38-to 7.59 (7H, m), 7,71-to 7.77 (2H, m), 7,83-7,89 (2H, m), 8,13 (1H, d, J = 8.0 Hz), 9,17 (1H, s), 12,45 (1H, s), 14,01 (1H, s).

4-Phenyl-2-(3-phenylisoxazol-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,45-7,51 (1H, m), 7,53-7,63 (7H, m), 7,74 (2H, d, J = 7.8 Hz), 7,98-with 8.05 (2H, m), 8,16 (1H, d, J = 8,3 Hz), 9,05 (1H, d, J = 1.7 Hz), 12,56 (1H, s), of 13.75-14,10 (1H, usher.).

2-(3-Acetoxybenzoic)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: of 2.33 (3H, s), 7,43-to 7.50 (2H, m), 7,51-to 7.59 (3H, m), to 7.67 (1H, t, J = 7.9 Hz), 7,70-to 7.77 (3H, m), a 7.85-of 7.90 (1H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,03 (1H, d, J = 1.7 Hz), 12,27 (1H, s), of 13.75-14,05 (1H, usher.).

2-(4-Acetoxybenzoic)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: of 2.33 (3H, s), of 7.36-7,42 (2H, m), 7,47 (1H, TT, J = 7,3, 1.5 Hz), 7,51-to 7.59 (3H, m), 7,71-to 7.77 (2H, m), 8,00-of 8.06 (2H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,06 (1H, d, J = 2.0 Hz), 12,25 (1H, s), of 13.75-13,95 (1H, user.).

2-((E)-3-(4-Acetoxyphenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: to 2.29 (3H, s), 6,92 (1H, d, J = 15.7 Hz), 7,21 (2H, d, J = 8.7 Hz), 7,43-7,58 (4H, m), 7,66 (1H, d, J = 15.7 Hz), 7.68 per to 7.75 (2H, m), 7,81 (2H, d, J = 8.7 Hz), 8,10 (1H, d, J = 8,3 Hz), 8,98 (1H, d, J = 1.7 Hz), 11,43 (1H, s), 13,50-13,80 (1H, usher.).

2-((E)-3-(3-Methoxyphenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 3,82 (3H, s), of 6.96 (1H, d, J = 15.6 Hz), 6,97? 7.04 baby mortality (1H, m), 7,28-7,39 (3H, m), 7,43-7,58 (4H, m), a 7.62 (1H, d, J = 15.6 Hz), 7,71 (2H, d, J = 8.0 Hz), of 8.09 (1H, d, J = 8,3 G is), 8,97 (1H, d, J = 1.7 Hz), of 11.45 (1H, s).

2-((E)-3-(4-Chlorophenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 6,98 (1H, d, J = 15.7 Hz), 7,46 (1H, TT, J = 7,3, 1.5 Hz), of 7.48-EUR 7.57 (5H, m), of 7.64 (1H, d, J = 15.7 Hz), 7,69-7,74 (2H, m), to 7.77-7,83 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 8,98 (1H, d, J = 2.0 Hz), 11,43 (1H, s), 13,55-13,80 (1H, usher.).

2-((E)-3-(3-Chlorophenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: was 7.08 (1H, d, J = 15.6 Hz), 7,43-EUR 7.57 (6H, m), 7,63 (1H, d, J = 15.6 Hz), 7,69 to 7.75 (3H, m), 7,92 (1H, s), 8,10 (1H, d, J = 8.0 Hz), 8,98 (1H, d, J = 2.0 Hz), 11,42 (1H, s), 13,55-13,85 (1H, usher.).

2-((E)-3-(3,4-Dichlorophenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: for 7.12 (1H, d, J = 15.6 Hz), 7,46 (1H, TT, J = 7,3, 1.5 Hz), of 7.48-EUR 7.57 (3H, m), 7,63 (1H, d, J = 15.6 Hz), 7.68 per-7,74 (3H, m), to 7.77 (1H, DD, J = 8,5, 2.0 Hz), 8,10 (1H, d, J = 8,3 Hz)to 8.14 (1H, d, J = 2.0 Hz), 8,99 (1H, d, J = 1.7 Hz), 11,43 (1H, s), 13,55-13,80 (1H, usher.).

2-((E)-3-(Benzo[1,3]dioxol-5-yl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 6,10 (2H, s), for 6.81 (1H, d, J = 15.6 Hz), 6,98 (1H, d, J = 8.1 Hz), 7,21 (1H, DD, J = 8,1) and 1.7 Hz), 7,43-7,51 (3H, m), 7,51-to 7.61 (3H, m), 7.68 per-7,74 (2H, m), of 8.09 (1H, d, J = 8.1 Hz), of 9.00 (1H, d, J = 1.9 Hz), 11,37 (1H, s), 13,55-of 13.75 (1H, usher.).

4-Phenyl-2-((E)-3-(thiophene-2-yl)acrylamide)benzoic acid

1H-NMR (DMSO-d6) δ: 6,60 (1H, d, J = 15,4 Hz), 7,17 (1H, DD, J = 5,1, 3.6 Hz), 7,43-7,58 (5H, m), 7.68 per-7,74 (3H, m), 7,80 (1H, d, J = 15,4 Hz), 8,08 (1H, d, J = 8,3 Hz), of 8.90 (1H, d, J = 1.7 Hz), 11,30 (1H, s).

2-(4-Morpholinomethyl)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 3.27 to and 3.31 (4H, m), 3,74-of 3.77 (4H, m), 7,10 (2H, d, J = 9,0 Hz), 7,43-7,51 (2H, m), 7,51-7,58 (2H, m), 7,71-7,76 (2H, m), 7,86 (2H, d, J = 9.0 Hz), to 8.12 (1H, d, J = 8,3 Hz), 9,12 (1H, d, J = 1.7 Hz), 12,16 (1H, s).

2-(2-(4-Nitrophenyl)acetamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: a 4.03 (2H, s), 7,42-rate of 7.54 (4H, m), of 7.64-7,71 (4H, m), of 8.04 (1H, d, J = 8,3 Hz), by 8.22-of 8.27 (2H, m), 8,82 (1H, d, J = 1.7 Hz), 11,18 (1H, s).

2-((E)-3-(3-Nitrophenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7.23 percent (1H, d, J = 15,9 Hz), 7,43-7,58 (4H, m), 7,69-7,81 (4H, m), 8,10 (1H, d, J = 8,3 Hz), 8,20-of 8.28 (2H, m), 8,63 (1H, t, J = 1,8 Hz), 8,98 (1H, d, J = 1.7 Hz), to 11.52 (1H, s).

2-((E)-3-(4-Nitrophenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,20 (1H, d, J = 15.6 Hz), 7,46 (1H, TT, J = 7,3, 1,6 Hz), 7,50-EUR 7.57 (3H, m), 7,69-7,79 (3H, m), 8,02-8,07 (2H, m), 8,10 (1H, d, J = 8,3 Hz), compared to 8.26-8,32 (2H, m), 8,97 (1H, d, J = 1.7 Hz), 11,50 (1H, s).

4-Phenyl-2-(4-phenylbutyramide)benzoic acid

1H-NMR (DMSO-d6) δ: 1,91 is 2.01 (2H, m)2,44 (2H, t, J = 7,3 Hz)to 2.66 (2H, t, J = 7,7 Hz), 7,15-7,33 (5H, m), 7,42-of 7.48 (2H, m), 7,49-7,56 (2H, m), 7,66-7,71 (2H, m), of 8.06 (1H, d, J = 8,3 Hz), 8,86 (1H, d, J = 1.9 Hz), 11,22 (1H, C), 13,55-of 13.75 (1H, usher.).

4-Phenyl-2-((E)-4-phenyl-3-butanamide)benzoic acid

1H-NMR (DMSO-d6) δ: 3.40 in (2H, DD, J = 7,3, 1.2 Hz), of 6.45 (1H, dt, J = 15,9, 7,3 Hz), of 6.68 (1H, d, J = 15,9 Hz), 7,25 (1H, TT, J = 7,3, 1.5 Hz), 7,32-7,37 (2H, m), 7,41-of 7.55 (6H, m), 7,65-7,71 (2H, m), with 8.05 (1H, d, J = 8,3 Hz), 8,89 (1H, d, J = 2.0 Hz), to 11.28 (1H, s).

Example 368

1.3 ml of methylene chloride and 1.3 μl of N,N-dimethylformamide and 0,031 ml oxalicacid add sequentially to 69 mg of 6-(piperidine-1-yl)PI is one-3-carboxylic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution of 54 mg of tert-butyl 2-amino-4-phenylbenzoate in a mixture of 3.7 ml of methylene chloride and 0.22 ml of triethylamine, and the mixture is stirred at room temperature for 2 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-phenyl-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoate.

To the obtained tert-butyl-4-phenyl-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, and water is added, and regulate pH to 6.5 with a saturated aqueous solution of sodium bicarbonate. The solid is separated by filtration, to thereby obtain 56 mg of 4-phenyl-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,50-1,70 (6H, m), 3,65-and 3.72 (4H, m), of 6.99 (1H, d, J = 9.3 Hz), 7,43-7,58 (4H, m), 7,70-7,76 (2H, m), to 7.99 (1H, DD, J = 9,3, 2,6 Hz)to 8.12 (1H, d, J = 8,3 Hz), to 8.70 (1H, d, J = 2.6 Hz), 9,07 (1H, d, J = 1.7 Hz), a 12.05 (1H, s).

Primer

1.3 ml of methylene chloride and 1.3 μl of N,N-dimethylformamide and 0,031 ml oxalicacid add sequentially to 69 mg of 3,4-dimethoxyphenol acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution of 57 mg of tert-butyl 2-amino-4-phenoxybenzoate in a mixture of 3.7 ml of methylene chloride and 0.22 ml of triethylamine, and the mixture is stirred at room temperature for 2 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl 2-((E)-3-(3,4-acid)acrylamide)-4-phenoxybenzoate.

To the obtained tert-butyl 2-((E)-3-(3,4-acid)acrylamide)-4-phenoxybenzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 13 mg ((E)-2-(3-(3,4-acid)acrylamide)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d 6) δ: of 3.80 (3H, s), 3,83 (3H, s), 6,69-for 6.81 (2H, m), of 6.99 (1H, d, J = 8.5 Hz), 7,14-7,20 (2H, m), 7,22-7,31 (2H, m), 7,38 (1H, s), 7,45-7,51 (2H, m), 7,54 (1H, d, J = 15.6 Hz), 8,03 (1H, d, J = 8,8 Hz), scored 8.38 (1H, d, J = 2.4 Hz), 11,50 (1H, s), 13,40-13,60 (1H, usher.).

Examples 370-387

Compounds shown in table 36, receive the same manner as in example 369.

Table 36

Triptorelin 4 phenoxy-2-((E)-3-(pyridin-4-yl)acrylamide)benzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,8, and 2.6 Hz), 7,15-7,20 (2H, m), 7.23 percent-to 7.32 (2H, m), 7,45-7,53 (2H, m), the 7.65 (1H, d, J = 15.6 Hz), 7,94 (2H, d, J = 6.4 Hz), with 8.05 (1H, d, J = 8,8 Hz), a 8.34 (1H, d, J = 2.6 Hz), the rate of 8.75 (2H, d, J = a 5.1 Hz), 11,68 (1H, s).

4 Phenoxy-2-(5-(thiophene-2-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,83 (1H, DD, J = 8,8, and 2.6 Hz), 7,17-of 7.23 (2H, m), 7,25 (1H, DD, J = 5,1, and 3.7 Hz), 7,27-7,33 (1H, m), 7,47-rate of 7.54 (2H, m), of 7.75 (1H, DD, J = 5,1, 1.1 Hz), 7,78 (1H, DD, J = 3,7, 1.1 Hz), of 8.09 (1H, d, J = 8,8 Hz), 8.34 per (1H, d, J = 2.6 Hz), 8,43 (1H, t, J = 2.2 Hz), 8,98 (1H, d, J = 2.2 Hz), 9,14 (1H, d, J = 2.2 Hz), 12,51 (1H, s).

4 Phenoxy-2-(6-phenylpyrimidine-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,85 (1H, DD, J = 8,8, 2.4 Hz), 7,19-of 7.25 (2H, m), 7,31 (1H, t, J = 7.5 Hz), of 7.48-of 7.55 (2H, m), EUR 7.57-to 7.64 (3H, m), 8,10 (1H, d, J = 8,8 Hz), with 8.33 (2H, DD, J = 8,0, 1.7 Hz), charged 8.52 (1H, d, J = 2.4 Hz), at 8.60 (1H, d, J = 1.2 Hz), to 9.45 (1H, d, J = 1.2 Hz), 13,33 (1H, s), 13,35-of 13.75 (1H, usher.).

4 Phenoxy-2-(5-phenyl-1H-pyrazole-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: of 6.68 (1H, DD, J = 8,8, 2.7 Hz), 7,12-7,17 (2H, m), 7,24 (1H, t, J = 7.4 Hz), 7,32-7,52 (6H, m), of 7.64-of 7.70 (2H, m), 800 (1H, d, J = 8,8 Hz), 8,29 (1H, d, J = 2.7 Hz), 11,65-12,00 (1H, usher.), 13,35-of 13.75 (2H, usher.).

4 Phenoxy-2-(3-phenyl-1H-pyrazole-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,74 (1H, DD, J = 8,9, and 2.6 Hz), 7,16-7,24 (3H, m), 7,28 (1H, t, J = 7.4 Hz), 7,40 (1H, t, J = 7,3 Hz), 7,45-7,53 (4H, m), 7,82 (2H, d, J = 7,6 Hz), with 8.05 (1H, d, J = 8,9 Hz), 8,48-8,49 (1H, m), to 12.52 (1H, s), 13,30-13,55 (1H, usher.), 13,98 (1H, s).

4 Phenoxy-2-(3-phenylisoxazol-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: PC 6.82 (1H, DD, J = 8,9, and 2.6 Hz), 7.18 in-of 7.23 (2H, m), 7,27-7,33 (1H, m), 7,47 to 7.62 (6H, m), 7,94-8,02 (2H, m), 8,08 (1H, d, J = 8,9 Hz), scored 8.38 (1H, d, J = 2.6 Hz), 12,66 (1H, s).

2-(3-Acetoxybenzoic)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), is 6.78 (1H, DD, J = 8,9, 2.7 Hz), 7,15-7,22 (2H, m), 7,28 (1H, t, J = 7,6 Hz), 7,40 was 7.45 (1H, m), 7,46-7,53 (2H, m), to 7.61-to 7.68 (2H, m), 7,79-7,81 (1H, m), 8,07 (1H, d, J = 8,9 Hz), of 8.37 (1H, d, J = 2.7 Hz), 12,43 (1H, s), 13,65-13,85 (1H, usher.).

2-(2-Hydroxybenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6.75 in (1H, DDD, J = 8,8, of 2.5, and 0.9 Hz), 6,92-7,02 (2H, m), 7,14-7,19 (2H, m), 7.23 percent-7,29 (1H, m), 7,39-7,51 (3H, m), 7,80 (1H, d, J = 7,6 Hz), of 8.04 (1H, DD, J = 8,8, 0.9 Hz), to 8.41 (1H, DD, J = 2.5 and 0.9 Hz), to 11.31 (1H, ), 12,42 (1H, s).

2-(4-Acetoxybenzoic)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,31 (3H, s), is 6.78 (1H, DD, J = 8,9 and 2.5 Hz), 7,15-7,21 (2H, m), 7,26-7,31 (1H, m), 7,33-7,39 (2H, m), 7,46-7,53 (2H, m), 7,93-to 7.99 (2H, m), 8,07 (1H, d, J = 8,9 Hz), 8,39 (1H, d, J = 2.5 Hz), KZT 12.39 (1H, s), 13,60-13,80 (1H, usher.).

2-((E)-3-(3-Methoxyphenyl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 3,81 (3, C)6,74 (1H, DD, J = 8,8, and 2.6 Hz), to 6.88 (1H, d, J = 15.6 Hz), of 6.99 (1H, DD, J = 8,0, 1.5 Hz), 7,15-7,20 (2H, m), 7,25-7,38 (4H, m), 7,45-7,52 (2H, m), EUR 7.57 (1H, d, J = 15.6 Hz), 8,03 (1H, d, J = 8,8 Hz), 8,35 (1H, d, J = 2,6 Hz), to 11.56 (1H, s), 13,40-13,60 (1H, usher.).

2-((E)-3-(4-Chlorophenyl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,74 (1H, DD, J = 8,9, and 2.6 Hz), 6.89 in (1H, d, J = 15.6 Hz), 7,15-7,20 (2H, m), 7,28 (1H, t, J = 7.4 Hz), 7,45-7,52 (4H, m), 7,60 (1H, d, J = 15.6 Hz), 7,76-7,79 (2H, m), 8,03 (1H, d, J = 8,9 Hz), 8,35 (1H, d, J = the 2.6 Hz), 11,57 (1H, s), 13,40-13,65 (1H, usher.).

2-((E)-3-(3-Chlorophenyl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6.75 in (1H, DD, J = 8,9 and 2.5 Hz), of 6.99 (1H, d, J = 15.6 Hz), 7,14-7,20 (2H, m), 7,28 (1H, t, J = 7.4 Hz), 7,45-7,52 (4H, m), to 7.59 (1H, d, J = 15.6 Hz), 7,66-7,73 (1H, m), of 7.90 (1H, s), of 8.04 (1H, d, J = 8,9 Hz), 8,35 (1H, d, J = 2.5 Hz), 11,59 (1H, s).

2-((E)-3-(3,4-Dichlorophenyl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6.75 in (1H, DD, J = 9,0, 2.7 Hz),? 7.04 baby mortality (1H, d, J = 15.6 Hz), 7,15-7,21 (2H, m), 7,28 (1H, t, J = 7.4 Hz), 7,45-7,53 (2H, m), 7,58 (1H, d, J = 15.6 Hz), 7,69 (1H, d, J = 8.6 Hz), of 7.75 (1H, DD, J = 8,6, 2.0 Hz), 8,03 (1H, d, J = 9.0 Hz), to 8.12 (1H, d, J = 2.0 Hz), 8,35 (1H, d, J = 2.7 Hz), 11,60 (1H, s).

2-((E)-3-(Benzo[1,3]dioxol-5-yl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: between 6.08 (2H, s), 6,68-6,77 (2H, m), of 6.96 (1H, d, J = 8.0 Hz), 7,14-7,22 (3H, m), 7,25-7,31 (1H, m), 7,43-of 7.55 (4H, m), 8,02 (1H, d, J = 9.0 Hz), at 8.36 (1H, d, J = 2.7 Hz), 11,50 (1H, s).

4 Phenoxy-2-((E)-3-(thiophene-2-yl)acrylamide)benzoic acid

1H-NMR (DMSO-d6) δ: of 6.49 (1H, d, J = 15,4 Hz), was 6.73 (1H, DD, J = 9,0, 2,5 Hz), 7,13-7,19 (3H, m), 7,25-7,30 (1H, m), 7,44-7,54 3H, m), 7,71 (1H, d, J = 5,1 Hz), of 7.75 (1H, d, J = 15,4 Hz), 8,02 (1H, d, J = 9.0 Hz), 8,30 (1H, d, J = 2.5 Hz), 11,50 (1H, s).

2-(4-Morpholinomethyl)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: of 3.28 (4H, t, J = 4.9 Hz), 3,74 (4H, t, J = 4.9 Hz), 6,72 (1H, DD, J = 8,8, 2.4 Hz), 7,07 (2H, d, J = 9.0 Hz), 7,14-7,20 (2H, m), 7.24 to to 7.32 (1H, m), 7,45-7,52 (2H, m), 7,79 (2H, d, J = 9.0 Hz), with 8.05 (1H, d, J = 8,8 Hz), 8,43 (1H, d, J = 2.4 Hz), to 12.28 (1H, s), 13,50-13,70 (1H, usher.).

2-(2-(4-Nitrophenyl)acetamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: of 3.96 (2H, s)of 6.71 (1H, DD, J = 8,9 and 2.5 Hz), 7,09-to 7.15 (2H, m), 7,24 (1H, t, J = 7,3 Hz), 7,42-7,49 (2H, m), to 7.59-to 7.67 (2H, m), of 7.97 (1H, d, J = 8,9 Hz), 8,17 (1H, d, J = 2.5 Hz), 8,18-8,24 (2H, m), to 11.31 (1H, C), 13,40-13,55 (1H, usher.).

4 Phenoxy-2-((E)-4-phenyl-3-butanamide)benzoic acid

1H-NMR (DMSO-d6) δ: at 3.35 (2H, DD, J = 7,3, 1.0 Hz), 6,41 (1H, dt, J = 15,9, 7,3 Hz), only 6.64 (1H, d, J = 15,9 Hz), of 6.71 (1H, DD, J = 8,9, and 2.6 Hz), 7,11-7,17 (2H, m), 7.23 percent-7,29 (2H, m), 7,31-7,37 (2H, m), 7,43-to 7.50 (4H, m), to 7.99 (1H, d, J = a 8.9 Hz), compared to 8.26 (1H, d, J = 2.6 Hz), of $ 11.48 (1H, s), 13,40-13,60 (1H, usher.).

Example 388

0,059 ml of triethylamine and 65 mg of 5-(1H-pyrrol-1-yl)pyridine-3-carbonylchloride added sequentially to a solution containing 60 mg of tert-butyl 2-amino-4-phenoxybenzoate in 5.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture at room temperature successively added 0,029 ml of triethylamine and 22 mg of 5-(1H-pyrrol-1-yl)pyridine-3-carbonylchloride, and the mixture is peremeshivayte at room temperature for 1 hour. To the reaction mixture of 0.58 g aminomethylpropanol polystyrene and the mixture is stirred at room temperature over night. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-phenoxy-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido))benzoate.

To the obtained tert-butyl-4-phenoxy-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, add ethyl acetate and water, and regulate pH to 7.0 with a saturated aqueous solution of sodium bicarbonate. The organic layer is separated, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining 7,0 mg 4 phenoxy-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,37 (2H, t, J = 2.2 Hz), at 6.84 (1H, DD, J = 8,9, and 2.6 Hz), 7,17-7,22 (2H, m), 7,30 (1H, t, J = 7.4 Hz), 7,47-rate of 7.54 (2H, m), 7,58 (2H, t, J = 2.2 Hz), of 8.09 (1H, d, J = 8,9 Hz), 8,32 (1H, d, J 2.6 Hz), to 8.40 (1H, t, J = 2.2 Hz), of 8.92 (1H, d, J = 2.2 Hz), to 9.15 (1H, d, J = 2.2 Hz), 12,46 (1H, s).

Example 389

0.25 ml of acetic acid and 4.3 μl of 2.5-dimethoxytetrahydrofuran successively added to 10 mg of 2-(3-aminobenzamide)-4-vinylbenzoic acid at room temperature, and the mixture was stirred at 90°C for 5 minutes. To the reaction mixture are added ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure, thus obtaining 8,3 mg of 4-phenyl-2-(3-(1H-pyrrol-1-yl)benzamido)benzoic acid as a brown solid.

1H-NMR (DMSO-d6) δ: 6,34 (2H, t, J = 2.1 Hz), 7,45-7,51 (3H, m), 7,53-to 7.59 (3H, m), of 7.69 (1H, t, J = 7.9 Hz), 7,73 for 7.78 (2H, m), 7,82-of 7.90 (2H, m), 8,11-8,18 (2H, m), the remaining 9.08 (1H, d, J = 1.7 Hz), 12,37 (1H, s).

Example 390

0,062 ml of triethylamine and 69 mg of 5-(1H-pyrrol-1-yl)pyridine-3-carbonylchloride added sequentially to a solution containing 60 mg of tert-butyl 2-amino-4-phenylbenzoate in 5.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture at room temperature successively added 0,031 ml of triethylamine and 22 mg of 5-(1H-pyrrol-1-yl)pyridine-3-carbonylchloride is a, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture of 0.62 g aminomethylpropanol polystyrene, and the mixture is stirred at room temperature over night. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-phenyl-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido))benzoate.

To the obtained tert-butyl-4-phenyl-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido))benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, add ethyl acetate and water, and regulate pH to 7.0 with a saturated aqueous solution of sodium bicarbonate. The organic layer is separated, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 23 mg of 4-phenyl-2-(5-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,39 (2H, t, J = 2.2 Hz), 7,45-7,51 (1H, m), 7,53-to 7.61 (5H, m), 7,73-to 7.77 (2H, m), 8,15 (1H, d, J = 8,3 Hz), of 8.47 (1H, t, J = 2.4 Hz), 8,97-of 9.02 (2H, m), 9,17 (1H, d, J = 2.4 Hz), of 12.26 (1H, s).

Example 391

The following connection receive the same manner as in example 390.

4-Phenyl-2-(2-pyrrolidin-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 1,80-1,89 (4H, m), 3,35-3,44 (4H, m), 6,74 (1H, DD, J = 7,4, a 4.9 Hz), 7,44-7,58 (4H, m), 7,69-7,74 (2H, m), 7,83 (1H, DD, J = 7,4, 1.8 Hz), 8,10 (1H, d, J = 8,3 Hz), 8,24 (1H, DD, J = 4,9, 1.8 Hz), of 9.02 (1H, s), 11,67 (1H, s).

Example 392

0,056 ml of triethylamine and 45 mg ((E)-2-phenylphenyl)sulphonylchloride added sequentially to a solution containing 54 mg of tert-butyl 2-amino-4-phenylbenzoate in 3.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture at room temperature successively added 0,028 ml of triethylamine and 8.1 mg ((E)-2-phenylphenyl)sulphonylchloride, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-phenyl-2-(((E)-2-phenylphenyl)sulphonamido))benzoate.

To the resulting TP is t-butyl-4-phenyl-2-(((E)-2-phenylphenyl)sulphonamido)benzoate add 10 ml triperoxonane acid, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 26 mg of 4-phenyl-2-(((E)-2-phenylphenyl)sulphonamido))benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,39-7,58 (8H, m), to 7.61-7,66 (2H, m), 7,73-7,81 (4H, m), with 8.05 (1H, d, J = 8,3 Hz), 11,04 (1H, s).

Examples 393, 394

Compounds shown in table 37, receive the same manner as in example 392.

Table 37

2-(Benzylmaleimide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 4,78 (2H, s), 7.23 percent-7,33 (5H, m), 7,41-7,49 (2H, m), 7,50-7,56 (2H, m), 7,60-the 7.65 (2H, m), to 7.67 (1H, d, J = 1.7 Hz), with 8.05 (1H, d, J = 8,3 Hz), 10,75-10,90 (1H, usher.).

2-(3-Bromobenzene)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,44 is 7.50 (1H, m), 7,51-7,63 (4H, m), 7,70-to 7.77 (2H, m), a 7.85-of 7.90 (1H, m), 7,95-8,00 (1H, m), 8,10-8,16 (2H, m), 8,99 (1H, d, J = 1.7 Hz), of 12.26 (1H, s), of 13.75-14,00 (1H, usher.).

Example 395

0,056 ml of triethylamine and 61 mg ((E)-2-phenylphenyl)sulphonylchloride successively added to a solution containing 57 mg of tert-butyl 2-amino-4-phenoxybenzoate in 5.0 ml of methylene chloride, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous solution is of hydrocarbonate sodium, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-phenoxy-2-(((E)-2-phenylphenyl)sulphonamido)benzoate.

10 ml triperoxonane acids are added to the obtained tert-butyl-4-phenoxy-2-(((E)-2-phenylphenyl)sulphonamido)benzoate, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, while receiving 17 mg of 4-phenoxy-2-(((E)-2-phenylphenyl)sulphonamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 6.68 (1H, DD, J = 8,8, 2.4 Hz), of 6.99 (1H, d, J = 2.4 Hz),? 7.04 baby mortality-to 7.09 (2H, m), 7.23 percent-7,29 (1H, m), 7,32-7,51 (7H, m), of 7.64-of 7.70 (2H, m), 7,98 (1H, d, J = 8,8 Hz), 11,16 (1H, s).

Example 396

2.0 ml of methylene chloride, 3,9 μl of N,N-dimethylformamide and 0.094 ml of oxalicacid successively added to 206 mg 4-ecotoxicology acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution of 86 mg of tert-butyl 2-amino-4-phenoxybenzoate in a mixture of 3.0 ml of methylene chloride and 0.67 ml of triethylamine, and the mixture was stirred at on the th temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl 2-((E)-3-(4-acetoxyphenyl)acrylamide)-4-phenoxybenzoate.

10 ml triperoxonane acids are added to the obtained tert-butyl 2-((E)-3-(4-acetoxyphenyl)acrylamide)-4-phenoxybenzoate, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 60-100% acetonitrile/0.1% of triperoxonane acid], while receiving 34 mg of 2-((E)-3-(4-acetoxyphenyl)acrylamide)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,28 (3H, s), 6,74 (1H, DD, J = 8,9 and 2.5 Hz), 6,83 (1H, d, J = 15.6 Hz), 7,14-of 7.23 (4H, m), 7,25-7,31 (1H, m), 7,45-7,52 (2H, m), to 7.61 (1H, d, J = 15.6 Hz), 7,76-of 7.82 (2H, m), 8,03 (1H, d, J = 8,9 Hz), 8,35 (1H, d, J = 2.5 Hz), 11,58 (1H, s), 13,40-13,65 (1H, usher.).

Example 397

2.0 ml of methylene chloride, 3,9 μl of N,N-dimethylformamide and 0.094 ml of oxalicacid successively added to 180 mg of 2-acetoxybenzoic acid at room temperature, and the mixture paramashiva the t at the same temperature for 1 hour. The reaction mixture was added to a solution of 81 mg of tert-butyl 2-amino-4-phenylbenzoate in a mixture of 3.0 ml of methylene chloride and 0.67 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2-acetoxybenzoic)-4-phenylbenzoate.

10 ml triperoxonane acids are added to the obtained tert-butyl 2-(2-acetoxybenzoic)-4-phenylbenzoate, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue successively added to 0.50 ml of methanol, and 0.50 ml of tetrahydrofuran and 6.1 mg of potassium carbonate, and the mixture is stirred at room temperature for 2 hours. To the reaction mixture is added 10% aqueous citric acid solution, and the solid is separated by filtration, thus obtaining 8.2 mg of 2-(2-hydroxybenzamide)-4-vinylbenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 6.96-7,05 (2H, m), 7,42-7,49 (2H, m), 7,49-7,58 (3H, m), 7,71-7,76 (2H, m), 7,89-to 7.93 (1H, m), 8,10 (1H, d, J = 8,3 Hz), of 9.02 (1H, d, J = 1.7 Hz), 11,46 (1H, s), 12,32 (1H, s).

Por the measures 398

0,50 ml of methanol, and 0.50 ml of tetrahydrofuran and 8.3 mg of potassium carbonate successively added to 15 mg of 2-(3-acetoxybenzoic)-4-vinylbenzoic acid at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture is added 10% aqueous citric acid solution, and the solid is separated by filtration, while receiving 12 mg of 2-(3-hydroxybenzamide)-4-vinylbenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,00-7,07 (1H, m), 7,35-to 7.59 (7H, m), 7,73 (2H, d, J = 7,6 Hz)to 8.14 (1H, d, J = 8.0 Hz), the remaining 9.08 (1H, d, J = 1.4 Hz), 9,92 (1H, s), 12,22 (1H, s).

Examples 399, 400

Compounds shown in table 38, receive the same manner as in example 398.

Table 38

2-(4-Hydroxybenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 6,94 (2H, d, J = 8,8 Hz), 7,43-7,51 (2H, m), 7,54 (2H, t, J = 7,6 Hz), 7,70-7,76 (2H, m), a 7.85 (2H, d, J = 8,8 Hz), 8,13 (1H, d, J = 8,3 Hz), which is 9.09 (1H, d, J = 1.7 Hz), 10,29 (1H, s), 12,16 (1H, s).

2-((E)-3-(4-Hydroxyphenyl)acrylamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: to 6.67 (1H, d, J = 15.6 Hz), PC 6.82 (2H, d, J = 8.5 Hz), 7,43-to 7.50 (2H, m), 7,50 to 7.62 (5H, m), 7.68 per-7,74 (2H, m), of 8.09 (1H, d, J = 8,3 Hz), of 9.00 (1H, d, J = 2.0 Hz), 9,98 (1H, s), 11,37 (1H, s), 13,50-13,80 (1H, user.).

Example 401

0,50 ml of methanol, and 0.50 ml of tetrahydrofuran and 4.2 mg of potassium carbonate sequence until ablaut to 8.0 mg of 2-(3-acetoxybenzoic)-4-phenoxybenzoic acid at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture is added 10% aqueous citric acid solution, and the solid is separated by filtration, thus obtaining 4.4 mg of 2-(3-hydroxybenzamide)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,76 (1H, DD, J = 8,8, 2.7 Hz), 7,02 (1H, DDD, J = 7,6, 2,3, 1.5 Hz), 7,15-7,21 (2H, m), 7,25-7,40 (4H, m), 7,46-7,52 (2H, m), 8,07 (1H, d, J = 8,8 Hz), to 8.41 (1H, d, J = 2.7 Hz), for 9.90 (1H, s), 12,34 (1H, s), 13,55-of 13.75 (1H, usher.).

Examples 402, 403

Compounds shown in table 39, receive the same manner as in example 401.

Table 39

2-(4-Hydroxybenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: was 6.73 (1H, DD, J = 8,8, 2.4 Hz), 6,91 (2H, d, J = 8,8 Hz), 7,15-7,19 (2H, m), 7,27 (1H, t, J = 7.4 Hz), 7,45-7,52 (2H, m), 7,78 (2H, d, J = 8,8 Hz), with 8.05 (1H, d, J = 8,8 Hz), to 8.41 (1H, d, J = 2.4 Hz), 10,28 (1H, ), 12,27 (1H, s).

2-((E)-3-(4-Hydroxyphenyl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: return of 6.58 (1H, d, J = 15.6 Hz), of 6.71 (1H, DD, J = 8,8, and 2.6 Hz), to 6.80 (2H, d, J = 8.6 Hz), 7,13-7,19 (2H, m), 7.24 to 7,30 (1H, m), 7,44-7,53 (3H, m), 7,56 (2H, d, J = 8.6 Hz), 8,02 (1H, d, J = 8,8 Hz), 8,35 (1H, d, J = the 2.6 Hz), becomes 9.97 (1H, s), 11,60 (1H, s).

Example 404

3.0 ml of methanol, 2.0 ml of ethyl acetate and 4.0 mg of 5% palladium on coal is added to 20 mg of 2-(4-nitrobenzamide)-4-phenoxybenzoic acid at room temperature, and the mixture is stirred in an atmosphere of water the ode at 40°C for 8 hours. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure, thus obtaining 20 mg of 2-(4-aminobenzamide)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,57-of 6.65 (3H, m), 7,07-7,13 (2H, m), 7,20 (1H, t, J = 7.4 Hz), 7,41-7,46 (2H, m), to 7.67 (2H, d, J = 8,8 Hz), 8,02 (1H, d, J = 8.6 Hz), 8,39 (1H, d, J = 2,4 Hz).

Example 405

2.0 ml of methanol, 2.0 ml of ethyl acetate and 3.0 mg of 5% palladium on coal added to 15 mg of 2-(3-nitrobenzamide)-4-vinylbenzoic acid at room temperature, and the mixture is stirred in hydrogen atmosphere at 40°C for 2 hours. Insoluble matter is removed by filtration, and the solvent is evaporated under reduced pressure, thus obtaining 5.1 mg of 2-(3-aminobenzamide)-4-vinylbenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,74-for 6.81 (1H, m), 7,13-7,22 (3H, m), of 7.36 (1H, DD, J = 8,1) and 1.7 Hz), 7,42 (1H, t, J = 7,3 Hz), 7,49-rate of 7.54 (2H, m), 7,66-7,72 (2H, m), 8,10 (1H, d, J = 8.1 Hz), 9,05 (1H, d, J = 1.7 Hz).

Example 406

0,019 ml of 1H-pyrrole, 0.12 g of cesium carbonate, 5.1 mg of Tris(dibenzylideneacetone)diplegia(0), 1.6 mg three-tert-butylperbenzoate and 4.4 mg of 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate 1.4 ml of toluene, at room temperature, and formed of coscipata under reflux in nitrogen atmosphere for 3 hours. After cooling the reaction mixture to room temperature, add 5.1 mg of Tris(dibenzylideneacetone)diplegia(0), 1.6 mg three-tert-butylperbenzoate and 4.4 mg of 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl, and the resulting mixture is refluxed for 3 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 10:1], while receiving 60 mg of tert-butyl 2-(benzamido)-4-(1H-pyrrol-1-yl)benzoate as a white solid.

1H-NMR (CDCl3) δ: 1,65 (9H, s)6,38 (2H, t, J = 2.2 Hz), 7,12 (1H, DD, J = 8,6, and 2.3 Hz), 7,25-7,28 (2H, m), 7,51-to 7.61 (3H, m), 8,05-8,10 (3H, m), 9,16 (1H, d, J = 2.3 Hz), 12,36 (1H, s).

Example 407

33 mg of 1H-indole, 0.12 g of cesium carbonate, 5.1 mg of Tris(dibenzylideneacetone)diplegia(0), 1.6 mg three-tert-butylperbenzoate and 4.4 mg of 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl added to a solution containing 70 mg of tert-butyl 2-(benzamid is)-4-bromobenzoate 1.4 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 4 hours. After cooling the reaction mixture to room temperature, add 33 mg of 1H-indole, 79 mg tribalista, 5.1 mg of Tris(dibenzylideneacetone)diplegia(0), 1.6 mg three-tert-butylperbenzoate and 4.4 mg of 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl, and the resulting mixture is refluxed for 4 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 20:1], while receiving 45 mg of tert-butyl 2-(benzamido)-4-(1H-indol-1-yl)benzoate as a colourless oil.

1H-NMR (CDCl3) δ: rate of 1.67 (9H, s), of 6.73 (1H, d, J = 3,4 Hz), 7.18 in-7,22 (1H, m), 7,25-7,33 (2H, m), of 7.48 (1H, d, J = 3,4 Hz), 7,51 to 7.62 (3H, m), 7,66-of 7.70 (1H, m), 7,83 (1H, d, J = 8,3 Hz), 8,06-8,10 (2H, m), 8,17 (1H, d, J = 8,8 Hz), which 9.22 (1H, d, J = 2.2 Hz), 12,35 (1H, s).

Example 408

The following connection get the same with the special as in example 200.

tert-Butyl 2-(benzamido)-4-(3,4-acid)benzoic acid

1H-NMR (CDCl3) δ: 1,65 (9H, s), of 3.94 (3H, s)to 3.99 (3H, s), of 6.96 (1H, d, J = 8,3 Hz), 7.23 percent (1H, d, J = 2.2 Hz), 7,28-7,34 (2H, m), 7,51-to 7.61 (3H, m), 8,04-8,11 (3H, m), which 9.22 (1H, d, J = 2.0 Hz), 12,27 (1H, s).

Example 409

of 0.24 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l are added to a solution containing 58 mg of tert-butyl 2-(benzamido)-4-(1H-pyrrol-1-yl)benzoate in a mixture of 1.0 ml of dioxane and 1.0 ml of methanol, and the mixture was stirred at 50°C for 1 hour and 30 minutes. After cooling the reaction mixture to room temperature, water is added and after setting the pH to 3.0 with hydrochloric acid with a concentration of 1.0 mol/l is added ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with water and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 41 mg of 2-(benzamido)-4-(1H-pyrrol-1-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,37 (2H, t, J = 2.2 Hz), 7,41-7,47 (3H, m), to 7.59-7,71 (3H, m), of 7.96-8,02 (2H, m)to 8.12 (1H, d, J = 8.5 Hz), 8,96 (1H, d, J = 2.2 Hz), 12,40 (1H, s).

Example 410

The following connection receive in the same way as the example 409.

2-(Benzamido)-4-(1H-indol-1-yl)benzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 3,4, 0.5 Hz), 7.18 in-7,24 (1H, m), 7,28-7,33 (1H, m), 7,47 (1H, DD, J = 8,6, 2.4 Hz), to 7.59-7,73 (4H, m), 7,79 (1H, d, J = 3,4 Hz), the 7.85 (1H, DD, J = 8,4, 0.6 Hz), 7,98-8,03 (2H, m), 8,24 (1H, d, J = 8.6 Hz), which is 9.09 (1H, d, J = 2.4 Hz), 12,46 (1H, s).

Example 411

The following connection receive the same manner as in example 211.

2-(Benzamido)-4-(3,4-acid)benzoic acid

1H-NMR (DMSO-d6) δ: a 3.83 (3H, s), a 3.87 (3H, s), 7,12 (1H, d, J = 9.0 Hz), 7,27-to 7.32 (2H, m), 7,52 (1H, DD, J = 8,3, 1.8 Hz), 7,58-of 7.70 (3H, m), 7,97-8,02 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 9,04 (1H, d, J = 1,8 Hz), of 12.26 (1H, s).

Example 412

55 mg of 2-nitroaniline, 0.17 g of cesium carbonate, 2.4 mg of Tris(dibenzylideneacetone)diplegia(0), 1.2 mg of palladium acetate and 6.3 mg 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl added to a solution containing 0.10 g of tert-butyl 2-(benzamido)-4-bromobenzoate in 2.0 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 4 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 1:1], while receiving 94 mg of tert-butyl 2-(benzamido)-4-(2-nitroaniline)benzoate as a yellow solid.

1H-NMR (CDCl3) δ: 1,64 (9H, s), 6.90 to-of 6.96 (2H, m), 7,50-of 7.60 (4H, m), 7,66 (1H, DD, J = 8,5, 1.2 Hz), 8,02 (1H, d, J = 8.5 Hz), 8,02-8,08 (2H, m), by 8.22 (1H, DD, J = 8,7, 1,6 Hz), to 8.94 (1H, d, J = 2.2 Hz), at 9.53 (1H, s), of 12.33 (1H, C).

Example 413

10 mg of 5% palladium on coal are added to a solution containing 50 mg of tert-butyl 2-(benzamido)-4-(2-nitroaniline)benzoate in a mixture of 4.0 ml of methanol and 8.0 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 1 hour and 30 minutes. After removing insoluble substances by filtration, the solvent is evaporated under reduced pressure, to thereby obtain 46 mg of tert-butyl 4-(2-aminoaniline)-2-(benzamido)benzoate as a pale yellow solid.

1H-NMR (CDCl3) δ: equal to 1.59 (9H, s), with 3.79 (2H, s), 5,67 (1H, s), 6,30 (1H, DD, J = 8,8, 2.3 Hz), 6,76-6,85 (2H, m), 7,06 for 7.12 (1H, m), 7,15-to 7.18 (1H, m), 7,49-7,58 (3H, m), a 7.85 (1H, d, J = 8,8 Hz), 8,03-8,08 (2H, m), to 8.41 (1H, d, J = 2.3 Hz), 12,41 (1H, s).

Example 414

28 mg of the acetate of formamidine added to a solution containing 44 mg of tert-butyl 4-(2-aminoaniline)-2-(benzamido)benzoate in 1.0 ml nanometrology ether of ethylene glycol, when the room is Noah temperature, and the mixture is stirred at 80°C for 3 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and water. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 1:1], while receiving 36 mg of tert-butyl 2-(benzamido)-4-(1H-benzimidazole-1-yl)benzoate as a pale yellow oil.

1H-NMR (CDCl3) δ: 1,68 (9H, s), 7.24 to 7,30 (1H, m), 7,34-7,44 (2H, m), 7,53-7,63 (3H, m), 7,78-of 7.82 (1H, m), 7,87-a 7.92 (1H, m), 8,06-8,10 (2H, m), 8,23 (1H, d, J = 8.6 Hz), compared to 8.26 (1H, s), of 9.30 (1H, d, J = 2.2 Hz), 12,38 (1H, ).

Example 415

A solution containing 34 mg of tert-butyl 2-(benzamido)-4-(1H-benzimidazole-1-yl)benzoate in 5.0 ml triperoxonane acid, stirred at room temperature for 1 hour and 30 minutes. The solvent is evaporated under reduced pressure and the obtained residue is added methanol, and the solid is separated by filtration, while receiving 24 mg of 2-(benzamido)-4-(1H-benzimidazole-1-yl)benzoic acid as a white solid.

0.5 ml triperoxonane acid and 0.01 ml Rast is ora 4.0 mol/l hydrogen chloride in dioxane successively added to 1.0 ml of the suspension, containing 15 mg of 2-(benzamido)-4-(1H-benzimidazole-1-yl)benzoic acid in ethyl acetate under ice cooling, and the mixture was stirred at the same temperature for 10 minutes. The solid is separated by filtration, while receiving 12 mg of the hydrochloride of 2-(benzamido)-4-(1H-benzimidazole-1-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,46-7,56 (2H, m), to 7.59-7,72 (4H, m), 7,87-a 7.92 (2H, m), 7,98-8,03 (2H, m), 8,32 (1H, d, J = 8.6 Hz), to 9.15 (1H, d, J = 2.2 Hz), 9,16 (1H, s), 12,38 (1H, s).

Examples 416-425

Compounds shown in table 40, receive the same manner as in example 251.

Table 40

2-(Benzamido)-4-(3-chloro-4-forfinal)benzoic acid

1H-NMR (DMSO-d6) δ: 7,52-of 7.70 (5H, m), 7,72-7,79 (1H, m), to 7.93 (1H, DD, J = 7,1, 2.4 Hz), of 7.96-8,02 (2H, m), 8,13 (1H, d, J = 8,3), 9,03 (1H, s), 12,23 (1H, s).

2-(Benzamido)-4-(3,4-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: rate of 7.54 (1H, DD, J = 8,3) and 1.7 Hz), 7,56-of 7.70 (5H, m), 7,78-7,86 (1H, m), of 7.96-with 8.05 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 9,04 (1H, d, J = 1.7 Hz), 12,22 (1H, s).

2-(Benzamido)-4-(2,5-differenl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,33-7,52 (4H, m), 7,58-of 7.70 (3H, m), 7,95-of 8.00 (2H, m), 8,16 (1H, d, J = 8,3 Hz), 8,96-8,99 (1H, m), 12,25 (1H, s).

2-(Benzamido)-4-(2,4-dichlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,28 (1H, DD, J = 8,3) and 1.7 Hz), 7,52 (1H, d, J = 8,3 Hz), 7,56-of 7.70 (4H, m), 7,80 (1H, d, J = 2.2 Hz), 7,94-of 8.00 (2H, m), 8,15 (1H, d, J = 8,3 Hz), 8,82 (1H, d, J = 1.7 Hz), 12,27 (1H, s).

p> 2-(Benzamido)-4-(4-fluoro-2-were)benzoic acid

1H-NMR (DMSO-d6) δ: 2,30 (3H, s), 7,11-of 7.25 (3H, m), 7,32 (1H, DD, J = 8,5, 6,1 Hz), EUR 7.57-of 7.69 (3H, m), 7,94-to 7.99 (2H, m)to 8.12 (1H, d, J = 8.1 Hz), 8,72 (1H, d, J = 1.7 Hz), of 12.26 (1H, s).

2-(Benzamido)-4-(2-trifloromethyl)benzoic acid

1H-NMR (DMSO-d6) δ: to 7.32 (1H, DD, J = 8,1, 1,6 Hz), 7,52-7,69 (7H, m), 7,95-of 8.00 (2H, m), 8,16 (1H, d, J = 8.1 Hz), 8,91 (1H, d, J = 1.6 Hz), 12,27 (1H, s).

2-(Benzamido)-4-(3,4-dimetilfenil)benzoic acid

1H-NMR (DMSO-d6) δ: to 2.29 (3H, s), of 2.33 (3H, s), 7,29 (1H, d, J = 7.8 Hz), 7,43-7,53 (3H, m), 7,58-of 7.70 (3H, m), of 7.96-8,02 (2H, m), 8,11 (1H, d, J = 8,3 Hz), 9,06 (1H, d, J = 1.7 Hz), 12,27 (1H, s).

2-(Benzamido)-4-(3-chloro-4-methoxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.94 (3H, s), 7,32 (1H, d, J = 8.7 Hz), 7,52 (1H, DD, J = 8,3, 1.8 Hz), 7,58-7,74 (4H, m), 7,79 (1H, d, J = 2.2 Hz), of 7.96-8,02 (2H, m), 8,11 (1H, d, J = 8,3 Hz), 9,04 (1H, d, J = 1,8 Hz), of 12.26 (1H, s), 13,70-13,95 (1H, usher.).

2-(Benzamido)-4-(2,3-dichlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,29 (1H, DD, J = 8,1) and 1.7 Hz), was 7.45 (1H, DD, J = 7,8) and 1.7 Hz), 7,51 (1H, t, J = 7.8 Hz), 7,58-of 7.69 (3H, m), of 7.75 (1H, DD, J = 7,8) and 1.7 Hz), 7,94-to 7.99 (2H, m), 8,15 (1H, d, J = 8.1 Hz), 8,80-8,83 (1H, m), 12,27 (1H, C).

2-(Benzamido)-4-(2,5-dichlorophenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 7,30 (1H, DD, J = 8,2, 1,6 Hz), 7,54-of 7.70 (6H, m), 7,94-of 8.00 (2H, m), 8,15 (1H, d, J = 8,2 Hz), 8,83 (1H, d, J = 1.6 Hz), 12,25 (1H, s).

Example 426

0,031 ml of 2-chloro-4-iodotoluene, 39 mg of sodium bicarbonate, 0.6 ml of ethanol, 0.3 ml of water and 11 mg tetranitroaniline)palladium(0) are added to a solution, containing 79 mg of tert-butyl 2-(benzamido)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate in 1.6 ml of toluene, at room temperature, and the resulting mixture is refluxed for 8 hours. After cooling the reaction mixture to room temperature, add 11 mg of tetrakis(triphenylphosphine)palladium(0) and the resulting mixture is refluxed for 7 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and water. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 10:1], while receiving tert-butyl-2-(benzamido)-4-(3-chloro-4-were)benzoate as a white solid.

5.0 ml triperoxonane acids are added to the obtained tert-butyl 2-(benzamido)-4-(3-chloro-4-were)benzoate, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added methanol, and the solid is separated by filtration, while receiving 14 mg of 2-(benzamido)-4-(3-chloro-4-were)benzoic acid in the form of the aircraft the CSO solids.

1H-NMR (DMSO-d6) δ: 2,40 (3H, s), 7,50-of 7.70 (6H, m), 7,76 (1H, d, J = 1.7 Hz), 7,97-8,02 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 9,06 (1H, d, J = 1.7 Hz), of 12.26 (1H, s).

Examples 427-429

Compounds shown in table 41, receive the same manner as in example 252.

Table 41

2-(Benzamido)-4-(3-chloro-2-were)benzoic acid

1H-NMR (DMSO-d6) δ: to 2.29 (3H, s), 7,20 (1H, DD, J = 8,3, 1.8 Hz), 7,26 (1H, DD, J = 7,7, 1.2 Hz), 7,35 (1H, DD, J = 7,9, 7,7 Hz), 7,53 (1H, DD, J = 7,9, 1.2 Hz), 7,58-of 7.69 (3H, m), 7,94-to 7.99 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 8,70-8,72 (1H, m), 12,29 (1H, s).

2-(Benzamido)-4-(5-chloro-2-were)benzoic acid

1H-NMR (DMSO-d6) δ: of 2.26 (3H, s), 7.23 percent (1H, DD, J = 8,2) and 1.7 Hz), 7,32 (1H, d, J = 1.7 Hz), 7,37-7,44 (2H, m), 7,58-of 7.70 (3H, m), 7,94-of 8.00 (2H, m), 8,13 (1H, d, J = 8,2 Hz), 8,73 (1H, d, J = 1.7 Hz), 12,25 (1H, s).

2-(Benzamido)-4-(5-chloro-2-methoxyphenyl)benzoic acid

1H-NMR (DMSO-d6) δ: 3,81 (3H, s), 7,21 (1H, d, J = 8,8 Hz), 7,34 (1H, DD, J = 8,2) and 1.7 Hz), 7,38 (1H, d, J = 2.7 Hz), of 7.48 (1H, DD, J = 8,8, 2.7 Hz), 7,58-of 7.69 (3H, m), 7,95-of 8.00 (2H, m), of 8.09 (1H, d, J = 8,2 Hz), 8,86 (1H, d, J = the 1.7 Hz), 12,21 (1H, s).

Example 430

2.0 ml of methylene chloride, and 2.7 μl of N,N-dimethylformamide and 0,061 ml oxalicacid successively added to 0,13 g of 3,5-dichlorobenzoyl acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution of 60 mg of tert-butyl 2-amino-4-penicillinate in a mixture of 3.0 ml of methyl is of chloride and 0.45 ml of triethylamine, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(3,5-dichlorobenzamide)-4-venetianskt.

10 ml triperoxonane acids are added to the obtained tert-butyl-2-(3,5-dichlorobenzamide)-4-penicillinate, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 62 mg of 2-(3,5-dichlorobenzamide)-4-venetiancasino acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,89-to 3.02 (4H, m), 7,12 (1H, DD, J = 8,0, 1.7 Hz), 7,16-7,21 (1H, m), 7.24 to 7,31 (4H, m), to $ 7.91-of 7.97 (4H, m), 8,48-charged 8.52 (1H, m), 12,14 (1H, s), 13,65-13,85 (1H, usher.).

Examples 431-439

Compounds shown in table 42, receive the same manner as in example 430.

Table 42

2-(3,4-Dichlorobenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,89-to 3.02 (4H, m), 7,11 (1H, DD, J = 8,1, 1.5 Hz), 7,16-7,21 (1H, m), 7.24 to 7,31 (4H, m), 7,88-to $ 7.91 (2H, m), and 7.9 (1H, d, J = 8.1 Hz), 8,13 (1H, s), 8,54 (1H, d, J = 1.5 Hz), 12,17 (1H, s), 13,60-13,85 (1H, usher.).

2-(3,5-Differentaite)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,88-to 3.02 (4H, m), 7,12 (1H, DD, J = 8,1, 1,6 Hz), 7,15-7,21 (1H, m), 7.23 percent-to 7.32 (4H, m), 7,56-7,66 (3H, m), of 7.96 (1H, d, J = 8.1 Hz), charged 8.52 (1H, d, J = 1.6 Hz), 12,12 (1H, s), 13,60-13,80 (1H, usher.).

2-(3,4-Differentaite)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,88-to 3.02 (4H, m), 7,10 (1H, DD, J = 8,1) and 1.7 Hz), 7,16-7,21 (1H, m), 7.24 to 7,31 (4H, m), 7,66-7,74 (1H, m), 7,79-a 7.85 (1H, m), to $ 7.91-to 7.99 (2H, m), 8,55 (1H, d, J = 1.7 Hz), 12,12 (1H, s), 13,60-13,80 (1H, usher.).

2-(3,5-Dimethylbenzamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: is 2.37 (6H, s), 2,88-to 3.02 (4H, m), 7,07 (1H, DD, J = 8,1, 1.5 Hz), 7,16-7,21 (1H, m), 7.24 to 7,31 (5H, m), EUR 7.57 (2H, s), 7,95 (1H, d, J = 8.1 Hz), 8,66-8,68 (1H, m), 12,19 (1H, s), 13,65-13,80 (1H, usher.).

2-(4-Acetoxybenzoic)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,32 (3H, s) 2,89-to 3.02 (4H, m), to 7.09 (1H, DD, J = 8,3, 1,6 Hz), 7,16-7,21 (1H, m), 7,25-to 7.32 (4H, m), 7,35-7,40 (2H, m), of 7.96 (1H, d, J = 8,3 Hz), of 7.96-8,03 (2H, m), 8,63-8,65 (1H, m), 12,17 (1H, s), 13,60-of 13.75 (1H, usher.).

4-Phenethyl-2-(6-phenylpyrimidine-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,92 was 3.05 (4H, m), 7,12-7,22 (2H, m), 7,25-to 7.32 (4H, m), 7,58-to 7.67 (3H, m), to 7.99 (1H, d, J = 8,3 Hz), 8,30-of 8.37 (2H, m)8,64 (1H, d, J = 1.2 Hz), 8,82 (1H, d, J = 1.5 Hz), for 9.47 (1H, d, J = 1.2 Hz), 13,16 (1H, C).

4-Phenethyl-2-(3-phenylisoxazol-5-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,90 totaling 3.04 (4H, m), 7,12-7,21 (2H, m), 7,25-to 7.32 (4H, m), 7,52-7,63 (4H, m), of 7.96-8,02 (3H, m), 8,63 (1H, d, J = 1.4 Hz), 12,49 (1H, s)

4-Phenethyl-2-((E)-4-phenyl-3-butanamide)benzoic acid

1H-NMR (DMSO-d6) δ: 2,84-of 2.97 (4H, m), 3,35-to 3.38 (2H, m), 6,40-6,50 (1H, m), of 6.66 (1H, d, J = 15,8 Hz), 7,01 (1H, DD, J = 8.0 a, 1,6 Hz), 7,14-7,20 (1H, m), 7,21-7,30 (5H, m), 7,31-7,38 (2H, m), 7,44 is 7.50 (2H, m), 7,87 (1H, d, J = 8.0 Hz), 8,49 (1H, d, J = 1.6 Hz), of 11.29 (1H, s).

2-((E)-2-Methyl-3-phenylacetamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,19 (3H, d, J = 1.2 Hz), 2,88-a 3.01 (4H, m), 7,05 (1H, DD, J = 8,1, 1.5 Hz), 7,16-7,21 (1H, m), 7.24 to to 7.32 (4H, m), 7,35-7,41 (1H, m), 7,43-7,53 (5H, m), 7,94 (1H, d, J = 8.1 Hz), 8,65 (1H, s), up 11,86 (1H, s).

Examples 440-446

Compounds shown in table 43, receive the same manner as in example 369.

Table 43

2-((E)-3-(4-Nitrophenyl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,77 (1H, DD, J = 8,8, 2,5 Hz), 7,12 (1H, d, J = 15.6 Hz), 7,14-7,21 (2H, m), 7,28 (1H, t, J = 7.5 Hz), 7,45-7,53 (2H, m), 7,71 (1H, d, J = 15.6 Hz), 8,00-8,08 (3H, m), compared to 8.26 (2H, d, J = 9.0 Hz), 8,35 (1H, d, J = the 2.6 Hz), 11,66 (1H, s), 13,40-13,65 (1H, usher.).

2-(3,5-Dichlorobenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.7 Hz), 7,16-7,22 (2H, m), 7,29 (1H, t, J = 7.4 Hz), 7,46-7,53 (2H, m), 7,88 (2H, d, J = 1,8 Hz), 7,94 (1H, t, J = 1,8 Hz), 8,07 (1H, d, J = 8,8 Hz), compared to 8.26 (1H, d, J = 2.7 Hz), 12,43 (1H, ).

2-(3,4-Dichlorobenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,9 and 2.5 Hz), 7,15-7,21 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,53 (2H, m), 7,84-a 7.92 (2H, m), 8,07 (1H, d, J = 8,9 Hz), of 8.09 (1H, d, J = 1.7 Hz), 8,30 (1H, d, J = 2.5 Hz), 12,43 (1H, s).

2-(3,5-Differentaite)-4-fenoxibenzamin acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.7 Hz), 7,15-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,46-to 7.64 (5H, m), 8,07 (1H, d, J = 8,8 Hz), of 8.28 (1H, d, J = 2.7 Hz), KZT 12.39 (1H, s).

2-(3,4-Differentaite)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: to 6.80 (1H, DD, J = 8,9 and 2.5 Hz), 7,15-7,22 (2H, m), 7,25-to 7.32 (1H, m), 7,45-7,53 (2H, m), 7,65-7,73 (1H, m), 7,75-of 7.82 (1H, m), 7,88-7,94 (1H, m), 8,07 (1H, d, J = 8,9 Hz), 8,30 (1H, d, J = 2.5 Hz), 12,37 (1H, ).

2-(3,5-Dimethylbenzamide)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,35 (6H, s)6,76 (1H, DD, J = 8,9, and 2.4 Hz), 7,16-7,22 (2H, m), 7,26-to 7.32 (2H, m), 7,45-EUR 7.57 (4H, m), of 8.06 (1H, d, J = 8,9 Hz), to 8.41 (1H, d, J = 2.4 Hz), 12,40 (1H, s).

2-((E)-2-Methyl-3-phenylacetamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,16 (3H, d, J = 1.5 Hz), to 6.75 (1H, DD, J = 8,8, and 2.6 Hz), 7,15-7,19 (2H, m), 7,25-7,31 (1H, m), 7,34-7,41 (1H, m), 7,42-7,52 (7H, m), with 8.05 (1H, d, J = 8,8 Hz), scored 8.38 (1H, d, J = 2.6 Hz), 12,06 (1H, s).

Examples 447-452

Compounds shown in table 44, receive the same manner as in example 345.

Table 44

2-(3,5-Dichlorobenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,47 (1H, TT, J = 7,3, 1,6 Hz), 7,51-to 7.59 (3H, m), 7,70 to 7.75 (2H, m), 7,94 (3H, s)to 8.12 (1H, d, J = 8,3 Hz), of 8.90 (1H, d, J = 1.7 Hz), 12,21 (1H, s).

2-(3,4-Dichlorobenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,44 is 7.50 (1H, m), 7,52-to 7.59 (3H, m), 7,70-7,76 (2H, m), 7,89-of 7.96 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 8,15-8,19 (1H, m), of 8.95 (1H, d, J = 1.7 Hz), 12,23 (1H, s).

2-(3,5-Differentaite)-4-phenylbenzene acid

1H-YAM who (DMSO-d 6) δ: 7,47 (1H, TT, J = 7,2, 1.5 Hz), 7,52-to 7.67 (6H, m), 7,70-to 7.77 (2H, m), 8,13 (1H, d, J = 8,3 Hz), 8,93 (1H, d, J = 1.7 Hz), 12,18 (1H, s).

2-(3,4-Differentaite)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,44 is 7.50 (1H, m), 7,52-7,58 (3H, m), to 7.67-to 7.77 (3H, m), 7,82-7,88 (1H, m), 7,94-8,02 (1H, m), 8,13 (1H, d, J = 8,3 Hz), 8,96 (1H, d, J = 1.7 Hz), 12,19 (1H, s).

2-(3,5-Dimethylbenzamide)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: of 2.38 (6H, s), 7,30 (1H, s), 7,44-7,58 (4H, m), 7,60 (2H, s), 7,70-7,76 (2H, m), 8,13 (1H, d, J = 8,3 Hz), the remaining 9.08 (1H, d, J = 1.7 Hz), of 12.26 (1H, s).

2-((E)-2-Methyl-3-phenylacetamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,22 (3H, d, J = 1.2 Hz), of 7.36-7,41 (1H, m), 7,44-7,58 (9H, m), 7,70-7,74 (2H, m)to 8.12 (1H, d, J = 8,3 Hz), the remaining 9.08 (1H, d, J = 1.7 Hz), 11,93 (1H, s).

Example 453

1.0 ml of methylene chloride, and 2.7 μl of N,N-dimethylformamide and 0,061 ml oxalicacid successively added to 0.11 g of 2-methoxybenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 57 mg of tert-butyl 2-amino-4-phenoxybenzoate in a mixture of 4.0 ml of methylene chloride and 0.45 ml of triethylamine, and the mixture is stirred at room temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chrome is cografya on silica gel [Flash Tube 2008, manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2-methoxybenzamido)-4-phenoxybenzoate.

10 ml triperoxonane acids are added to the obtained tert-butyl 2-(2-methoxybenzamido)-4-phenoxybenzoate and the mixture is stirred at room temperature for 3 minutes. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 52 mg of 2-(2-methoxybenzamido)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 3,99 (3H, s), 6,74 (1H, DD, J = 8,9, and 2.6 Hz), 7,06 for 7.12 (1H, m), 7,14-7,20 (2H, m), 7,21-7,29 (2H, m), 7,44-7,52 (2H, m), 7,55-of 7.60 (1H, m), to $ 7.91 (1H, DD, J = 7,8) and 1.7 Hz), of 8.04 (1H, d, J = 8,9 Hz), 8,55 (1H, d, J = 2,6 Hz), 12,40 (1H, s), 13,41 (1H, s).

Example 454

The following connection receive the same manner as in example 453.

2-(3-Methoxybenzamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: a-3.84 (3H, s), is 6.78 (1H, DD, J = 8,8, 2.4 Hz), 7,16-7,24 (3H, m), 7,29 (1H, t, J = 7,3 Hz), 7,43-of 7.55 (5H, m), 8,07 (1H, d, J = 8,8 Hz), 8,40 (1H, d, J = 2.4 Hz), 12,40 (1H, s), 13,65-13,85 (1H, usher.).

Example 455

5.0 ml of methylene chloride, 0,056 ml of triethylamine and 51 mg of 4-methoxybenzylamine successively added to 57 mg of tert-butyl 2-amino-4-phenoxybenzoate at room temperature, and the mixture was stirred at the same the temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(4-methoxybenzamido)-4-phenoxybenzoate.

10 ml triperoxonane acid is added to tert-butyl 2-(4-methoxybenzamido)-4-phenoxybenzoate, and the mixture is stirred at room temperature for 3 minutes. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 55 mg of 2-(4-methoxybenzamido)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 3.85 (3H, s), of 6.75 (1H, DD, J = 9,0, 2,5 Hz), 7,09-to 7.15 (2H, m), 7,15-7,21 (2H, m), 7,28 (1H, t, J = 7.4 Hz), 7,46-7,52 (2H, m), 7,86-to 7.93 (2H, m), of 8.06 (1H, d, J = 9.0 Hz), to 8.41 (1H, d, J = 2.5 Hz), of 12.33 (1H, C), 13,55-of 13.75 (1H, usher.).

Example 456

1.0 ml of methylene chloride, and 2.7 μl of N,N-dimethylformamide and 0,061 ml oxalicacid successively added to 0.11 g of 2-methoxybenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 54 mg of tert-butyl 2-amino-4-phenylbenzo the ATA in a mixture of 4.0 ml of methylene chloride and 0.45 ml of triethylamine, at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, and the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2-methoxybenzamido)-4-phenylbenzoate.

10 ml triperoxonane acids are added to the obtained tert-butyl 2-(2-methoxybenzamido)-4-phenylbenzoate, and the mixture is stirred at room temperature for 3 minutes. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining 65 mg of 2-(2-methoxybenzamido)-4-vinylbenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: a 4.03 (3H, s), 7,10-7,17 (1H, m), 7,26 (1H, d, J = 8,3 Hz), 7,43-to 7.64 (5H, m), 7,70-to 7.77 (2H, m), 8,02 (1H, DD, J = 7,8) and 1.7 Hz), 8,11 (1H, d, J = 8,3 Hz), 9,19 (1H, d, J = 1.7 Hz), 12,34 (1H, s)13,59 (1H, s).

Example 457

The following connection receive the same manner as in example 456.

2-(3-Methoxybenzamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 3,86 (3H, s), 7,22-7,26 (1H, m), 7,44-to 7.59 (7H, m), 7,72-to 7.77 (2H, m)to 8.14 (1H, d, J = 8.0 Hz), which is 9.09 (1H, d, J = 1.7 Hz), of 12.26 (1H, is), 13,80-14,00 (1H, usher.).

Examples 458, 459

Compounds shown in table 45, receive the same manner as in example 34.

Table 45

4-Phenethyl-2-(3-phenylpropanamide)benzoic acid

1H-NMR (DMSO-d6) δ: a 2.71 (2H, t, J = 7,7 Hz), 2,84-2,96 (4H, m)to 2.94 (2H, t, J = 7,7 Hz), 7,00 (1H, DD, J = 8,2, 1,6 Hz), 7,15-7,31 (10H, m), 7,87 (1H, d, J = 8,2 Hz), 8,43 (1H, d, J = 1.6 Hz), of 11.15 (1H, s), 13,45 (1H, s).

4-Phenethyl-2-(3,5-bis(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 2,90 totaling 3.04 (4H, m), 7,14 (1H, DD, J = 8,1) and 1.7 Hz), 7,15-7,21 (1H, m), 7.24 to to 7.32 (4H, m), of 7.96 (1H, d, J = 8.1 Hz), to 8.45 (1H, s), 8,49-charged 8.52 (1H, m), 8,54 (2H, s), 12,32 (1H, s), 13,70-13,90 (1H, usher.).

Example 460

The following connection receive the same manner as in example 282.

4-Phenyl-2-(3,5-bis(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 7,45-7,51 (1H, m), 7,52-to 7.61 (3H, m), 7,71-to 7.77 (2H, m), 8,13 (1H, d, J = 8.1 Hz), 8,46 (1H, s), 8,56 (2H, s), 8,91 (1H, d, J = 1.7 Hz), 12,38 (1H, s).

Example 461

The following connection receive the same manner as in example 321.

4 Phenoxy-2-(3,5-bis(trifluoromethyl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: at 6.84 (1H, DD, J = 8,9, and 2.6 Hz), 7,17-7,22 (2H, m), 7,27-7,33 (1H, m), 7,47-rate of 7.54 (2H, m), 8,08 (1H, d, J = 8,9 Hz), of 8.28 (1H, d, J = 2.6 Hz), 8,44 (1H, s), and 8.50 (2H, s), 12,63 (1H, s).

Example 462

The following connection get the same SP is way as in example 396.

2-((E)-3-(3-Nitrophenyl)acrylamide)-4-phenoxybenzoic acid

1H-NMR (DMCO-d6) δ: 6,76 (1H, DD, J = 8,9, 2.7 Hz), 7,12-7,22 (3H, m), 7,28 (1H, t, J = 7.4 Hz), 7,46-7,51 (2H, m), 7.68 per for 7.78 (2H, m), of 8.04 (1H, d, J = 8,9 Hz), 8,18-8,29 (2H, m), 8,35 (1H, d, J = 2.7 Hz), 8,61 (1H, s), of 11.61 (1H, C).

Example 463

5.0 ml of methylene chloride, 0,049 ml of triethylamine and 45 mg of 4-methoxybenzylamine successively added to 40 mg of methyl 2-amino-4-phenylbenzoate at room temperature and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving methyl-2-(4-methoxybenzamido)-4-phenylbenzoate.

To the obtained methyl 2-(4-methoxybenzamido)-4-phenylbenzoate add 1.0 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l and 3.0 ml of ethanol, and the mixture was stirred at 40°C for 2 hours. After cooling the reaction mixture to room temperature, add 8.0 ml of hydrochloric acid with a concentration of 0.38 mol/l and 10 ml of ethyl acetate. The organic layer is separated, dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced is the first pressure. The resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 55-100% acetonitrile/0.1% of triperoxonane acid], while receiving 6,1 mg of 2-(4-methoxybenzamido)-4-vinylbenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 3,86 (3H, s), to 7.15 (2H, d, J = 8,8 Hz), 7,44-EUR 7.57 (4H, m), 7,73 (2H, d, J = 7,4 Hz), 7,95 (2H, d, J = 8,8 Hz), 8,13 (1H, d, J = 8,3 Hz), which is 9.09 (1H, d, J = 1.4 Hz), 12,21 (1H, s), 13,70-13,90 (1H, usher.).

Example 464

2.0 ml of methylene chloride, and 2.7 μl of N,N-dimethylformamide and 0,061 ml oxalicacid successively added to of 0.13 g of 3-phenyl-1H-pyrazole-5-carboxylic acid at room temperature and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 60 mg of tert-butyl 2-amino-4-penicillinate in a mixture of 3.0 ml of methylene chloride and 0.45 ml of triethylamine at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-4-phenethyl-2-(3-phenyl-1H-pyrazole-5-carboxamido)benzoate.

1 ml triperoxonane acids are added to the obtained tert-butyl-4-phenethyl-2-(3-phenyl-1H-pyrazole-5-carboxamido)benzoate and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: ethyl acetate], while receiving 2.6 mg of 4-phenethyl-2-(3-phenyl-1H-pyrazole-5-carboxamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,89 totaling 3.04 (4H, m), 7,05 (1H, d, J = 7,7 Hz), 7,15-7,33 (6H, m), 7,38-7,44 (1H, m), 7,47-7,53 (2H, m), to 7.84 (2H, d, J = 7,6 Hz), 7,95 (1H, d, J = 7,7 Hz), a total of 8.74 (1H, s), KZT 12.39 (1H, s), 13,96 (1H, s).

Example 465

2.0 ml of methylene chloride, and 2.7 μl of N,N-dimethylformamide and 0,061 ml oxalicacid successively added to 0,13 g 2-acetoxybenzoic acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 60 mg of tert-butyl 2-amino-4-penicillinate in a mixture of 3.0 ml of methylene chloride and 0.45 ml of triethylamine at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution, the organic layer is separated, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate = 4:1], while receiving tert-butyl-2-(2-acetoxybenzoic)-4-venetianskt.

p> 10 ml triperoxonane acids are added to the obtained tert-butyl 2-(2-acetoxybenzoic)-4-penicillinate and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue successively added to 0.50 ml of methanol, and 0.50 ml of tetrahydrofuran and 10 mg of potassium carbonate and the mixture is stirred at room temperature for 3 hours. After removing insoluble substances by filtration add 3.0 ml of 10% aqueous citric acid solution and the solid is separated by filtration, while receiving 11 mg of 2-(2-hydroxybenzamide)-4-venetiancasino acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,88-to 3.02 (4H, m), 6,95-7,03 (2H, m), 7,07 (1H, DD, J = 8,1, 1,4 Hz), 7,15-7,21 (1H, m), 7.24 to to 7.32 (4H, m), 7,41-7,47 (1H, m), 7,87 (1H, DD, J = 7,9, and 1.6 Hz), 7,92 (1H, d, J = 8.1 Hz), 8,59 (1H, d, J = 1.4 Hz), 11,46 (1H, s), 12,22 (1H, s).

Example 466

10 mg of potassium carbonate are added to a solution containing 20 mg of 2-(4-acetoxybenzoic)-4-venetiancasino acid in a mixture of 1.0 ml of methanol and 1.0 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 3 hours. After removing insoluble substances by filtration add 3.0 ml of 10% aqueous citric acid solution, and the solid is separated by filtration, while receiving 15 mg of 2-(4-hydroxybenzamide)-4-finitive what sainoi acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,88-of 3.00 (4H, m), 6,93 (2H, d, J = 8.7 Hz),? 7.04 baby mortality (1H, DD, J = 8,1, 1,6 Hz), 7,15-7,21 (1H, m), 7.24 to to 7.32 (4H, m), 7,82 (2H, d, J = 8.7 Hz), 7,94 (1H, d, J = 8.1 Hz), 8,68 (1H, d, J = 1.6 Hz), 10,26 (1H, s), 12,09 (1H, s), 13,50-13,70 (1H, usher.).

Example 467

1.3 mg of 10% palladium on coal are added to a solution containing 10 mg of 4-phenoxy-2-((E)-4-phenyl-3-butanamide)benzoic acid in a mixture of 1.0 ml of methanol and 1.0 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 6 hours. After removing insoluble substances by filtration, the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining 4,6 mg 4 phenoxy-2-(4-phenylbutyramide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,83-of 1.94 (2H, m), 2,28 (2H, t, J = 7,6 Hz), 2,60 (2H, t, J = 7,7 Hz), of 6.49-to 6.57 (1H, m), 7,02 (2H, d, J = 7.8 Hz), 7,11-7,31 (6H, m), 7,35-the 7.43 (2H, m), 7,95 (1H, d, J = 8.6 Hz), 8,17 (1H, d, J = 2,4 Hz).

Example 468

1.0 mg of 10% palladium on coal are added to a solution containing 8.0 mg 4-phenethyl-2-((E)-4-phenyl-3-butanamide)benzoic acid in a mixture of 0.50 ml of methanol and 0.50 ml of ethyl acetate, and the mixture is stirred in hydrogen atmosphere at room temperature for 1 hour and 30 minutes. After removing insoluble substances by filtration plants is oritel is evaporated under reduced pressure, and the resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: ethyl acetate], while receiving 4,6 mg 4-phenethyl-2-(4-phenylbutyramide)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ (D2O): 1,86-2,02 (2H, m), 2,39 (2H, t, J = 7,3 Hz)of 2.64 (2H, t, J = 7,6 Hz), 2,85-2,96 (4H, m), 6,56 (1H, s), 7,01 (1H, d, J = 8,2 Hz), 7,14-7,34 (9H, m), 7,87 (1H, d, J = 8,2 Hz), 8,43 (1H, s).

Example 469

2.5 ml of methylene chloride, of 0.015 ml of N,N-dimethylformamide and 0,095 ml oxalicacid successively added to 0.17 g of 3-cyanobenzoic acid at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was added to a solution containing 0.25 g of tert-butyl 2-amino-4-phenylbenzoate in a mixture of 2.0 ml of methylene chloride and 0.35 ml of triethylamine at room temperature, and the mixture was stirred at the same temperature for 10 minutes. To the reaction mixture are added ethyl acetate, hydrochloric acid with a concentration of 1.0 mol/l tetrahydrofuran. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., e is UNT: chloroform], while receiving 0.29 grams of tert-butyl 2-(3-cyanobenzoyl)-4-phenylbenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: of 1.66 (9H, s), 7,37-7,44 (2H, m), 7,45-7,52 (2H, m), 7,66-7,74 (3H, m), 7,84-7,87 (1H, m), 8,10 (1H, d, J = 8,3 Hz), 8,28-8,31 (1H, m), of 8.37 (1H, t, J = 1.5 Hz), 9,19 (1H, d, J = 1.9 Hz), to 12.44 (1H, s).

Examples 470-476

Compounds shown in table 46, receive the same manner as in example 469.

Table 46

tert-Butyl-4-phenyl-2-(6-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoate

1H-NMR (CDCl3) δ: of 1.66 (9H, s)6,41 (2H, t, J = 2.3 Hz), 7,37 (1H, DD, J = 8,5, 2.0 Hz), 7,38-to 7.50 (4H, m), to 7.61 (2H, t, J = 2.3 Hz), 7,70-7,74 (2H, m), 8,10 (1H, d, J = 8.5 Hz), 8,43 (1H, DD, J = 8,8, 2,4 Hz)to 9.15 (1H, d, J = the 2.4 Hz), 9,23 (1H, d, J = 2.0 Hz), to 12.44 (1H, s).

tert-Butyl-4-phenyl-2-(2-(1H-pyrrol-1-yl)pyridine-4-carboxamido)benzoate

1H-NMR (CDCl3) δ: 1,68 (9H, s)6,40 (2H, t, J = 2.3 Hz), 7,38-7,52 (4H, m), of 7.64 (2H, t, J = 2.3 Hz), to 7.68 (1H, DD, J = 5,2, 1,4 Hz), 7,71 to 7.75 (2H, m), of 8.00 (1H, s)to 8.12 (1H, d, J = 8,3 Hz)8,64 (1H, d, J = 5,2 Hz), which 9.22 (1H, d, J = 2.0 Hz), 12,59 (1H, s).

tert-Butyl-4-phenyl-2-(3-(1H-pyrazole-1-yl)benzamido)benzoate

1H-NMR (CDCl3) δ: rate of 1.67 (9H, s), 6,51-6,53 (1H, m), 7,35-7,44 (2H, m), 7,45-7,51 (2H, m), 7,62-to 7.68 (1H, m), 7,70 for 7.78 (3H, m), 7,94-8,00 (1H, m), 8,04-to 8.12 (3H, m), at 8.36 is 8.38 (1H, m), a 9.25 (1H, d, J = 1.7 Hz), 12,42 (1H, s).

tert-Butyl 2-(biphenyl-4-carboxamido)-4-phenylbenzoate

1H-NMR (CDCl3) δ: rate of 1.67 (9H, s), of 7.36 (1H, DD, J = 8,4, 1.8 Hz), 7,37-7,44 (2H, m), 7,45-7,53 (4H, m), 7,65-of 7.70 (2H, m), 7,72-7,80 (4H, m), 8,10 (1H, d, J = 8,4 Hz), 8,14-8,18 (2H, m), 9.28 are (1H, d, J = 1,8 Hz), 2,33 (1H, C).

tert-Butyl 2-(3-acetylbenzoic)-4-phenylbenzoate

1H-NMR (CDCl3) δ: of 1.66 (9H, s), of 2.72 (3H, s), of 7.36-7,44 (2H, m), 7,45-7,51 (2H, m), to 7.67 (1H, t, J = 7.8 Hz), 7,70-7,76 (2H, m), 8,11 (1H, d, J = 8,3 Hz), 8,16 is 8.22 (1H, m), 8,25-8,30 (1H, m), 8,68-8,72 (1H, m), a 9.25 (1H, d, J = 1.9 Hz), 12,49 (1H, s).

tert-Butyl-4-phenyl-2-(3-(1H-tetrazol-1-yl)benzamido)benzoate

1H-NMR (CDCl3) δ: rate of 1.67 (9H, s), 7,38 was 7.45 (2H, m), 7,46-7,53 (2H, m), 7,70 to 7.75 (2H, m), 7,81 (1H, t, J = 7.9 Hz), 8,03-8,07 (1H, m)to 8.12 (1H, d, J = 8,3 Hz), 8,21-8,24 (1H, m), 8,42 (1H, t, J = 1,8 Hz), 9,13 (1H, s), which 9.22 (1H, d, J = 1.7 Hz), 12,57 (1H, s).

tert-Butyl 2-(3-(3,5-dimethyl-1H-pyrazole-1-yl)benzamido)-4-phenylbenzoate

1H-NMR (CDCl3) δ: 1,65 (9H, s), 2,32 (3H, s)to 2.46 (3H, s), equal to 6.05 (1H, s), of 7.36 (1H, DD, J = 8,3, 1.9 Hz), of 7.36-the 7.43 (1H, m), 7,44 is 7.50 (2H, m), of 7.64 (1H, t, J = 7.9 Hz), 7,70-7,74 (2H, m), 7,74-7,79 (1H, m), 8,02-8,07 (1H, m,), of 8.09 (1H, d, J = 8,3 Hz)to 8.12 (1H, t, J = 1.7 Hz), the 9.25 (1H, d, J = 1.7 Hz), 12,40 (1H, s).

Example 477

To 0.17 g of 3-cyanobenzoic acid are successively added to 2.5 ml of methylene chloride, of 0.015 ml of N,N-dimethylformamide and 0,095 ml oxalicacid at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was added to a solution of 0.26 g of tert-butyl 2-amino-4-phenoxybenzoate in a mixture of 2.0 ml of methylene chloride and 0.35 ml of triethylamine at room temperature, and the mixture was stirred at the same temperature for 10 minutes. To the reaction mixture are added ethyl acetate, hydrochloric acid with concentric is it 1.0 mol/l tetrahydrofuran. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: chloroform], while receiving 0.20 g of tert-butyl 2-(3-cyanobenzoyl)-4-phenoxybenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: 1,63 (9H, s)6,70 (1H, DD, J = 8,9, 2.7 Hz), 7,08-7,13 (2H, m), 7.18 in-7,24 (1H, m), 7,38 was 7.45 (2H, m), 7,62-to 7.68 (1H, m), 7,83 (1H, dt, J = 7,6, 1.5 Hz), 8,00 (1H, d, J = 8,9 Hz), 8,21 compared to 8.26 (1H, m), 8,31 (1H, t, J = 1.5 Hz), 8,53 (1H, d, J = 2.7 Hz), 12,48 (1H, s).

Examples 478-484

Compounds shown in table 47, receive the same manner as in example 477.

Table 47

tert-Butyl-4-phenoxy-2-(6-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoate

1H-NMR (CDCl3) δ: 1,63 (9H, s)6,40 (2H, t, J = 2.3 Hz), 6,69 (1H, DD, J = 8,9 and 2.5 Hz), 7,08-7,14 (2H, m), 7.18 in-7,24 (1H, m), 7,38 was 7.45 (3H, m), to 7.59 (2H, t, J = 2.3 Hz), 8,00 (1H, d, J = 8,9 Hz), of 8.37 (1H, DD, J = 8,8, 2,4 Hz), 8,56 (1H, d, J = 2.5 Hz), which is 9.09 (1H, d, J = 2.4 Hz), 12,48 (1H, s).

tert-Butyl-4-phenoxy-2-(2-(1H-pyrrol-1-yl)pyridine-4-carboxamido)benzoate

1H-NMR (CDCl3) δ: 1,64 (9H, s), to 6.39 (2H, t, J = 2.2 Hz), 6,72 (1H, DD, J = 8,9 and 2.5 Hz), 7,08-7,14 (2H, m), 7.18 in-to 7.25 (1H, m), 7,38-7,46 (2H, m), 7,60-to 7.64 (3H, m), to 7.93 (1H, s), 8,01 (1H, d, J = 8,8 Hz), 8,54 (1H, d, J = 2,5 Hz), at 8.60 (1H, d, J = 5,1 Hz), br12.62 (1H, s).

tert-Butyl-4-phenoxy-2-(2-(1H-shall Errol-1-yl)pyridine-3-carboxamido)benzoate

1H-NMR (CDCl3) δ: for 1.49 (9H, s), from 6.22 (2H, t, J = 2.3 Hz), 6,63 (1H, DD, J = 8,9 and 2.5 Hz), 7,06-7,14 (2H, m), 7,16-7,24 (3H, m), 7,30 (1H, DD, J = 7,7, a 4.9 Hz), 7,37-7,44 (2H, m), 7,88 (1H, d, J = 8,9 Hz), with 8.05 (1H, DD, J = 7,7, 1,8 Hz), 8,51 (1H, d, J = 2.5 Hz), 8,59 (1H, DD, J = 4,9, 1.8 Hz), are 11.62 (1H, s).

tert-Butyl-4-phenoxy-2-(3-(1H-pyrazole-1-yl)benzamido)benzoate

1H-NMR (CDCl3) δ: 1,63 (9H, s), 6,51 (1H, t, J = 2.1 Hz), 6,69 (1H, DD, J = 8,9, and 2.4 Hz), 7,09-7,14 (2H, m), 7,21 (1H, t, J = 7,3 Hz), 7,38-7,44 (2H, m), to 7.61 (1H, t, J = 7.9 Hz), of 7.75 (1H, d, J = 1.5 Hz), 7,88-a 7.92 (1H, m), 8,00 (1H, d, J = 8,9 Hz), 8,02-8,07 (2H, m), 8,28-8,31 (1H, m), 8,58 (1H, d, J = 2.4 Hz), 12,45 (1H, s).

tert-Butyl 2-(biphenyl-4-carboxamido)-4-phenoxybenzoate

1H-NMR (CDCl3) δ: 1,63 (9H, s), to 6.67 (1H, DD, J = 8,9 and 2.5 Hz), 7,08-7,14 (2H, m), 7,16-of 7.23 (1H, m), of 7.36-7,52 (5H, m), 7,63-to 7.68 (2H, m), 7,72 for 7.78 (2H, m), to 7.99 (1H, d, J = 8,9 Hz), 8.07-a 8,13 (2H, m), to 8.62 (1H, d, J = 2,5 Hz), 12,37 (1H, s).

tert-Butyl 2-(3-acetylbenzoic)-4-phenoxybenzoate

1H-NMR (CDCl3) δ: 1,63 (9H, s), 2,70 (3H, s), 6,69 (1H, DD, J = 9,0, 2.7 Hz), 7,10-to 7.15 (2H, m), 7.18 in-of 7.23 (1H, m), 7,38 was 7.45 (2H, m), 7,63 (1H, t, J = 7.8 Hz), 8,00 (1H, d, J = 9.0 Hz), 8,14-8,19 (1H, m), 8,20-8,24 (1H, m), to 8.57 (1H, d, J = 2.7 Hz), 8,62-8,64 (1H, m), to 12.52 (1H, s).

tert-Butyl 2-(3-(3,5-dimethyl-1H-pyrazole-1-yl)benzamido)-4-phenoxybenzoate

1H-NMR (CDCl3) δ: of 1.61 (9H, s), 2,31 (3H, s), is 2.44 (3H, s), 6,03 (1H, s), to 6.67 (1H, DD, J = 8,9 and 2.5 Hz), 7,08-7,13 (2H, m), 7,16-7,22 (1H, m), 7,37-the 7.43 (2H, m), 7,60 (1H, t, J = 7.9 Hz), 7,72-7,76 (1H, m), of 7.96 shed 8.01 (2H, m,), of 8.06 (1H, t, J = 1,8 Hz), 8,59 (1H, d, J = 2.5 Hz), 12,43 (1H, s).

Example 485

of 0.015 ml of N,N-dimethylformamide are added to a solution of 47 m is 6-(1H-pyrrol-1-yl)pyridine-3-carboxylic acid in a mixture of 2.0 ml of methylene chloride and 0.024 ml of oxalicacid, and the mixture is stirred at room temperature for 30 minutes. To the reaction mixture at room temperature successively added 74 mg of tert-butyl 2-amino-4-penicillinate and 0,090 ml of triethylamine, and the mixture was stirred at the same temperature for 1 hour and 40 minutes. To the reaction mixture of hydrochloric acid with a concentration of 1.0 mol/l and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: chloroform], while receiving 62 mg of tert-butyl-4-phenethyl-2-(6-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoate as a white solid.

1H-NMR (CDCl3) δ: 1,63 (9H, s), 2,90-is 3.08 (4H, m), 6,41 (2H, t, J = 2.3 Hz), make 6.90 (1H, DD, J = 8,1) and 1.7 Hz), 7,17-to 7.32 (5H, m), 7,46 (1H, d, J = 8.7 Hz), 7,60 (2H, d, J = 2.3 Hz), to 7.93 (1H, d, J = 8.1 Hz), to 8.41 (1H, DD, J = 8,7, 2.3 Hz), 8,83 (1H, d, J = 1.7 Hz), 9,13 (1H, d, J = 2.3 Hz), 12,40 (1H, s).

Examples 486-488

Compounds shown in table 48, receive the same manner as in example 485.

Table 48

tert-Butyl-4-phenethyl-2-(2-(1H-pyrrol-1-yl)pyridine-4-carboxamido)benzoate

1H-NMR (CDCl3) δ: 1,64 (9H, s), 2,94 was 3.05 (4H, m), 6,40 (2H, t, J = 2.3 Hz), 6,94 (1H, DD, J =8,2, the 1.7 Hz), 7.18 in-7,33 (5H, m), 7,63 (2H, t, J = 2.3 Hz), 7,66 (1H, DD, J = 5,1, 1.5 Hz), 7,94 (1H, d, J = 8,2 Hz), 7,97-to 7.99 (1H, m), 8,63 (1H, d, J = 5,1 Hz), 8,81 (1H, d, J = 1.7 Hz), 12,55 (1H, s).

tert-Butyl 2-(biphenyl-3-carboxamido)-4-venetianskt

1H-NMR (CDCl3) δ: 1,64 (9H, s), 2,94-of 3.06 (4H, m), 6.89 in (1H, DD, J = 8,2, 1,6 Hz), 7,16-7,34 (5H, m), 7,35-the 7.43 (1H, m), 7,45-7,52 (2H, m), to 7.61 (1H, t, J = 7,7 Hz), 7,70 to 7.75 (2H, m), 7,78-to 7.84 (1H, m), to 7.93 (1H, d, J = 8,2 Hz), 8,80-with 8.05 (1H, m), at 8.36 (1H, t, J = 1.7 Hz), 8,88 (1H, d, J = 1.6 Hz), 12,38 (1H, s).

tert-Butyl 2-(biphenyl-4-carboxamido)-4-venetianskt

1H-NMR (CDCl3) δ: 1,64 (9H, s), 2,92-of 3.06 (4H, m), 6.89 in (1H, DD, J = 8,1, 1,6 Hz), 7,16-7,34 (5H, m), 7,37-7,44 (1H, m), 7,45-7,53 (2H, m), of 7.64-of 7.70 (2H, m), 7,74-7,80 (2H, m), to 7.93 (1H, d, J = 8.1 Hz), 8,12-8,17 (2H, m), 8,89 (1H, d, J = 1.6 Hz), 12,30 (1H, s).

Example 489

of 0.015 ml of N,N-dimethylformamide are added to a solution containing 47 mg of 4-(1H-pyrrol-1-yl)benzoic acid in a mixture of 2.0 ml of methylene chloride and 0.024 ml of oxalicacid, and the mixture is stirred at room temperature for 30 minutes. To the reaction mixture at room temperature successively added 67 mg of tert-butyl 2-amino-4-phenylbenzoate and 0,090 ml of triethylamine, and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, rastvoritel is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: chloroform], while receiving 64 mg of tert-butyl 4-phenyl-2-(4-(1H-pyrrol-1-yl)benzamido)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 1.66 (9H, s)6,40 (2H, t, J = 2.2 Hz), 7,20 (2H, t, J = 2.2 Hz), 7,35 (1H, DD, J = 8,3, 1.8 Hz), 7,37-the 7.43 (1H, m), 7,44 is 7.50 (2H, m), 7,54-to 7.59 (2H, m), 7,71-7,76 (2H, m), 8,10 (1H, d, J = 8,3 Hz), 8,14-8,18 (2H, m), 9,26 (1H, d, J = 1,8 Hz), of 12.33 (1H, s).

Example 490

The following connection receive the same manner as in example 489.

tert-Butyl 2-(biphenyl-2-carboxamido)-4-phenylbenzoate

1H-NMR (CDCl3) δ: of 1.52 (9H, s), 7,20-7,40 (5H, m), 7,40-7,58 (7H, m), of 7.64-of 7.70 (2H, m), 7,74 for 7.78 (1H, m), to 7.93 (1H, d, J = 8,3 Hz), 9,10 (1H, s)of 11.26 (1H, s).

Example 491

of 0.015 ml of N,N-dimethylformamide are added to a solution containing 47 mg of 3-(1H-pyrrol-1-yl)benzoic acid in a mixture of 2.0 ml of methylene chloride and 0.024 ml of oxalicacid, and the mixture is stirred at room temperature for 30 minutes. To the reaction mixture at room temperature successively added 71 mg of tert-butyl 2-amino-4-phenoxybenzoate and 0,090 ml of triethylamine and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and the shat over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 40:1], while receiving 31 mg of tert-butyl-4-phenoxy-2-(3-(1H-pyrrol-1-yl)benzamido)benzoate as a white solid.

1H-NMR (CDCl3) δ: 1,63 (9H, s)6,38 (2H, t, J = 2.2 Hz), of 6.68 (1H, DD, J = 8,9 and 2.5 Hz), 7,09-7,14 (2H, m), 7,17-7,24 (3H, m), 7,37-7,44 (2H, m), 7,55-of 7.60 (2H, m), 7,84-7,88 (1H, m), of 8.00 (1H, d, J = 8,9 Hz), 8,09-8,11 (1H, m,), 8,58 (1H, d, J = 2.5 Hz), 12,46 (1H, s).

Example 492

The following connection receive the same manner as in example 491.

tert-Butyl 2-(biphenyl-2-carboxamido)-4-phenoxybenzoate

1H-NMR (CDCl3) δ: to 1.48 (9H, s), is 6.54 (1H, DD, J = 9,0, 2.6 Hz), 7,02-was 7.08 (2H, m), 7,16 (1H, t, J = 7.4 Hz), 7,21-7,40 (5H, m), 7,41-7,56 (5H, m), 7,69-7,73 (1H, m), 7,81 (1H, d, J = 9.0 Hz), of 8.47-charged 8.52 (1H, usher.), 11,23-11,27 (1H, usher.).

Example 493

to 4.0 ml of methylene chloride, of 0.015 ml of N,N-dimethylformamide and 0,050 ml oxalicacid successively added to 99 mg 3 biphenylcarbonic acid at room temperature, and the mixture was stirred at the same temperature for 20 minutes. To the reaction mixture at room temperature successively added 0.16 ml of triethylamine and 0.12 g of tert-butyl 2-amino-4-phenylbenzoate, and the mixture was stirred at the same temperature for 10 minutes. To the reaction is Oh mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: chloroform], while receiving 0.14 g of tert-butyl 2-(biphenyl-3-carboxamido)-4-phenylbenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: rate of 1.67 (9H, s), 7,34-the 7.43 (3H, m), 7,45-7,51 (4H, m), a 7.62 (1H, t, J = 7,7 Hz), 7,70-7,76 (4H, m), 7,82 (1H, DDD, J = 7,7, of 1.8, 1.0 Hz), of 8.04 (1H, DDD, J = 7,8, and 1.8, 1.0 Hz), 8,10 (1H, d, J = 8,3 Hz), of 8.37-to 8.40 (1H, m,), 9.28 are (1H, d, J = 1.7 Hz), 12,42 (1H, s).

Example 494

to 4.0 ml of methylene chloride, of 0.015 ml of N,N-dimethylformamide and 0,050 ml oxalicacid successively added to 99 mg 3 biphenylcarbonic acid at room temperature, and the mixture was stirred at the same temperature for 20 minutes. To the reaction mixture at room temperature successively added 0.16 ml of triethylamine and 0.13 g of tert-butyl 2-amino-4-phenoxybenzoate, and the mixture was stirred at the same temperature for 10 minutes. To the reaction mixture are added ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and actuarial is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: chloroform], while receiving 0.14 g of tert-butyl 2-(biphenyl-3-carboxamido)-4-phenoxybenzoate in the form of a white solid.

1H-NMR (CDCl3) δ: 1,63 (9H, s), of 6.68 (1H, DD, J = 8,9 and 2.5 Hz), 7,08-to 7.15 (2H, m), 7,16-7,22 (1H, m), 7,35-7,52 (5H, m), 7,58 (1H, t, J = 7,7 Hz), 7.68 per-7,74 (2H, m), to 7.77-of 7.82 (1H, m), 7,95-of 8.04 (2H, m), 8.30 to-8,32 (1H, m), 8,61 (1H, d, J = 2.5 Hz), 12,46 (1H, s).

Example 495

0.25 ml of acetic acid and 4.1 μl of 2.5-dimethoxytetrahydrofuran successively added to 10 mg of 2-(4-aminobenzamide)-4-phenoxybenzoic acid at room temperature, and the mixture was stirred at 90°C for 5 minutes. After cooling the reaction mixture to room temperature, add ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: ethyl acetate], while receiving 3.8 mg 4 phenoxy-2-(4-(1H-pyrrol-1-yl)benzamido)benzoic acid as a brown solid.

1H-NMR (DMSO-d6) δ: 6,33 (2H, t, J = 2.2 Hz), 6,78 (1H, DD, J = 8,, the 2.6 Hz), 7,16-7,21 (2H, m), 7,28 (1H, t, J = 7.4 Hz), 7,46-7,53 (2H, m), 7,53 (2H, t, J = 2.2 Hz), 7,80-a 7.85 (2H, m), of 7.96 shed 8.01 (2H, m), 8,08 (1H, d, J = 8,8 Hz), to 8.41 (1H, d, J = 2.6 Hz), 12,49 (1H, s).

Example 496

1.0 ml of methylene chloride, 0,010 ml of N,N-dimethylformamide and 0,064 ml oxalicacid successively added to 0,13 g of 3,4-dimethoxyphenol acid at room temperature, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was added to a solution containing 0.15 g of tert-butyl 2-amino-4-penicillinate in a mixture of 1.5 ml of methylene chloride and 0.14 ml of triethylamine under ice cooling, and the mixture is stirred at room temperature over night. The solvent is evaporated under reduced pressure, and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 4:1], while receiving 0.12 g of tert-butyl 2-((E)-3-(3,4-acid)acrylamide)-4-penicillinate in the form of a white solid.

1H-I Is R (CDCl 3) δ: 1,63 (9H, s), 2,94-a 3.01 (4H, m), 3,93 (3H, s), of 3.97 (3H, s), 6,51 (1H, d, J = 15,5 Hz)6,86 (1H, DD, J = 8,3, 1.3 Hz), 6.89 in (1H, d, J = 8,3 Hz), 7,13 (1H, d, J = 1.7 Hz), 7,16-to 7.32 (6H, m), 7,71 (1H, d, J = 15,5 Hz), 7,89 (1H, d, J = 8,3 Hz), 8,82 (1H, d, J = 1.3 Hz), of 11.45 (1H, s).

Example 497

1.5 ml of methylene chloride, 0,010 ml of N,N-dimethylformamide and 0,062 ml oxalicacid successively added to 0,13 g of 6-(piperidine-1-yl)pyridine-3-carboxylic acid at room temperature and the mixture was stirred at the same temperature for 1 hour and 30 minutes. The solvent is evaporated under reduced pressure, add 1.5 ml of methylene chloride and, while cooling with ice, the mixture was added to a solution containing 0.15 g of tert-butyl 2-amino-4-penicillinate in a mixture of 1.5 ml of methylene chloride and 0.14 ml of triethylamine, and the mixture is stirred at room temperature over night. The solvent is evaporated under reduced pressure, and add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after sequential washing with a saturated aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration, thus obtaining 0.17 g of tert-butyl-4-phenethyl-2-(6-(piperidine-1-espiridion-3-carboxamido)benzoate as a white solid.

1H-NMR (CDCl3) δ: 1,52-to 1.77 (6H, m)to 1.61 (9H, s), of 2.97 (4H, s), 3,66-to 3.73 (4H, m)6,70 (1H, d, J = 9,2 Hz), at 6.84 (1H, DD, J = 8,2) and 1.7 Hz), 7,17-7,31 (5H, m), of 7.90 (1H, d, J = 8,2 Hz), 8,10 (1H, DD, J = 9,2, 2.7 Hz), 8,86 (1H, d, J = 1.7 Hz), 8,89 (1H, d, J = 2.7 Hz), 12,11 (1H, s).

Example 498

0.5 ml triperoxonane acid are added to a solution containing 10 mg of tert-butyl 2-(3-cyanobenzoyl)-4-phenoxybenzoate in 0.5 ml of methylene chloride, and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether and the solid is separated by filtration, while receiving 5.0 mg of 2-(3-cyanobenzoyl)-4-phenoxybenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,9, and 2.6 Hz), 7,16-7,20 (2H, m), 7,29 (1H, t, J = 7.2 Hz), 7,47-7,52 (2H, m), 7,81 (1H, t, J = 7.8 Hz), 8,08 (1H, d, J = 8,9 Hz)to 8.12 (1H, d, J = 7.8 Hz), to 8.20 (1H, d, J = 8.0 Hz), 8,29 (1H, ), 8,31 (1H, d, J = 2.6 Hz), 12,48 (1H, s).

Examples 499-507

Compounds shown in table 49, receive the same manner as in example 498.

Table 49

4 Phenoxy-2-(6-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,37 (2H, t, J = 2.3 Hz), for 6.81 (1H, DD, J = 8,9, and 2.6 Hz), 7,16-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,46-rate of 7.54 (2H, m), 7,78 (2H, t, J = 2.3 Hz), 7,92 (1H, d, J = 8,8 Hz), of 8.09 (1H, d, J = 9.0 Hz), 8,30-at 8.36 (2H, m), of 8.92 (1H, d, J = 2.4 Hz), 12,40 (1H, s).

4 Phenoxy-2-(2-(1H-feast of the ol-1-yl)pyridine-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6.35mm (2H, t, J = 2.3 Hz), 6,85 (1H, DD, J = 8,9, 2.7 Hz), 7,16-7,24 (2H, m), 7,26-7,34 (1H, m), 7,46-rate of 7.54 (2H, m), to 7.61 (1H, DD, J = 5,1, 1.2 Hz), 7,74 (2H, t, J = 2.3 Hz), with 8.05 (1H, s), 8,10 (1H, d, J = 8,9 Hz), 8,32 (1H, d, J = 2.7 Hz), 8,66 (1H, d, J = 5,1 Hz), 12,50 (1H, s).

4 Phenoxy-2-(2-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,21 (2H, t, J = 2.2 Hz), to 6.75 (1H, DD, J = 8,9, 2.7 Hz), 7,16-7,22 (4H, m), 7,25-7,30 (1H, m), 7,46-rate of 7.54 (3H, m), 7,98 (1H, d, J = 8,9 Hz), 8,15 is 8.22 (2H, m)8,64 (1H, DD, J = 4,9) and 1.7 Hz), 11,67 (1H, s).

4 Phenoxy-2-(3-(1H-pyrazole-1-yl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,60 (1H, DD, J = 2,6, 1.8 Hz), to 6.80 (1H, DD, J = 8,9, and 2.6 Hz), 7,16-of 7.23 (2H, m), 7,27-to 7.32 (1H, m), 7,46-of 7.55 (2H, m), 7,71 (1H, t, J = 7.9 Hz), 7,80-7,86 (2H, m), 8.07-a 8,13 (2H, m), to 8.41-8,42 (2H, m), 8,61 (1H, d, J = 2.4 Hz), of 12.53 (1H, s).

2-(Biphenyl-3-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,8, 2.7 Hz), 7,17-7,22 (2H, m), 7,26-7,33 (1H, m), the 7.43 (1H, TT, J = 7,4, 1.5 Hz), 7,46-of 7.55 (4H, m), 7,68 (1H, t, J = 7.8 Hz), 7,72-to 7.77 (2H, m), of 7.90-of 7.97 (2H, m), 8,08 (1H, d, J = 8,8 Hz), 8,19 (1H, t, J = 1.7 Hz), 8,43 (1H, d, J = 2.7 Hz), 12,54 (1H, s).

2-(Biphenyl-4-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,9 and 2.5 Hz), 7,16-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,41-of 7.55 (5H, m), 7,75-7,80 (2H, m), 7,87-to 7.93 (2H, m), 7,98-of 8.04 (2H, m), of 8.09 (1H, d, J = 8,9 Hz), 8,43 (1H, d, J = 2.5 Hz), 12,48 (1H, ).

2-(3-Acetylbenzoic)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,66 (3H, s), to 6.80 (1H, DD, J = 8,9, and 2.6 Hz), 7,16-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,46-rate of 7.54 (2H, m), of 7.75 (1H, t, J = 7.8 Hz), of 8.09 (1H, d,J = 8,9 Hz), 8,15-8,19 (1H, m), 8,20-8,24 (1H, m), 8,40 (1H, d, J = 2.6 Hz), 8,48-8,51 (1H, m), 12,58 (1H, s), 13,60-14,00 (1H, usher.).

2-(3-(3,5-Dimethyl-1H-pyrazole-1-yl)benzamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 2,20 (3H, s), is 2.37 (3H, s), 6,13 (1H, s), 6,79 (1H, DD, J = 8,9 and 2.5 Hz), 7,17-7,21 (2H, m), 7,26-to 7.32 (1H, m), 7,46-7,53 (2H, m), of 7.70 (1H, t, J = 7.8 Hz), 7,76-7,81 (1H, m), 7,88-to 7.93 (1H, m), to 7.99 (1H, t, J = 2.0 Hz), 8,08 (1H, d, J = 8,9 Hz), 8,40 (1H, d, J = 2.5 Hz), 12,46 (1H, s), 13,50-14,00 (1H, usher.).

2-(Biphenyl-2-carboxamido)-4-phenoxybenzoic acid

1H-NMR (DMSO-d6) δ: 6,66 (1H, DD, J = 8,8, 2.4 Hz), 7,11-7,16 (2H, m), 7,22-the 7.43 (6H, m), 7,44-of 7.55 (4H, m), a 7.62 (1H, TD, J = 7,6, 1.5 Hz), to 7.67 (1H, DD, J = 7,6, 1.2 Hz), to $ 7.91 (1H, d, J = 8,8 Hz), by 8.22 (1H, s), 11,44 (1H, s), 13,30-13,60 (1H, usher.).

Example 508

0.5 ml triperoxonane acid are added to a solution containing 10 mg of tert-butyl 2-(3-cyanobenzoyl)-4-phenylbenzoate in 0.5 ml of methylene chloride, and the mixture is stirred at room temperature for 1 hour and 30 minutes. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining a 7.6 mg of 2-(3-cyanobenzoyl)-4-vinylbenzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 7,44 is 7.50 (1H, m), 7,52-of 7.60 (3H, m), 7,72-to 7.77 (2H, m), to 7.84 (1H, t, J = 7.9 Hz), 8,12-8,18 (2H, m), 8,25-8,30 (1H, m), 8,35 is 8.38 (1H, m), of 8.95 (1H, d, J = 1.7 Hz), 12,24 (1H, s).

Examples 509-516

Compounds shown in table 50, receive the same manner as in example 508.

Table 50

4-Phenyl-2-(6-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,38 (2H, t, J = 2.1 Hz), 7,44 is 7.50 (1H, m), 7,52-7,58 (3H, m), 7,71-7,76 (2H, m), 7,80 (2H, t, J = 2.1 Hz), of 7.96 (1H, d, J = 8.6 Hz), 8,15 (1H, d, J = 8,3 Hz), 8,40 (1H, DD, J = 8,6, 2.4 Hz), 8,98-of 9.02 (2H, m), 12,25 (1H, s).

4-Phenyl-2-(2-(1H-pyrrol-1-yl)pyridine-4-carboxamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,37 (2H, t, J = 2.3 Hz), of 7.48 (1H, TT, J = 7,3, 1,6 Hz), 7,53 to 7.62 (3H, m), of 7.69 (1H, DD, J = 5,1, 1,4 Hz), 7,74 for 7.78 (4H, m), 8,13 (1H, s), 8,16 (1H, d, J = 8,3 Hz), 8,69 (1H, DD, J = 5,1, 0.8 Hz), 8,98 (1H, d, J = 1.7 Hz), 12,29 (1H, s).

4-Phenyl-2-(3-(1H-pyrazole-1-yl)benzamido)benzoic acid

1H-NMR (DMSO-d6) δ: 6,62 (1H, DD, J = 2,4, 2.0 Hz), 7,45-7,51 (1H, m), 7,53-of 7.60 (3H, m), 7,72 for 7.78 (3H, m), 7,82-to 7.84 (1H, m), 7,88-7,94 (1H, m), 8,10-8,17 (2H, m), 8,49 (1H, t, J = 1,8 Hz), 8,63 (1H, d, J = 2.4 Hz), which is 9.09 (1H, d, J = 1.7 Hz), 12,38 (1H, s).

2-(Biphenyl-3-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,42-of 7.60 (7H, m), 7,69-7,80 (5H, m), 7,94-8,02 (2H, m), 8,15 (1H, d, J = 8,3 Hz), compared to 8.26 (1H, s), 9,11 (1H, d, J = 1.7 Hz), 12,40 (1H, s).

2-(Biphenyl-4-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,42-of 7.60 (7H, m), 7,74-of 7.82 (4H, m), of 7.90-of 7.95 (2H, m), 8,06-8,11 (2H, m), 8,16 (1H, d, J = 8,3 Hz), 9,11 (1H, d, J = 1.7 Hz), 12,34 (1H, s).

2-(3-Acetylbenzoic)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 2,69 (3H, s), 7,45 is 7.50 (1H, m), 7,52-to 7.59 (3H, m), 7,72-of 7.82 (3H, m), 8,15 (1H, d, J = 8,3 Hz), 8,24 (2H, DD, J = 7,8) and 1.7 Hz), to 8.57 (1H, t, J = 1.7 Hz), 9,07 (1H, d, J 2.0 Hz), 12,41 (1H, s).

2-(3-(3,5-Dimethyl-1H-pyrazole-1-yl)benzamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: of 2.21 (3H, s), 2,39 (3H, d, J = 0.5 Hz), 6,14 (1H, s), 7,47 (1H, TT, J = 7,3, 1.5 Hz), 7,52-7,58 (3H, m), 7,70-to 7.77 (3H, m), 7,79-of 7.82 (1H, m), of 7.96-to 7.99 (1H, m), 8,06-8,07 (1H, m)to 8.14 (1H, d, J = 8,3 Hz), 9,05-9,07 (1H, m), 12,30 (1H, s).

2-(Biphenyl-2-carboxamido)-4-phenylbenzene acid

1H-NMR (DMSO-d6) δ: 7,29 (1H, TT, J = 7,2, 1.7 Hz), 7,34-of 7.48 (6H, m), of 7.48-to 7.59 (4H, m), to 7.61-of 7.70 (3H, m), 7,73 (1H, DD, J = 7,6, 1.2 Hz), to 7.99 (1H, d, J = 8,3 Hz), cent to 8.85 (1H, s), 11,35 (1H, s), 13,40-13,80 (1H, usher.).

Example 517

1.0 ml triperoxonane acid are added to a solution containing 20 mg of tert-butyl-4-phenethyl-2-(6-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoate in 1.0 ml of methylene chloride, and the mixture is stirred at room temperature for 1 hour and 30 minutes. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, while receiving 17 mg of 4-phenethyl-2-(6-(1H-pyrrol-1-yl)pyridine-3-carboxamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,90-to 3.02 (4H, m), 6,38 (2H, t, J = 2.3 Hz), 7,11 (1H, DD, J = 8,3, 1,6 Hz), 7,15-7,24 (1H, m), 7,25-to 7.32 (4H, m), 7,79 (2H, t, J = 2.3 Hz), 7,94 (1H, d, J = 8.7 Hz), of 7.97 (1H, d, J = 8,3 Hz), of 8.37 (1H, DD, J = of 8.7, 2.3 Hz), 8,58-8,61 (1H, m), 8,97 (1H, d, J = 2.3 Hz), 12,15 (1H, s), 13,60-13,80 (1H, usher.).

Examples 518-521

Compounds shown in table 51, still get the same way as in the example 517.

Table 51

4-Phenethyl-2-(2-(1H-pyrrol-1-yl)pyridine-4-carboxamido)benzoic acid

1H-NMR (DMSO) δ: 2,90 totaling 3.04 (4H, m), 6,37 (2H, t, J = 2.3 Hz), 7,12-7,22 (2H, m), 7,25-to 7.32 (4H, m), 7,66 (1H, DD, J = 5,1, 1.5 Hz), 7,74 (2H, t, J = 2.3 Hz), of 7.97 (1H, d, J = 8,3 Hz), 8,10 (1H, s), 8,56 (1H, d, J = 1.5 Hz), 8,67 (1H, d, J = 5,1 Hz), 12,21 (1H, s).

2-(Biphenyl-3-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,88 totaling 3.04 (4H, m), 7,10 (1H, DD, J = 8,3, 1.5 Hz), 7,15-7,24 (1H, m), 7.24 to 7,33 (4H, m), 7,41-7,46 (1H, m), 7,51-of 7.55 (2H, m), of 7.70 (1H, t, J = 7,7 Hz), 7,73 for 7.78 (2H, m), 7,92-of 8.00 (3H, m), 8,23 (1H, s), 8,70 (1H, s), 12,31 (1H, s), 13,50-14,00 (1H, usher.).

2-(Biphenyl-4-carboxamido)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,90-a 3.01 (4H, m), to 7.09 (1H, DD, J = 8,1, 1.5 Hz), 7,15-of 7.25 (1H, m), 7,25-7,30 (4H, m), 7,44 (1H, TT, J = 7,3, 1,4 Hz), 7,49-7,56 (2H, m), 7,76-7,80 (2H, m), 7,88-7,94 (2H, m), of 7.97 (1H, d, J = 8.1 Hz), 8,03-8,08 (2H, m), to 8.70 (1H, d, J = 1.5 Hz), 12,27 (1H, s).

2-((E)-3-(3,4-Acid)acrylamide)-4-phenetylamine acid

1H-NMR (DMSO-d6) δ: 2,89 are 2.98 (4H, m), 3,81 (3H, s), of 3.84 (3H, s), 6,79 (1H, d, J = 15,5 Hz), 7,00 (1H, d, J = 8.5 Hz),? 7.04 baby mortality (1H, DD, J = 8,3, 1,4 Hz), 7,15-7,20 (1H, m), 7.23 percent-7,30 (5H, m), 7,38 (1H, d, J = 1.7 Hz), 7,56 (1H, d, J = 15,5 Hz), to $ 7.91 (1H, d, J = 8,3 Hz), 8,58 (1H, d, J = 1.4 Hz), 11,30 (1H, s).

Example 522

1.0 ml triperoxonane acid are added to a solution containing 20 mg of tert-butyl 4-phenyl-2-(3-(1H-tetrazol-1-yl)benzamido)benzoate in 1.0 ml of methylene chloride, and the mixture is stirred at room te is the temperature for 1 hour. The solvent is evaporated under reduced pressure, the obtained residue is added ethyl acetate and tetrahydrofuran, and the mixture is heated to 50°C., the Insoluble matter is removed by filtration at the same temperature, and the solvent is evaporated under reduced pressure. To the obtained residue, add tetrahydrofuran, and the solid is separated by filtration, while receiving 5.0 mg of 4-phenyl-2-(3-(1H-tetrazol-1-yl)benzamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 7.48 (1H, TT, J = 7,3, 1.5 Hz), 7,53-of 7.60 (3H, m), 7,72 for 7.78 (2H, m), 7,92 (1H, t, J = 7.9 Hz), 8,15 (2H, d, J = 8,3 Hz), 8,20-8,24 (1H, m), 8,54 (1H, t, J = 1,8 Hz), 9,04 (1H, d, J = 1.7 Hz), 10,23 (1H, s)to 12.44 (1H, s).

Example 523

1.0 ml of methanol and 0.5 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l are added to a solution containing 20 mg of tert-butyl 4-phenyl-2-(4-(1H-pyrrol-1-yl)benzamido)benzoate in 1.0 ml of dioxane at room temperature, and the mixture was stirred at 50°C for 30 minutes. After cooling the reaction mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous sodium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add diisopropylethylamine, and the solid is separated by filtration, while receiving 15 mg of 4-phenyl-2-(4-(1H-pyrrol-1-yl)benzamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,34 (2H, t, J = 2.2 Hz), 7,47 (1H, TT, J = 7,3, 1.5 Hz), 7,50-to 7.59 (5H, m), 7,72 for 7.78 (2H, m), 7,83-7,88 (2H, m), 8,03-of 8.09 (2H, m), 8,15 (1H, d, J = 8.5 Hz), which is 9.09 (1H, d, J = 2.0 Hz), of 12.33 (1H, s).

Example 524

1.0 ml of methanol and 0.5 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l are added to a solution containing 20 mg of tert-butyl-4-phenoxy-2-(3-(1H-pyrrol-1-yl)benzamido)benzoate in 1.0 ml of dioxane at room temperature, and the mixture was stirred at 50°C for 30 minutes. After cooling the reaction mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining a 7.6 mg 4 phenoxy-2-(3-(1H-pyrrol-1-yl)benzamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,32 (2H, t, J = 2.2 Hz), to 6.80 (1H, DD, J = 8,9, 2.7 Hz), 7,16-7,22 (2H, m), 7,26-to 7.32 (1H, m), 7,46 (2H, t, J = 2.2 Hz), 7,47-rate of 7.54 (2H, m), 7,66 (1H, t, J = 7.9 Hz), 7,74-7,80 (1H, m), 7,84-7,88 (1H, m), 8,05 (1H, t, J = 1.8 G is), of 8.09 (1H, d, J = 8,9 Hz), 8,39 (1H, d, J = 2.7 Hz), to 12.52 (1H, s).

Example 525

1.7 ml triperoxonane acid is added to 0.17 g of tert-butyl-4-phenethyl-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoate, and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure, and to the obtained residue, add hexane and diisopropyl ether, and the solid is separated by filtration. To the obtained solid substance added ethyl acetate and water, and regulate pH to 6.8 with a saturated aqueous solution of sodium bicarbonate. The solid is separated by filtration, thus obtaining 63 mg of 4-phenethyl-2-(6-(piperidine-1-yl)pyridine-3-carboxamido)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,51 by 1.68 (6H, m), 2,88-of 2.97 (4H, m), 3,62-and 3.72 (4H, m)6,94 (1H, d, J = 9.3 Hz), 7,01 (1H, d, J = 8.1 Hz), 7,16-7,20 (1H, m), 7,25-7,30 (4H, m), 7,94 (1H, d, J = 8.0 Hz), 7,94-8,00 (1H, m), 8,65 (1H, s), 8,69 (1H, d, J = 2.4 Hz), 12,30-12,50 (1H, usher.).

Example 526

29 mg of 3,5-differenoe, 79 mg tribalista, of 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 6.8 mg of Tris(dibenzylideneacetone)diplegia(0) are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate 1.4 ml of toluene, at room temperature, and the resulting mixture is refluxed in a nitrogen atmosphere in a t is the significance of 3 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane:ethyl acetate = 10:1], while receiving 71 mg of tert-butyl 2-(benzamido)-4-(3,5-divergence)benzoate as a colourless oil.

1H-NMR (CDCl3) δ: 1,64 (9H, s), 6,56-6,63 (3H, m), of 6.73 (1H, DD, J = 8,8, 2.4 Hz), 7,50-of 7.60 (3H, m), 8,01-8,07 (3H, m), to 8.70 (1H, d, J = 2.4 Hz), 12,34 (1H, s).

Examples 527-533

Compounds shown in table 52, receive the same manner as in example 526.

Table 52

tert-Butyl 2-(benzamido)-4-(2,3-dimethylphenoxy)benzoate

1H-NMR (CDCl3) δ: of 1.61 (9H, s)a 2.12 (3H, s), of 2.33 (3H, s), 6,50 (1H, DD, J = 8,9 and 2.5 Hz), 6.89 in (1H, d, J = 7.8 Hz),? 7.04 baby mortality (1H, d, J = 7,6 Hz), 7,10-to 7.15 (1H, m), of 7.48-7,58 (3H, m), 7,94 (1H, d, J = 8,9 Hz), 8,00-with 8.05 (2H, m), 8,53 (1H, d, J = 2.5 Hz), 12,31 (1H, s).

tert-Butyl 2-(benzamido)-4-(3-fluoro-4-methylphenoxy)benzoate

1H-NMR (CDCl3) δ: of 1.62 (9H, s), and 2.26 (3H, d, J = 1.7 Hz), to 6.67 (1H, DD, J = 8,9 and 2.5 Hz), 6.75 in-6,83 (2H, m), 7,18 (1H, t, J = 8.5 Hz), of 7.48-to 7.59 (3H, m), to 7.99 (1H, d, J = 8,9 Hz), 7,9-with 8.05 (2H, m), 8,61 (1H, d, J = 2.5 Hz), 12,32 (1H, s).

tert-Butyl 2-(benzamido)-4-(3-(triptoreline)phenoxy)benzoate

1H-NMR (CDCl3) δ: 1,63 (9H, s), 6,69 (1H, DD, J = 8,9, 2.7 Hz), 6,94-6,98 (1H, m), 7,00-7,06 (2H, m), 7,39 (1H, t, J = 8,3 Hz), 7,49-of 7.60 (3H, m), 8,00-of 8.06 (3H, m), 8,67 (1H, d, J = 2.7 Hz), 12,32 (1H, s).

tert-Butyl 2-(benzamido)-4-(benzo[1,3]dioxol-5-yloxy)benzoate

1H-NMR (CDCl3) δ: of 1.61 (9H, s)to 6.00 (2H, s), to 6.58 (1H, DD, J = 8,3, 2.4 Hz), 6,61 of 6.66 (2H, m), to 6.80 (1H, d, J = 8,3 Hz), of 7.48-7,58 (3H, m), of 7.97 (1H, d, J = 9.0 Hz), 8,00-with 8.05 (2H, m), 8,56 (1H, d, J = 2.7 Hz), 12,31 (1H, s).

tert-Butyl 2-(benzamido)-4-(2,3-dihydrobenzo[1,4]dioxin-6-yloxy)benzoate

1H-NMR (CDCl3) δ: of 1.61 (9H, s), 4,27 (4H, s), 6,58 is 6.67 (3H, m), 6.87 in (1H, d, J = 8,8 Hz), of 7.48-7,58 (3H, m), of 7.96 (1H, d, J = 9.0 Hz), 8,00-with 8.05 (2H, m), to 8.57 (1H, d, J = 2.4 Hz), 12,30 (1H, s).

tert-Butyl 2-(benzamido)-4-(benzofuran-5-yloxy)benzoate

1H-NMR (CDCl3) δ: of 1.61 (9H, s), only 6.64 (1H, DD, J = 9,0, 2.7 Hz), to 6.75 (1H, DD, J = 2,2, 1.0 Hz), 7,07 (1H, DD, J = 8,8, 2.4 Hz), 7,33 (1H, d, J = 2.4 Hz), 7,47-EUR 7.57 (4H, m), 7,66 (1H, d, J = 2.2 Hz), of 7.97 (1H, d, J = 9.0 Hz), 7,98-8,04 (2H, m), 8,58 (1H, d, J = 2.7 Hz), 12,31 (1H, s).

tert-Butyl 2-(benzamido)-4-(benzothiophen-5-yloxy)benzoate

1H-NMR (CDCl3) δ: of 1.62 (9H, s), to 6.67 (1H, DD, J = 8,9 and 2.5 Hz), to 7.15 (1H, DD, J = 8,9, and 2.1 Hz), 7,27-7,30 (1H, m), of 7.48-7,58 (5H, m), 7,88 (1H, d, J = 8.5 Hz), 7,98 (1H, d, J = 8,8 Hz), 7,99-of 8.04 (2H, m), 8,63 (1H, d, J = 2.5 Hz), 12,32 (1H, s).

Example 534

6.0 mg of palladium acetate are added to the suspension containing 0.50 g of tert-butyl 2-(benzamido)-4-bromobenzoate, of 0.18 ml 3-methoxyphenol, 17 mg of 2(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 0.57 g of tribalista in 5 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 5 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with 10% aqueous citric acid solution and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane: ethyl acetate = 6:1], while receiving 0.32 g of tert-butyl 2-(benzamido)-4-(3-methoxyphenoxy)benzoate as a white solid.

1H-NMR (CDCl3) δ: of 1.62 (9H, s), of 3.80 (3H, s), 6,64-6,76 (4H, m), 7,28 (1H, t, J = 8.0 Hz), of 7.48-to 7.59 (3H, m), 7,98 (1H, d, J = 8,8 Hz), 8,01-of 8.06 (2H, m), 8,63 (1H, d, J = 2.7 Hz), 12,30 (1H, s).

Example 535

The following connection receive the same manner as in example 534.

tert-Butyl 2-(benzamido)-4-(4-methoxyphenoxy)benzoate

1H-NMR (CDCl3) δ: of 1.61 (9H, s), 3,82 (3H, s), 6,62 (1H, DD, J = 9,0, 2.7 Hz), 6.90 to-of 6.96 (2H, m), 7,02-was 7.08 (2H, m), of 7.48-7,58 (3H, m), of 7.96 (1H, d, J = 9.0 Hz), 7,99-of 8.06 (2H, m), 8,54 (1H, d, J = 2.7 Hz), 12,31 (1H, s).

Example 536

31 mg of 4-NITROPHENOL is added to suspense and, containing 8,9 mg of 60% sodium hydride in 1.0 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 15 minutes. After cooling the reaction mixture to room temperature, add a solution containing 3.8 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl, 1.3 mg of palladium acetate and 56 mg of tert-butyl 2-(benzamido)-4-bromobenzoate in 0.5 ml of toluene, and the resulting mixture is refluxed under nitrogen atmosphere for 3 hours. After cooling the reaction mixture to room temperature, add 1.3 mg of tri-tert-butylperbenzoate and 4.1 mg of Tris(dibenzylideneacetone)diplegia(0), and the resulting mixture is refluxed under nitrogen atmosphere for 4 hours. After cooling the reaction mixture to room temperature, add 10% aqueous citric acid solution and ethyl acetate, and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane: ethyl acetate = 10:1], while receiving 18 mg of tert-butyl 2-(benzamido)-4-(4-nitrophenoxy)benzo is in the form of a white solid.

1H-NMR (CDCl3) δ: 1,65 (9H, s), 6,79 (1H, DD, J = 8,8, 2.4 Hz), 7,12-7,17 (2H, m), 7,50-to 7.61 (3H, m), 8,01-of 8.06 (2H, m), of 8.09 (1H, d, J = 8,8 Hz), 8,23-8,29 (2H, m), a total of 8.74 (1H, d, J = 2.4 Hz), 12,36 (1H, s).

Example 537

26 mg of 5-hydroxy-1-methyl-1H-indole, 64 mg of tribalista, 3.8 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 5.5 mg of Tris(dibenzylideneacetone)diplegia(0) are added to a solution containing 50 mg of methyl 2-(benzamido)-4-bromobenzoate in 1.0 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane: ethyl acetate = 5:1], while receiving 53 mg of methyl 2-(benzamido)-4-(1-methyl-1H-indol-5-yloxy)benzoate as a pale yellow solid.

1H-NMR (CDCl3) δ: a 3.83 (3H, s), 3,93 (3H, s), 6,47 (1H, DD, J = 3.1 and 0.9 Hz), 6,63 (1H, DD, J = 9,0, 2.6 Hz), 7,02 (1H, DD, J = 8,8, 2.2 Hz), 7,10 (1H, d, J = 2,9 Hz), 7,32-7,38 (2H, m), 7,47-EUR 7.57 (3H, m), 7,978,03 (3H, m), 8,58 (1H, d, J = 2.6 Hz), 12,14 (1H, s).

Example 538

The following connection receive the same manner as in example 537.

Methyl-2-(benzamido)-4-(3-chlorophenoxy)benzoate

1H-NMR (CDCl3) δ: of 3.96 (3H, s)6,70 (1H, DD, J = 9,0, 2,5 Hz), 7,01 (1H, DDD, J = 8,1, 2,1, 0.9 Hz), 7,10 (1H, t, J = 2.1 Hz), 7,17 (1H, DDD, J = 8,1, 2,1, 0.9 Hz), 7,33 (1H, t, J = 8.1 Hz), of 7.48-to 7.59 (3H, m), 8,00-with 8.05 (2H, m), 8,07 (1H, d, J = 9.0 Hz), 8,65 (1H, d, J = 2.5 Hz), 12,17 (1H, s).

Example 539

The solution containing 69 mg of tert-butyl 2-(benzamido)-4-(3,5-divergence)benzoate 5.0 ml triperoxonane acid) is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, to thereby obtain 41 mg of 2-(benzamido)-4-(3,5-divergence)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,90 (1H, DD, J = 8,8, 2.4 Hz), of 6.96? 7.04 baby mortality (2H, m), 7,17 (1H, TT, J = 9,4, 2.3 Hz), 7,56-of 7.69 (3H, m), to $ 7.91-of 7.97 (2H, m)to 8.12 (1H, d, J = 8,8 Hz), 8,48 (1H, d, J = 2.7 Hz), 12,42 (1H, s).

Example 540-549

Compounds shown in table 53, receive the same manner as in example 539.

Table 53

2-(Benzamido)-4-(4-nitrophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,98 (1H, DD, J = 8,7, 2,5 Hz), 7,33-7,38 (2H, m), EUR 7.57-of 7.69 (3H, m), to $ 7.91-of 7.97 (2H, m), 8,17 (1H, d, J = 8.7 Hz), 8.30 to-836 (2H, m), 8,54 (1H, d, J = 2.5 Hz), 12,46 (1H, s).

2-(Benzamido)-4-(2,3-dimethoxyphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 2,07 (3H, s), 2,31 (3H, s), 6,63 (1H, DD, J = 8,9, 2.7 Hz), 6,94 (1H, d, J = 7,7 Hz), 7,13 (1H, d, J = 7.5 Hz), 7,17-7,22 (1H, m), 7,55-to 7.68 (3H, m), of 7.90-7,94 (2H, m), of 8.04 (1H, d, J = 8,9 Hz), with 8.33 (1H, d, J = 2.7 Hz), 12,41 (1H, s), 13,50-13,70 (1H, usher.).

2-(Benzamido)-4-(3-fluoro-4-methylphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: of 2.26 (3H, d, J = 1.7 Hz), 6,79 (1H, DD, J = 8,9, 2,5 Hz)6,94 (1H, DD, J = 8,3, 2.2 Hz), 7,07 (1H, DD, J = 10,6, and 2.3 Hz), 7,35-7,41 (1H, m), 7,56-to 7.68 (3H, m), of 7.90-of 7.95 (2H, m), 8,08 (1H, d, J = 8,9 Hz), 8,42 (1H, d, J = 2.5 Hz), 12,42 (1H, s).

2-(Benzamido)-4-(3-methoxyphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: of 3.78 (3H, s)6,70-to 6.88 (4H, m), 7,38 (1H, t, J = 8,2 Hz), 7,55-to 7.68 (3H, m), to $ 7.91-of 7.95 (2H, m), 8,07 (1H, d, J = 8,8 Hz), 8,43 (1H, d, J = 2.4 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(4-methoxyphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: with 3.79 (3H, s)of 6.71 (1H, DD, J = 8,9, 2.7 Hz), 7,01-7,06 (2H, m), 7,11-7,17 (2H, m), 7,55-to 7.68 (3H, m), 7,89-of 7.95 (2H, m), with 8.05 (1H, d, J = 8,9 Hz), at 8.36 (1H, d, J = 2.7 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(3-(triptoreline)phenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,85 (1H, DD, J = 8,8, and 2.6 Hz), 7,20-7,31 (3H, m), 7,56-of 7.69 (4H, m), of 7.90-of 7.96 (2H, m), 8,11 (1H, d, J = 8,8 Hz), 8,46 (1H, d, J = 2.6 Hz), 12,43 (1H, s).

2-(Benzamido)-4-(benzo[1,3]dioxol-5-yloxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,10 (2H, s), of 6.65 (1H, DD, J = 8,3, 2.3 Hz), was 6.73 (1H, DD, J = 8,8, 2.7 Hz), 6.87 in (1H, d, J = 2.3 Hz), of 6.99 (1H, d, J = 8,3 Hz), 7,56-to 7.68 (3H, m), of 7.90-of 7.96 (2H, m), with 8.05 (1H, d, J = 8,8 Hz), scored 8.38 (1H, d, J 2,7 Hz), 12,42 (1H, s), 13,55-of 13.75 (1H, usher.).

2-(Benzamido)-4-(2,3-dihydrobenzo[1,4]dioxin-6-yloxy)benzoic acid

1H-NMR (DMSO-d6) δ: 4,25-or 4.31 (4H, m), of 6.65 (1H, DD, J = 8,7, 2,8 Hz),6,69-6,74 (2H, m), to 6.95 (1H, d, J = 8.5 Hz), 7,56-to 7.68 (3H, m), of 7.90-of 7.96 (2H, m), with 8.05 (1H, d, J = 8,8 Hz), scored 8.38 (1H, d, J = 2.7 Hz), 12,42 (1H, s).

2-(Benzamido)-4-(benzofuran-5-yloxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,76 (1H, DD, J = 8,9 and 2.5 Hz), 7,00 (1H, DD, J = 2,2, 1.0 Hz), to 7.15 (1H, DD, J = 8,9 and 2.5 Hz), 7,49 (1H, d, J = 2.5 Hz), 7,54-to 7.67 (3H, m), 7,71 (1H, d, J = 8,9 Hz), 7,88-to 7.93 (2H, m), of 8.06 (1H, d, J = 8,9 Hz), 8,09 (1H, d, J = 2.2 Hz), 8,39 (1H, d, J = 2.5 Hz), 12,42 (1H, s), 13,50-of 13.75 (1H, usher.).

2-(Benzamido)-4-(benzothiophen-5-yloxy)benzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,9, 2.7 Hz), 7.23 percent (1H, DD, J = 8,7, and 2.3 Hz), 7,47 (1H, DD, J = 5,5, 0.6 Hz), 7,54-to 7.67 (3H, m), of 7.70 (1H, d, J = 2.3 Hz), 7,88 (1H, d, J = 5.5 Hz), 7,88-to 7.93 (2H, m), 8,08 (1H, d, J = 8,8 Hz), 8,11 (1H, d, J = 8.5 Hz), 8,42 (1H, d, J = 2.7 Hz), 12,42 (1H, s).

Example 550

0,094 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l are added to a solution containing 50 mg of methyl 2-(benzamido)-4-(1-methyl-1H-indol-5-yloxy)benzoate in 1.5 ml of dioxane and 1.5 ml of methanol at room temperature, the mixture was stirred at 50°C for 1 hour, and at the same temperature add 0,031 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l and the mixture is then stirred at 50°C for 30 minutes. After cooling the reaction mixture to room temperature, add water and regulate pH to 3.5 with hydrochloric acid with a concentration of 1.0 mol/l and add ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with water and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue, add hexane, and the solid is separated by filtration, to thereby obtain 37 mg of 2-(benzamido)-4-(1-methyl-1H-indol-5-yloxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: a-3.84 (3H, s), of 6.45 (1H, d, J = 2,9 Hz), of 6.71 (1H, DD, J = 8,8, 2.3 Hz), 6,98 (1H, DD, J = 8,8, 2.2 Hz), 7,35 (1H, d, J = 2.2 Hz), 7,42 (1H, d, J = 2,9 Hz), 7,51-to 7.67 (4H, m), 7,87-a 7.92 (2H, m), 8,03 (1H, d, J = 8,8 Hz), at 8.36 (1H, d, J = 2.3 Hz), 12,43 (1H, s), 13,45-13,70 (1H, usher.).

Example 551

0.16 ml of aqueous sodium hydroxide with a concentration of 2.0 mol/l are added to a solution containing 0.10 g of methyl 2-(benzamido)-4-(3-chlorophenoxy)benzoate in 1.0 ml of a mixture of methanol and 1.0 ml of tetrahydrofuran under ice cooling, and the mixture is stirred at room temperature for 5 hours. The reaction mixture was added to water and hydrochloric acid with a concentration of 1.0 mol/l under ice cooling, and the solid is separated by filtration, to thereby obtain 92 mg of 2-(benzamido)-4-(3-chlorophenoxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,83 (1H, DD, J = 8,8, 2.4 Hz), 7,15-to 7.18 (1H, m), 7,29-to 7.32 (1H, m), 7,33-7,37 (1H, m), 7,51 (1H, t, J = 8,2 Hz), EUR 7.57-to 7.68 (3H, m), to $ 7.91-of 7.96 (2H, m) 8,10 (1H, d, J = 8,8 Hz), 8,44 (1H, d, J = 2.4 Hz), 12,42 (1H, s), 13,59-13,92 (1H, usher.).

Example 552

0,22 g of aluminium chloride are added to a solution containing 0.10 g of 2-(benzamido)-4-(3-methoxyphenoxy)benzoic acid in 1.0 ml of toluene, at room temperature, and the mixture is stirred at 80°C for 8 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and hydrochloric acid with a concentration of 1.0 mol/L. Organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with hydrochloric acid with a concentration of 1.0 mol/l) and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane:ethyl acetate:acetic acid = 15:10:1], while receiving 54 mg of 2-(benzamido)-4-(3-hydroxyphenoxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: of 6.52 (1H, t, J = 2.2 Hz), 6,55-6,60 (1H, m), 6,64-6,70 (1H, m), is 6.78 (1H, DD, J = 8,9 and 2.5 Hz), 7,26 (1H, t, J = 8.0 Hz), 7,54-7,71 (3H, m), 7,89-to 7.99 (2H, m), 8,07 (1H, d, J = 8,9 Hz), 8,42 (1H, d, J = 2.5 Hz), made up 9.77 (1H, s), 12,43 (1H, s).

Example 553

The following connection receive the same manner as in example 552.

2-(Benzamido)-4-(4-hydroxyphenoxy)benzoic acid

1 6) δ: 6,69 (1H, DD, J = 8,8, 2.7 Hz), 6,82-to 6.88 (2H, m), 6,97? 7.04 baby mortality (2H, m), 7,54-to 7.68 (3H, m), of 7.90-of 7.95 (2H, m), 8,03 (1H, d, J = 8,8 Hz), a 8.34 (1H, d, J = 2.7 Hz), of 9.51 (1H, s)to 12.44 (1H, s).

Example 554

0,023 ml of p-cresol, 79 mg tribalista, 2.4 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 0.8 mg of palladium acetate are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate 1.4 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 1 hour. After cooling the reaction mixture to room temperature, add the 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 1.7 mg of palladium acetate and the resulting mixture is refluxed under nitrogen atmosphere for 6 hours. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [Flash Tube 2008 manufactured by Trikonex Company, eluent: hexane: ethyl acetate = 4:1], while receiving tert-butyl-2-(benzamido)-4-(4-methylphenoxy)benzoate.

5.0 ml triperoxonane acids are added to the obtained tert-BU the Il-2-(benzamido)-4-(4-methylphenoxy)benzoate and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure and the obtained residue is added methanol, and the solid is separated by filtration, thus obtaining a 6.2 mg of 2-(benzamido)-4-(4-methylphenoxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 2,35 (3H, s), 6,74 (1H, DD, J = 8,8, and 2.6 Hz), 7,05-7,10 (2H, m), 7,26-to 7.32 (2H, m), 7,56-to 7.68 (3H, m), of 7.90-of 7.95 (2H, m), with 8.05 (1H, d, J = 8,8 Hz), 8,39 (1H, d, J = 2.6 Hz), 12,43 (1H, s).

Examples 555, 556

Compounds shown in table 54, receive the same manner as in example 554.

Table 54

2-(Benzamido)-4-(2-chlorophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: was 6.73 (1H, DD, J = 8,8, 2,5 Hz), 7,33-7,42 (2H, m), 7,45-7,53 (1H, m), 7,54-7,72 (4H, m), 7,87-of 7.96 (2H, m), 8,08 (1H, d, J = 8,8 Hz), at 8.36 (1H, d, J = 2.5 Hz), 12,42 (1H, s), 13,59-at 13.84 (1H, usher.).

2-(Benzamido)-4-(4-chlorophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.4 Hz), 7.18 in-7,26 (2H, m), 7,50-of 7.69 (5H, m), 7,88-of 7.97 (2H, m), of 8.09 (1H, d, J = 8,8 Hz), 8,42 (1H, d, J = 2.4 Hz), 12,41 (1H, s), 13,60-13,85 (1H, usher.).

Example 557

0,018 ml 2,4-differenoe add to suspension containing 10 mg of 60% sodium hydride in 1 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 15 minutes. After cooling the reaction mixture to room temperature, add the solution containing the 4.7 mg of 2-(di-tert-bootinfo the eno)-2',4',6'-triisopropylphenyl, 1.7 mg of palladium acetate and 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate, in 0.5 ml of toluene, and the resulting mixture is refluxed under nitrogen atmosphere for 4 hours. After cooling the reaction mixture to room temperature, add 4.5 mg of 60% sodium hydride, to 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 1.7 mg of palladium acetate and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, add 0,018 ml 2,4-differenoe, 7.4 mg of 60% sodium hydride, to 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 1.7 mg of palladium acetate and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, add 1.6 mg three-tert-butylperbenzoate and 5.1 mg of Tris(dibenzylideneacetone)diplegia(0) and the resulting mixture is refluxed under nitrogen atmosphere for 1 hour and 30 minutes. After cooling the reaction mixture to room temperature, add 10% aqueous citric acid solution and ethyl acetate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. Obtained OST the current purified column chromatography on silica gel [Flash Tube 2008, manufactured by Trikonex Company, eluent: hexane: ethyl acetate = 4:1], while receiving tert-butyl-2-(benzamido)-4-(2,4-divergence)benzoate.

5.0 ml triperoxonane acids are added to the obtained tert-butyl 2-(benzamido)-4-(2,4-divergence)benzoate and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure and the obtained residue is added diisopropyl ether, and the solid is separated by filtration, thus obtaining 3.8 mg 2-(benzamido)-4-(2,4-divergence)benzoic acid as a pale yellow solid.

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,8, 2.7 Hz), 7,20-7,28 (1H, m), 7,46-7,52 (1H, m), 7,54-to 7.68 (4H, m), of 7.90-of 7.95 (2H, m), 8,07 (1H, d, J = 8,8 Hz), scored 8.38 (1H, d, J = 2.7 Hz), to 12.44 (1H, s).

Example 558

52 mg of tert-butyl-5-hydroxy-1H-indole-1-carboxylate, 79 mg tribalista, of 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 6.8 mg of Tris(dibenzylideneacetone)diplegia(0) are added to a solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate 1.4 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours and 30 minutes. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution and the insoluble matter is removed filtervariablename layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane: ethyl acetate = 10:1], while receiving tert-butyl-5-(3-(benzamido)-4-(tert-butoxycarbonyl)phenoxy)-1H-indole-1-carboxylate.

1.0 ml triperoxonane acid are added to a solution containing the obtained tert-butyl-5-(3-(benzamido)-4-(tert-butoxycarbonyl)phenoxy)-1H-indole-1-carboxylate 4.0 ml of methylene chloride under ice cooling, and the mixture was stirred at the same temperature for 2 hours and 30 minutes. After heating the reaction mixture to room temperature, add ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated and washed with ethyl acetate after the establishment of the pH to 6.5 with hydrochloric acid with a concentration of 6.0 mol/l, and the mixture was incubated for 17 hours. The solid is separated by filtration, while receiving 10 mg of 2-(benzamido)-4-(1H-indol-5-yloxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,41-to 6.43 (1H, m), is 6.54 (1H, DD, J = 8,6, 2.7 Hz), 6.87 in (1H, DD, J = 8,6, and 2.3 Hz), 7,25 (1H, d, J = 2.2 Hz), 7,39-7,41 (1H, m), the 7.43 (1H, d, J = 8.5 Hz), 7,46-to 7.59 (3H, m), of 7.96-of 8.04 (3H, m), 8,30 (1H, d, J = 2,4 Hz), 11,19 (1H, s).

Example 559

31 mg of 3-NITROPHENOL, 79 mg tribalista, of 4.7 mg of 2-(di-tert-bootyvote is about)-2',4',6'-triisopropylphenyl and 6.8 mg of Tris(dibenzylideneacetone)diplegia(0) are added to a solution, containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate 1.4 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 2 hours. After cooling the reaction mixture to room temperature, add the 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 6.8 mg of Tris(dibenzylideneacetone)diplegia(0) and the resulting mixture is refluxed under nitrogen atmosphere for 1 hour. After cooling the reaction mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution and the insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane: ethyl acetate = 10:1], while receiving tert-butyl-2-(benzamido)-4-(3-nitrophenoxy)benzoate.

5.0 ml triperoxonane acids are added to the obtained tert-butyl 2-(benzamido)-4-(3-nitrophenoxy)benzoate, and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure, the obtained residue is added diisopropyl ether, and the solid ve is estvo separated by filtration, while receiving 34 mg of 2-(benzamido)-4-(3-nitrophenoxy)benzoic acid as a pale yellow solid.

1H-NMR (DMSO-d6) δ: 6,91 (1H, DD, J = 8,8, and 2.6 Hz), 7,56-7,71 (4H, m), 7,78 (1H, t, J = 8,2 Hz), of 7.90-7,98 (3H, m), 8,10-8,16 (2H, m), 8,49 (1H, d, J = 2.6 Hz), 12,41 (1H, s).

Examples 560-570

Compounds shown in table 55, receive the same manner as in example 559.

Table 55

2-(Benzamido)-4-(4-pertenece)benzoic acid

1H-NMR (DMSO-d6) δ: 6,76 (1H, DD, J = 8,9, 2.7 Hz), 7,21-7,28 (2H, m), 7,29-7,37 (2H, m), 7,55-to 7.68 (3H, m), of 7.90-of 7.95 (2H, m), 8,07 (1H, d, J = 8,9 Hz), 8,39 (1H, d, J = 2.7 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(4-(triptoreline)phenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: PC 6.82 (1H, DD, J = 8,9, 2.7 Hz), 7,28-7,34 (2H, m), 7,46-7,52 (2H, m), 7,56-of 7.69 (3H, m), of 7.90-of 7.96 (2H, m), 8,10 (1H, d, J = 8,9 Hz), 8,44 (1H, d, J = 2.7 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(2-methylphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 2,16 (3H, s), to 6.67 (1H, DD, J = 8,9, 2.7 Hz), 7,08-7,13 (1H, m), 7,21-7,26 (1H, m), 7,29-7,34 (1H, m), 7,38-7,41 (1H, m), 7,55-to 7.68 (3H, m), 7,89-of 7.95 (2H, m), with 8.05 (1H, d, J = 8,9 Hz), 8,32 (1H, d, J = 2.7 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(3-methylphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: of 2.34 (3H, s)6,76 (1H, DD, J = 9,0, 2.6 Hz), 6,94-7,02 (2H, m), 7,07 for 7.12 (1H, m), of 7.36 (1H, DD, J = 8.0 a, 7,7 Hz), 7,56-to 7.68 (3H, m), of 7.90-of 7.96 (2H, m), 8,07 (1H, d, J = 9.0 Hz), to 8.41 (1H, d, J = 2.6 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(2,6-dimethylphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 2,10 (6H, s), 6,58 (H, DD, J = 9,0, 2,5 Hz), 7,14-of 7.25 (3H, m), 7,55-to 7.68 (3H, m), 7,89-of 7.95 (2H, m), of 8.04 (1H, d, J = 9.0 Hz), of 8.25 (1H, d, J = 2.5 Hz), 12,43 (1H, s).

2-(Benzamido)-4-(3-pertenece)benzoic acid

1H-NMR (DMSO-d6) δ: at 6.84 (1H, DD, J = 8,8, 2.4 Hz), 7,00-7,05 (1H, m), 7,08-7,16 (2H, m), of 7.48-to 7.68 (4H, m), of 7.90-of 7.96 (2H, m), 8,10 (1H, d, J = 8,8 Hz), to 8.45 (1H, d, J = 2.4 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(2-pertenece)benzoic acid

1H-NMR (DMSO-d6) δ: 6,79 (1H, DD, J = 8,8, and 2.6 Hz), 7,29-7,51 (4H, m), 7,55-of 7.69 (3H, m), 7,89-of 7.95 (2H, m), 8,08 (1H, d, J = 8,8 Hz), 8,39 (1H, d, J = 2.6 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(2,6-divergence)benzoic acid

1H-NMR (DMSO-d6) δ: 6,85 (1H, DD, J = 9,0, 2.7 Hz), 7,34-7,51 (3H, m), 7,55-to 7.68 (3H, m), 7,89-of 7.95 (2H, m), of 8.09 (1H, d, J = 9.0 Hz), 8,42 (1H, d, J = 2.7 Hz), 12,43 (1H, s).

2-(Benzamido)-4-(3,4-dimethylphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 2,24 (6H, s), 6,72 (1H, DD, J = 8,9, 2.7 Hz), 6.89 in (1H, DD, J = 8,1, 2,5 Hz), 6,98 (1H, d, J = 2.5 Hz), 7.23 percent (1H, d, J = 8.1 Hz), 7,56-to 7.68 (3H, m), of 7.90-of 7.95 (2H, m), with 8.05 (1H, d, J = 8,9 Hz), 8,39 (1H, d, J = 2.7 Hz), 12,40 (1H, s).

2-(Benzamido)-4-(3-(trifluoromethyl)phenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,85 (1H, DD, J = 9,0, 2.7 Hz), of 7.48-7,52 (1H, m), 7,54-to 7.68 (5H, m), 7,72 (1H, t, J = 7.9 Hz), of 7.90-of 7.95 (2H, m), 8,11 (1H, d, J = 9.0 Hz), 8,46 (1H, d, J = 2.7 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(4-(trifluoromethyl)phenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,90 (1H, DD, J = 8,8, and 2.6 Hz), 7,33-7,39 (2H, m), 7,56-of 7.69 (3H, m), 7,81-7,88 (2H, m), to $ 7.91-of 7.96 (2H, m), 8,13 (1H, d, J = 8,8 Hz)and 8.50 (1H, d, J = 2.6 Hz), 12,41 (1H, s), 13,70-13,95 (1H, usher.).

Example 571

91 mg of 2,4-dichlorphenol added to the suspension containing 22 mg of 60% sodium hydride in 2.1 ml of toluene, at room temperature, and the resulting mixture is refluxed under nitrogen atmosphere for 15 minutes. After cooling the reaction mixture to room temperature, add 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate, of 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 6.8 mg of Tris(dibenzylideneacetone)diplegia(0) and the resulting mixture is refluxed under nitrogen atmosphere for 6 hours. After cooling the reaction mixture to room temperature, add 61 mg of 2,4-dichlorphenol, 15 mg of 60% sodium hydride, to 4.7 mg of 2-(di-tert-butylphosphino)-2',4',6'-triisopropylphenyl and 6.8 mg of Tris(dibenzylideneacetone)diplegia(0) and the resulting mixture is refluxed under nitrogen atmosphere for 10 hours. After cooling the reaction mixture to room temperature, add 10% aqueous citric acid solution and ethyl acetate and insoluble matter is removed by filtration. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: GE is San:ethyl acetate = 20:1], while receiving tert-butyl-2-(benzamido)-4-(2,4-dichlorophenoxy)benzoate.

5.0 ml triperoxonane acid is added to the obtained tert-butyl 2-(benzamido)-4-(2,4-dichlorophenoxy)benzoate and the mixture is stirred at room temperature for 2 hours. The solvent is evaporated under reduced pressure and the resulting residue is purified column chromatography on silica gel with reversed phase [eluent: aqueous solution 80-100% acetonitrile/0.1% of triperoxonane acid], while receiving 8,7 mg of 2-(benzamido)-4-(2,4-dichlorophenoxy)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 6,77 (1H, DD, J = 8,8, 2.7 Hz), 7,41 (1H, d, J = 8,8 Hz), 7,53-to 7.68 (4H, m), 7,88 (1H, d, J = 2.4 Hz), of 7.90-of 7.95 (2H, m), 8,08 (1H, d, J = 8,8 Hz), at 8.36 (1H, d, J = 2.7 Hz), 12,43 (1H, s).

Examples 572-583

Compounds shown in table 56, receive the same manner as in example 571.

Table 56

2-(Benzamido)-4-(2,3-divergence)benzoic acid

1H-NMR (DMSO-d6) δ: 6,86 (1H, DD, J = 8,9, 2.7 Hz), 7,20-7,26 (1H, m), 7,30-of 7.48 (2H, m), 7,56-to 7.68 (3H, m), of 7.90-of 7.95 (2H, m), 8,10 (1H, d, J = 8,9 Hz), 8,44 (1H, d, J = 2.7 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(3-chloro-2-pertenece)benzoic acid

1H-NMR (DMSO-d6) δ: at 6.84 (1H, DD, J = 8,8, 2.7 Hz), 7,32-the 7.43 (2H, m), 7,53-of 7.69 (4H, m), of 7.90-of 7.96 (2H, m), 8,10 (1H, d, J = 8,8 Hz), 8,43 (1H, d, J = 2.7 Hz), 12,42 (1H, s).

2-(Benzamido)-4-(3-chloro-4-pertenece)benzoic acid

1H-NMR (DMSO-d 6) δ: for 6.81 (1H, DD, J = 8,8, 2.7 Hz), 7,21-7,28 (1H, m), 7,52-of 7.69 (5H, m), of 7.90-of 7.96 (2H, m), of 8.09 (1H, d, J = 8,8 Hz), 8,42 (1H, d, J = 2.7 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(3,5-dichlorophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,88 (1H, DD, J = 8,8, and 2.6 Hz), 7,32 (2H, d, J = 1.9 Hz), 7,52 (1H, t, J = 1.9 Hz), 7,56-of 7.69 (3H, m), to $ 7.91-of 7.97 (2H, m)to 8.12 (1H, d, J = 8,8 Hz), 8,46 (1H, d, J = 2.6 Hz), 12,42 (1H, s).

2-(Benzamido)-4-(4-fluoro-2-methylphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 2,15 (3H, s), to 6.67 (1H, DD, J = 8,9 and 2.5 Hz), 7,11-7,20 (2H, m), 7,27-7,31 (1H, m), 7,55-to 7.68 (3H, m), 7,89-of 7.95 (2H, m), with 8.05 (1H, d, J = 8,9 Hz), 8,31 (1H, d, J = 2.5 Hz), 12,43 (1H, s).

2-(Benzamido)-4-(3,4-divergence)benzoic acid

1H-NMR (DMSO-d6) δ: for 6.81 (1H, DD, J = 8,8, 2.7 Hz),? 7.04 baby mortality-7,11 (1H, m), 7,42-of 7.48 (1H, m), 7,52-of 7.69 (4H, m), of 7.90-of 7.96 (2H, m), of 8.09 (1H, d, J = 8,8 Hz), 8,42 (1H, d, J = 2.7 Hz), 12,42 (1H, s).

2-(Benzamido)-4-(2,5-divergence)benzoic acid

1H-NMR (DMSO-d6) δ: at 6.84 (1H, DD, J = 8,8, 2.7 Hz), 7,21-7,28 (1H, m), 7,38-7,44 (1H, m), 7,51-of 7.69 (4H, m), of 7.90-of 7.96 (2H, m), of 8.09 (1H, d, J = 8,8 Hz), 8,43 (1H, d, J = 2.7 Hz), 12,42 (1H, s).

2-(Benzamido)-4-(5-chloro-2-methylphenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 2,15 (3H, s), 6,72 (1H, DD, J = 8,9, 2.7 Hz), 7,22 (1H, d, J = 2.2 Hz), 7,30 (1H, DD, J = 8,3, 2.2 Hz), 7,44 (1H, d, J = 8,3 Hz), 7,55-to 7.68 (3H, m), of 7.90-of 7.95 (2H, m), 8,08 (1H, d, J = 8,9 Hz), a 8.34 (1H, d, J = 2.7 Hz), 12,42 (1H, s).

2-(Benzamido)-4-(3,4-dichlorophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,86 (1H, DD, J = 9,0, 2,5 Hz), 7,22 (1H, DD, J = 8,9, 2.7 Hz), 7,54-of 7.69 (4H, m), 7,74 (1H, d, J = 8,9 Hz), of 7.90-of 7.96 (2H, m), 8,10 (1H, d, J = 9.0 Hz), to 8.45 (1H, q, j = 2.5 Hz), 12,41 (1H, s).

2-(Benzamido)-4-(2,3-dichlorophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,8, and 2.6 Hz), was 7.36 (1H, DD, J = 8,3, 1.2 Hz), to 7.50 (1H, t, J = 8,2 Hz), 7,56-of 7.69 (4H, m), of 7.90-of 7.96 (2H, m), of 8.09 (1H, d, J = 8,8 Hz), scored 8.38 (1H, d, J = 2.6 Hz), to 12.44 (1H, s).

2-(Benzamido)-4-(2,5-dichlorophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: is 6.78 (1H, DD, J = 8,9, 2.7 Hz), 7,46 (1H, DD, J = 8,8, 2,5 Hz), 7,54 (1H, d, J = 2.5 Hz), 7,56-of 7.69 (3H, m), 7,73 (1H, d, J = 8,8 Hz), of 7.90-of 7.96 (2H, m), of 8.09 (1H, d, J = 8,9 Hz), scored 8.38 (1H, d, J = 2.7 Hz), 12,41 (1H with).

2-(Benzamido)-4-(2,6-dichlorophenoxy)benzoic acid

1H-NMR (DMSO-d6) δ: 6,70 (1H, DD, J = 8,8, 2.7 Hz), 7,46 (1H, t, J = 8,3 Hz), 7,55-to 7.68 (3H, m), 7,71 (2H, d, J = 8,3 Hz), 7,89-of 7.96 (2H, m), 8,08 (1H, d, J = 8,8 Hz), 8,31 (1H, d, J = 2.7 Hz), 12,49 (1H, s).

Example 584

86 mg of 4-phenylpiperidine and 0.22 g of cesium carbonate, 2.4 mg of Tris(dibenzylideneacetone)diplegia(0), 1.2 mg of palladium acetate and 6.3 mg 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl added to a solution containing 0.10 g of tert-butyl 2-(benzamido)-4-bromobenzoate in 3.0 ml of toluene, and the resulting mixture is refluxed for 2 hours. After cooling the reaction mixture to room temperature, add 2.4 mg of Tris(dibenzylideneacetone)diplegia(0), 1.2 mg of palladium acetate and 6.3 mg 2-dicyclohexylphosphino-2',4',6'-triisopropylphenyl, and the resulting mixture is refluxed for 6 hours. After cooling, actionnow mixture to room temperature, add ethyl acetate and 10% aqueous citric acid solution. The organic layer is separated and dried over anhydrous magnesium sulfate after washing with a saturated aqueous solution of sodium chloride, and the solvent is evaporated under reduced pressure. The resulting residue is purified column chromatography on silica gel [PSQ100B (spherical)manufactured by Fuji Silysia Chemical Ltd., eluent: hexane: ethyl acetate = 10:1], while receiving tert-butyl-2-(benzamido)-4-(4-phenylpiperazin-1-yl)benzoate as a pale yellow solid.

5.0 ml triperoxonane acids are added to the obtained tert-butyl 2-(benzamido)-4-(4-phenylpiperazin-1-yl)benzoate and the mixture is stirred at room temperature for 3 hours. The solvent is evaporated under reduced pressure, the obtained residue is added ethyl acetate and water, and the pH is adjusted to 6.5 with a saturated aqueous solution of sodium bicarbonate. The organic layer is separated and dried over anhydrous magnesium sulfate after washing successively with water and saturated aqueous sodium chloride, and the solvent is evaporated under reduced pressure. To the obtained residue is added diisopropyl ether and the solid is separated by filtration, thus obtaining 20 mg of 2-(benzamido)-4-(4-phenylpiperazin-1-yl)benzoic acid as a white solid.

1H-NMR (DMSO-d6) δ: 1,65-of 1.78 (2H, m), 1,86-of 1.95 (2H, m), was 2.76-2,87 (1H, m), 2,97-is 3.08 (2H, m), 4,01-4,11 (2H, m), is 6.78 (1H, DD, J = 9,1 2,5 Hz), 7,17-of 7.23 (1H, m), 7,25-7,34 (4H, m), 7,56-to 7.68 (3H, m), 7,88 (1H, d, J = 9.1 Hz), 7,94-to 7.99 (2H, m), of 8.47 (1H, d, J = 2.5 Hz), of 12.53 (1H, s).

Examples 585-588

Compounds shown in table 57, receive the same manner as in example 584.

Table 57

2-(Benzamido)-4-(1,2,3,4-tetrahydroisoquinoline-2-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 2,95-a 3.01 (2H, m), 3,64-3,70 (2H, m), 4,58 (2H, s), 6,77 (1H, DD, J = 9,0, 2.6 Hz), 7.18 in-to 7.32 (4H, m), EUR 7.57-to 7.68 (3H, m), of 7.90 (1H, d, J = 9.0 Hz), 7,95-of 8.00 (2H, m), to 8.45 (1H, d, J = 2.6 Hz), of 12.53 (1H, s), 12,97 (1H, s).

2-(Benzamido)-4-(4-benzylpiperidine-1-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 1,17 to 1.31 (2H, m), 1,62-1,71 (2H, m), 1,74-of 1.88 (1H, m), 2,50-to 2.57 (2H, m), 2,82 of 2.92 (2H, m), 3,86-of 3.96 (2H, m), 6,69 (1H, DD, J = 9,3, 2,5 Hz), 7,16-7,22 (3H, m), 7,26-to 7.32 (2H, m), 7,56-to 7.67 (3H, m), 7,84 (1H, d, J = 9.3 Hz), 7,92-7,98 (2H, m), 8,39 (1H, d, J = 2.5 Hz), 12,49 (1H, s), 12,94 (1H, s).

2-(Benzamido)-4-(4-benzoylpiperidine-1-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 1,58-1,72 (2H, m), 1,86-of 1.95 (2H, m), 3,10-is 3.21 (2H, m), of 3.73-a 3.83 (1H, m), 3,93-a 4.03 (2H, m), 6,76 (1H, DD, J = 9,1, 2.4 Hz), 7,53-of 7.70 (6H, m), 7,87 (1H, d, J = 9.1 Hz), 7,93-7,98 (2H, m), 8,01-of 8.06 (2H, m), 8,43 (1H, d, J = 2.4 Hz), 12,49 (1H, s), 12,90-13,15 (1H, usher.).

2-(Benzamido)-4-(4-phenyl-1,2,3,6-tetrahydropyridine-1-yl)benzoic acid

1H-NMR (DMSO-d6) δ: 2,64-of 2.72 (2H, m), 3,65-3,71 (2H, m), as 4.02-4.09 to (2H, m), 6,32-6,37 (1H, m), is 6.78 (1H, DD, J = 9,1, 2,5 Hz), 7,25-to 7.32 (1H, m), 7,35-7,41 (2H, m), of 7.48-7,53 (2H, m), EUR 7.57-to 7.68 (3H, m), of 7.90 (1H, d, J = 9.1 Hz), 7,95-of 8.00 (2H, m), of 8.47 (1H, d, J = 2.5 Hz), of 12.53 (1H, s), 12,90-13,15 (1H, usher.).

Industrial applicability

With the unity of the General formula [1] of the present invention or their salts have activity inhibiting the production of MMP-13 and therefore they are suitable as, for example, therapeutic agents for the treatment of rheumatoid arthritis, osteoarthritis, cancer and other diseases involving MMP-13.

1. Derivative of Anthranilic acid represented by the General formula:
[formula 1]

where R1represents a hydrogen atom or carboxyamide group selected from C1-3of alkyl;
R2represents phenyl,3-6cycloalkyl, saturated or unsaturated 5-6-membered heterocyclic group containing 1-3 heteroatoms selected from N, O and S, which may be condensed with a phenyl that may be optionally substituted C1-6the alkyl, C1-6alkoxy, acetyl, acetoxy, halogen, Halogens1-6by alkyl, nitro-group, a hydroxyl group, CN, amino, phenyl, saturated or unsaturated 5-6-membered heterocyclic group containing 1-4 heteroatoms selected from N, O, S, which can be tizamidine C1-6by alkyl;
R3represents phenyl,3-6cycloalkyl,5cycloalkenyl, saturated or unsaturated 5-6-membered heterocyclic group containing 1-3 heteroatoms selected from N, O and S, which may be condensed with phenyl (except benzoxazole), which may not be battelino substituted C 1-6the alkyl, C1-6alkoxy, phenyl, acetyl, halogen, Halogens1-6the alkyl, Halogens1-6alkoxy, nitro-group, a hydroxyl group, hydroxys1-6the alkyl, CN, acetylamino, keto, phenoxy, benzoyl, benzyl, amino group, which may be tizamidine C1-6the alkyl, carboxypropyl, C1-6alkylsulfonyl group or pyrrolidon;
X1represents a carbonyl group or sulfonyloxy group;
X2represents a C1-3alkylenes,2-3alkenylamine or2-3alkynylamino group which may be optionally substituted C1-3the alkyl, or a bond; provided that when X1represents sulfonyloxy group and X4represents a bond, X2represents a C1-3alkylenes,2-3alkenylamine or2-3alkynylamino group which may be optionally substituted C1-3by alkyl;
X3represents an oxygen atom or a bond; and
X4represents a group represented by the General formula-X5-X6or X6-X5-,
where is the link on the left side of each General formula attached to R3;
X5represents an oxygen atom, a sulfur atom, aminogroup, which may be optionally protected, or a bond; and
X6is the Wallpaper With 1-4alkylenes,2-3alkenylamine or2-3alkynylamino group, or Association,
or its pharmaceutically acceptable salt.

2. Derivative of Anthranilic acid or its pharmaceutically acceptable salt according to claim 1, where X1represents a carbonyl group.

3. Derivative of Anthranilic acid or its pharmaceutically acceptable salt according to claim 1 or 2, where R1represents a hydrogen atom; R2represents phenyl or a saturated or unsaturated 5-6-membered heterocyclic group containing 1-3 heteroatoms selected from N, O and S, which may be condensed with a phenyl that may be optionally substituted with halogen, a cyano, a nitro-group, a hydroxyl group, a C1-6the alkyl, C1-6alkoxy, phenyl or a saturated or unsaturated 5-6-membered heterocyclic group containing 1-4 heteroatoms selected from N, O, S, which can be tizamidine C1-6by alkyl; R3represents phenyl or a saturated or unsaturated 5-6-membered heterocyclic group containing 1-3 heteroatoms selected from N, O and S, which may be condensed with phenyl (except benzoxazole), which may be optionally substituted with halogen, a hydroxyl group, a C1-6the alkyl or C1-6alkoxy; X2represents a C1-3the alkyl is new, With2-3alkenylamine,2-3alkynylamino group or a bond; provided that when X1represents sulfonyloxy group and X4represents a bond, X2represents a C1-3alkylenes,2-3alkenylamine or2-3alkynylamino group; X3represents an oxygen atom or a bond; and X4represents a group of General formula-X6-X5-where the link on the left side of the General formula attached to R3;
X5represents an oxygen atom, a sulfur atom, aminogroup, which may be optionally protected, or a bond; and X6represents a C1-4alkylenes,2-3alkenylamine or2-3alkynylamino group or Association.

4. Derivative of Anthranilic acid or its pharmaceutically acceptable salt according to claim 1, where R3represents a phenyl group, nitrogen-containing bicyclic heterocyclic group selected from indolines, indolenine, 2-oxoindole, isoindolines, indolizinyl, benzimidazolyl, benzotriazolyl, indazolinone, chinoline, tetrahydropyrimidines, tetrahydroisoquinolines, chinoiseries, isohynolines, phthalazinone, khinoksalinona, dihydroisoquinoline, chineselovelinks, cinnolines and 2,3-dihydrobenzofuranyl group,oxygen-containing bicyclic heterocyclic group, selected from benzofuranyl, isobenzofuranyl, romanillos, romanillos, isoproterenol, benzo-1,3-dioxolanes, benzo-1,4-dioxanone and 2,3-dihydrobenzofuranyl group, or a sulfur-containing bicyclic heterocyclic group selected from benzothiazole and 2,3-dihydrobenzofuranyl group; and these groups may be optionally substituted with halogen, a hydroxyl group, a C1-6the alkyl, Halogens1-6the alkyl, C1-6alkoxy or Halogens1-6alkoxy.

5. Derivative of Anthranilic acid or its pharmaceutically acceptable salt according to claim 1, where X4represents a group of General formula-X6p-X5q-where the link on the left side of the General formula attached to R3; and X5qrepresents an oxygen atom, a sulfur atom or a bond, and X6prepresents a C1-4alkylenes,2-3alkenylamine or2-3alkynylamino group.

6. Derivative of Anthranilic acid or its pharmaceutically acceptable salt according to claim 1, where X4represents a group of General formula-X6r-X5s-where the link on the left side of the General formula attached to R3; and X5srepresents an oxygen atom or a bond; and X6rthat is the link.

7. The inhibitor of the production of metalloprotease 13 matrix representing the derivative and trenirovki acid or its pharmaceutically acceptable salt according to claims 1-6.

8. therapeutic agent representing a derivative of Anthranilic acid or its pharmaceutically acceptable salt according to claims 1 to 6 to obtain drugs for the treatment of rheumatoid arthritis.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of obtaining compounds of formula ,

involving reaction of a mixture of a compound of formula IVa and a compound of formula IVb

with a compound of formula

or pharmaceutically acceptable salt thereof in the presence of KOH, NaOH and LiOH as bases, and dialkylphosphite reducing agent, a tetraalkyl ammonium chloride phase transition catalyst; and possibly washing the formula II compound with a solvent and then possibly conversion of the formula II compound to a pharmaceutically acceptable salt. The invention also relates to the method of obtaining formula compounds.

EFFECT: design of a new method of obtaining a compound used as an intermediate product in irbesartan synthesis.

3 ex

FIELD: medicine.

SUBSTANCE: there is described new compound - choline salt 2-(3,4-dimethylphenyl)-4-{[2-hydroxy-3'-(1H-tetrazole-5-yl)biphenyl-3-yl]hydrazono}-5-methyl-2,4-dihydropyrazole-3-one, a pharmaceutical composition containing it, and method for making said composition.

EFFECT: new compound is an improved thrombopoietin mimetic and can be used as a TRO-receptor agonist.

3 cl, 4 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of formula (I) and to its pharmaceutically acceptable acid-additive salts. The compounds under the present invention are active to bind cannabinoid (CB) receptor. In general formula (I) , X stands for -S-, -S(=O)-, -S(=O)2-, -S(=O)2N(H)-, -P(=O)(OCH3)-, -P(=O)(OH)-, -N(H)-, -N(CH3)-, -N(H)C(=O)N(H)-, -C(=O)-, -C(=O)O-, -N(H)C(=O)-, -C(H)(OH)-, -C(H)=N-, -C(H)=C(H)-, -CH2N(H)-or -C(=NH)-; R1 stands for phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, indolyl, quinolinyl, 1,2,3,4-tetrahydroquinolinyl, isoquinolinyl, benzimidazolyl, 2-oxo-1,3-dihydrobenzimidazolyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl or indanyl which can be optionally substituted; R2 stands for hydrogen, -OR4 or -N(R5)R6; R3 stands for hydrogen; cyano; oxadiazolyl, piperazinyl or tetrazolyl optionally substituted with methyl; -C(=O)R7, -OR8 or N(R9)R10. Besides, the invention concerns method of producing compound of formula I and to pharmaceutical composition active to bind cannabinoid (CB) receptor, containing compound of formula I as an active component.

EFFECT: higher efficiency of compounds.

5 cl, 14 ex

FIELD: medicine.

SUBSTANCE: new derivatives of diphenyl urea having general formula I or their pharmaceutically comprehensible salts, where Ro - hydrogen are described; Rm - hydrogen or trifluoromethyl; Rp - hydrogen, halogeno, trifluoromethyl, trifluoromethoxy, C1-6alkyl or C1-6alkoxy; provided that Ro, Rm and Rp simultaneously cannot mean hydrogen; R2, R3, R4 and R5 independently mean hydrogen, halogeno or trifluoromethyl, provided that the bond does not represent N-(3-trifluoromethyl-phenyl)-N'-[3-(1N-tetrazole-5-il)-4'-trifluoromethyl-biphenyl-4-il]-urea, a pharmaceutical composition, their containing, and their application as blockers of chloride channels.

EFFECT: rising of efficiency of a composition and its application in medicine.

12 cl, 3 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: compound of general formula IIa or its salt, where R1 is hydrogen or protection group of tetrazol, undergoes reaction with compound of formula or its salt, where R2 is hydrogen or carboxy protection group, under conditions of reduction amination, with further acylation of obtained compound of formula or its salt by compound of formula , where R3 is the group to be separated; and with removal of protection groups if required.

EFFECT: new compounds with useful biological properties.

12 cl, 11 ex

FIELD: chemistry.

SUBSTANCE: novel compounds of formulas , , , , , , (designation of all groups are given in invention formula) are used for treatment of different metabolic diseases, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver, cachexia, obesity, atherosclerosis and arteriosclerosis.

EFFECT: using compounds as biologically active agent and creating pharmaceutical compositions based on said compounds.

124 cl, 52 ex, 17 tbl, 2 dwg

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention describes novel compounds of the general formula (I): wherein R1 means quinolinyl possibly substituted with (C1-C5)-alkoxy-group, isoquinolinyl, quinoxalinyl, pyridinyl, pyrazinyl, benzyl possibly substituted with halogen atom, naphthalinyl, thiophenyl, furanyl, cinnolyl, phenylvinyl, quinolylvinyl or 4-oxo-4H-chromenyl possibly substituted with halogen atom, (C1-C5)-alkyl or (C1-C5)-alkoxy-group; R2, R5, R8 and R11 mean hydrogen atom; R3 and R4 mean halogen atom, (C1-C5)-alkoxy-group; R6 and R7 mean hydrogen atom (H) or (C1-C5)-alkyl or form in common radical -CH2-CH2-; R9 and R10 mean (C1-C5)-alkoxy-group; m and n mean a whole number from 0 to 4 independently; X means -CH2- or sulfur atom (S). Also, invention describes their pharmaceutically acceptable salts, a method for their preparing and pharmaceutical composition based on thereof. Proposed compounds are inhibitors of P-glycoprotein, enhance bioavailability of anti-cancer drug and can be used in medicine.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical composition.

7 cl, 3 tbl, 33 ex

FIELD: organic chemistry.

SUBSTANCE: invention describes novel substituted benzoylcyclohexenones of the general formula (I): wherein values Q, Y, Z, R1-R5 and their possible tautomeric forms and their possible salts given in the invention claim. Invention proposes substituted benzoylcyclohexenones of the general formula (I) that possess the herbicide activity.

EFFECT: valuable property of compounds.

2 cl, 10 tbl, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel α-(N-sulfonamido)acetamides of the formula (I) or their optical isomers wherein values R1, R, R2 and R3 are given in the invention claim. Proposed compounds are inhibitors of production of β-amyloid peptide and can be used for inhibition of production of β-amyloid peptide. Also, invention relates to pharmaceutical composition based on these compounds and to a method for inhibition of production of β-amyloid peptide.

EFFECT: valuable medicinal property of compounds and pharmaceutical composition.

22 cl, 23 sch, 4 tbl, 501 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes derivatives of tetrazole of the general formula (I): wherein R1 means independently halogen atom, methyl, methoxyl, (C1-C3)-alkylsulfonyl, nitro- or cyano-group; R2 means (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-halogenalkyl or (C2-C6)-alkenyl; m = 0, 1 or 2; n = 1 or 2; Q means one of the following groups: (Q-1) (Q-2) (Q-3) or (Q-6) wherein R9 means hydrogen, halogen atom or (C1-C4)-alkyl; k = 1; R11 means halogen atom. Also, invention relates to a fungicide composition based on their base and an intermediate compound of the formula: wherein R1, R2, m and n are given in claim 1; W means hydroxyl, (C1-C4)-alkoxyl or group of the formula:

EFFECT: valuable properties of compounds and composition.

7 cl, 6 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention refers to chemical industry, i.e. to the new chemical compounds 4-(1-benzotriazole)-5-(naphtaoxy)-phtalodinitriles of the general formula in which R stands for as the basic for synthesis of copper tetra-4-(1-benzotriazole) tetra-5(2-naphtaoxy)phthalocyanine and copper tetra-4-(1-benzotriazole) tetra-5(1-naphtaoxy)phthalocyanine which are the solvent dyes for waxes, synthetic fiber, polymers, hydrocarbons, fats, alcohols, plastic materials and resin elastic colouring.

EFFECT: end dyes are dissolved effectively in organic environments.

1 cl, 4 dwg, 5 ex

FIELD: chemistry of polymers, chemical technology.

SUBSTANCE: invention relates to sulfoxides or sulfones grafted on polymers, polymeric compositions, a method for grafting and method for stabilization of polymers. Invention describes polymers comprising a grafted compound of the formula (I): [R1-SOm]n-R-SOp-R2 (I) wherein total symbols have values given in cl. 1 of the invention claim and represents a composition comprising thereof, a method for grafting compound of the formula (I) on polymers and a method for stabilization of polymers. Polymers comprising grafted sulfoxides or sulfones possess high stability against oxidative, thermal, dynamic destruction caused by the light effect and/or destruction caused by ozone effect.

EFFECT: improved preparing method, improved and valuable properties of polymers.

14 cl, 14 tbl, 24 ex

FIELD: synthesis of lubricant oiliness addends.

SUBSTANCE: claimed method includes reaction of equimolar amounts of 1-(N,N-dimethylaminomethyl)-benzotriazol and O-(n-butyl)-O-(3,4,5-trithiatricyclodez-8-yl-methyl))-dithiophosphoric acid at 80-100°C in toluene medium for 2-4 h to produce target product of general formula:

.

EFFECT: ash-free addend for lubricant oils processing under high pressure, in particular lubricant oiliness addend of improved antiscoring properties.

2 tbl, 1 ex

FIELD: synthesis of lubricant oil additives.

SUBSTANCE: method for production of O-(2-ethyl-n-hexil)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid 1-(N,N-dimethylaminomethyl)-benzotriazole salt of general formula 2 is disclosed. 1-(N,N-dimethylaminomethyl)-benzotriazole is brought into reaction with equimolar amount of O-(2-ethyl-n-hexyl)-O-3,4,5-trithiatricyclo-dez-8-yl-methyl)-dithiophosphoric acid in toluene medium at 80-100°C for 2-4 h.

EFFECT: ash-free antiscoring lubricant oil additive operating under high pressure.

2 tbl, 1 ex

FIELD: organic chemistry, in particular new lubricating oil additive.

SUBSTANCE: 1-(N,N-dimethylaminomethyl)-benzotriazole is brought into reaction with equimolar amount of O-(n-butyl)-O-(2-ethyl-n-hexyl)-dithiophosphoric acid at 80-100°C for 2-4 h. Yield of finished product is 92-100 %.

EFFECT: corrosion-resistant additive with antioxidative, high antiscoring properties, compatible with base oil.

1 cl, 1 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula I where R1 is lower alkyl or C3-C7-cycloalkyl; X is C(O) or SO2; m equals 0 or 1; R2 is selected from a group consisting of lower alkyl, lower halogenalkyl, lower alkoxyalkyl, unsubstituted C3-C7-cycloalkyl, lower phenylalkyl, where phenyl is unsubstituted or mono- or disubstituted with lower alkyl, lower alkoxy, halogen or lower halogenalkyl, unsubstituted pyridyl or pyridyl which is mono- or disubstituted with lower alkyl, halogen or lower halogenalkyl, -NR3R4 or if X is C(O), R2 can also denote a lower alkoxy or lower alkoxyalkoxy, or if m equals 1, R2 can be unsubstituted phenyl or phenyl which is mono- or disubstituted with lower alkyl, lower alkoxy, halogen or lower halogenalkyl, , R3 is hydrogen or lower alkyl; R4 is selected from a group consisting of lower alkyl, C3-C7-pycloalkyl, C3-C7-cycloalkyl which is substituted with phenyl, lower C3-C7-cycloalkylalkyl, unsubstituted phenyl or phenyl which is mono- or disubstituted with lower alkyl, lower alkoxy, halogen or lower halogenalkyl, and lower phenylalkyl, where phenyl is unsubstituted or mono- or disubstituted with lower alkyl; or R3 and R4 together with the nitrogen atom to which they are bonded form a 4-, 5-, 6-, or 7-member heterocyclic ring system which optionally contains one more heteroatom selected from nitrogen, where the said heterocyclic ring system is unsubstituted or substituted with one, two or three groups independently selected from lower alkyl, halogen, halogenalkyl; and pharmaceutically acceptable salts of these compounds; except 2,2-dimethyl-N-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]propionamide. The invention also relates to a pharmaceutical composition for treating diseases which are associated with modulation of histamine H3 receptors based on formula I compounds.

EFFECT: new compounds which can be used to treat and/or prevent diseases associated with modulation of histamine H3 receptors are obtained and described.

21 cl, 105 ex, 2 tbl

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