Oxazole compound and pharmaceutical composition

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to oxazole compound represented by formula (1) and its pharmaceutically acceptable salts. In formula (1) R1 represents phenyl group, which can contain one or two substituents, selected from the following groups (1-1)-(1-11): (1-1) hydroxy groups, (1-2) unsubstituted or halogen-substituted lower alkoxy groups, (1-3) lower alkenyloxy-groups, (1-4) lower alkinyloxy groups, (1-5) cycloC3-8alkyl (lower) alkoxy groups, (1-6) cycloC3-8alkyloxy groups, (1-7) cycloC3-8alkenyloxy groups, (1-8) dihydroindenyloxy groups, (1-9) hydroxyl-(lower)ankoxy groups, (1-10) oxiranyl(lower)alkoxy groups, and (1-11) phenyl(lower)-alkoxy groups; R2 represents phenyl group or heterocyclyl group, selected from pyridine, pyrasine, isoquinoline, pyrrolidine, piperazine, morpholine, each of which can contain one or two substituents, selected from the following groups (2-1)-(2-10):(2-1) hydroxy groups, (2-2) unsubstituted or halogen-substituted lower alkoxy groups, (2-3) unsubstituted or halogen-substituted lower alkyl groups, (2-4) lower alkenyloxy groups, (2-5) halogen atoms, (2-6) lower alkanoyl groups, (2-7) lower alkylthio groups, (2-8) lower alkylsulphonyl groups, (2-9) oxo groups and (2-10) groups lower alkoxy-lower alkoxy; and W represents bivalent group represented by formula (i) or (ii): formula (i) -Y -A -, formula (ii) -Y2-C(=O)-, where A1 represents lower alkenylene group or lower alkylene group, which can contain one substitutent, selected from group, consisting from hydroxy group and lower alkoxicarbonyl group, Y1 represents simple bond, -C(=O)-, -C(=O)-N(R3)-, -N(R4)-C(=O)-, -S(O)m-NH- or -S(O)n-, where R3 and R4, each independently, represent a hydrogen atom or lower alkyl group, and m and n, each independently, represent integer, which has value 2, and Y represents pyperazine-diyl group, or bivalent group, represented by formula (iii) or (iv): formula (iii) -C (=O)-A2-N(R5)-, formula (iv) A3-N(R6)-, where A2 and A3, each independently, represent lower alkylene group, and R5 and R6, each independently, represent a hydrogen atom. Invention also relates to pharmaceutical composition, containing the invention compound as an active ingredient, to pharmaceutical composition for treatment or prevention of atopic dermatitis, which includes the invention compound, to application of the compound as medication, to application of the compound as phosphodiesterase 4 inhibitor and/or as inhibitor of production of tumour necrosis factor α and to method of treatment or prevention of diseases, mediated by phosphodiesterase 4 or mediated by tumour necrosis factor α, including introduction of efficient dose of the compound.

EFFECT: creation of pharmaceutical composition for treatment or prevention of diseases mediated by phosphodiesterase 4 or mediated by tumour necrosis factor, as well as for treatment or prevention of atopic dermatitis.

12 cl, 42 tbl, 486 ex

 

The technical field

The present invention relates to new compounds of oxazole and pharmaceutical compositions.

Background of the invention

Various connection oxazole were developed and described in documents WO 03/072102, WO 98/15274 etc. But connection oxazole according to the present invention is not disclosed in the literature.

It was reported on some compounds with specific inhibitory activity against phosphodiesterase 4 (PDE4). However, the known inhibitors of PDE4 has side effects, such as inducing vomiting, nausea, etc. and/or minus, as the lack of inhibitory activity against PDE4. Consequently, known PDE4 inhibitors are not used for clinical purposes as therapeutic agents.

Disclosure of invention

The aim of the present invention is the provision of compounds with inhibitory activity against PDE4 and without the above-mentioned problems of the prior art.

The authors of the present invention have conducted extensive studies to solve the above problems, and succeeded in the synthesis of compounds of oxazole new structure, compounds with high specificity and strong inhibitory activity against PDE4. Moreover, the authors of the present invention found Thu the connection oxazole able to exercise preventive and/or therapeutic effects against PDE-mediated diseases, in particular, such as atopic dermatitis, is based on their inhibitory activity against PDE4. Moreover, the authors found that the compound has a low ability to leak into the blood when percutaneous introduction and, thus, has a low systemic side effects.

The authors present invention also found that the connection oxazole able to manifest inhibitory effect against tumor necrosis factor α (TNF-α).

It is known that chronic inflammatory diseases, such as autoimmune diseases and allergic diseases, cytokines produced by immune cells are important mediators of inflammation, and among these cytokines, TNF-α, as is, plays a particularly important role. Therefore, the connection oxazole of the present invention is extremely effective for the treatment of TNF-α-mediated diseases.

The present invention was created as a result of further research based on the above discoveries.

The present invention provides a compound of oxazole, the pharmaceutical composition comprising the specified connection, use the specified connection, the method of treatment or prevention of disease and the way to obtain the specified connection, as described in paragraphs 1-14 below.

Paragraph 1. The connection on which Sasol, represented by formula (1)

where R1represents an aryl group which may contain one or more substituents selected from the following groups (1-1)to(1-11):

(1-1) a hydroxy-group,

(1-2) unsubstituted or halogen-substituted lower alkoxygroup,

(1-3) lower alkenylacyl,

(1-4) lower alkyloxy,

(1-5) ciclos3-8alkyl(lower)alkoxygroup,

(1-6) ciclos3-8alkyloxy,

(1-7) ciclos3-8alkenylacyl,

(1-8) dihydroindolone,

(1-9) hydroxy(lower)alkoxygroup,

(1-10) oxiranyl(lower)alkoxygroup,

(1-11) - protected hydroxy-group;

R2represents an aryl group or a heterocyclic group containing a nitrogen atom, each of which may contain one or more substituents selected from the following groups (2-1)to(2-10):

(2-1) a hydroxy-group,

(2-2) unsubstituted or galactomannan low alkoxygroup,

(2-3) unsubstituted or halogen-substituted lower alkyl group,

(2-4) of the lower alkenylacyl,

(2-5) the atoms of halogen,

(2-6) the lower alcoholnye group,

(2-7) of the lower allylthiourea,

(2-8) the lower alkylsulfonyl group,

(2-9) the carbonyl group and

(2-10) group, a lower alkoxy-lower alkoxy; and

W represents a divalent group of t is run by the formula (i) or (ii):

Formula (i) -Y1-A1-

Formula (ii) -Y2-C(=O)-

where A1represents the lowest alkenylamine group or lower alkylenes group which may contain one or more substituents selected from the group consisting of hydroxy-group and lower alkoxycarbonyl group,

Y1represents a simple bond, -C(=O)-, -C(=O)-N(R3)-, -N(R4)-C(=O)-, -S(O)m-NH - or-S(O)n-

where R3and R4each independently represent a hydrogen atom or a lower alkyl group, and m and n each independently represent an integer having a value of from 0 to 2, and

Y2represents piperazinyl group, or a divalent group represented by the formula (iii) or (iv):

Formula (iii) or (iv):

Formula (iii) -C(=O)-And2-N(R5)-

Formula (iv) And3-N(R6)-

where A2and A3, each independently, represent lower alkylenes group, and R5and R6each independently represent a hydrogen atom or a lower alkyl group;

or its salt.

Paragraph 2. Connection paragraph 1

in which R1represents a phenyl group which has 1 to 3 substituents selected from the following groups (1-2), (1-3), (1-4) and (1-5):

(1-2) unsubstituted or halogen-substituted lower alkoxygroup,

(1-3) lower alkenyl is a system of groups,

(1-4) lower alkyloxy and

(1-5) ciclos3-8alkyl(lower)alkoxygroup;

R2represents a phenyl group or pyridyloxy group, each of which may contain from 1 to 3 substituents selected from the group consisting of the following (2-2), (2-3), (2-4) and (2-5):

(2-2) unsubstituted or halogen-substituted lower alkoxygroup,

(2-3) unsubstituted or halogen-substituted lower alkyl group,

(2-4) of the lower alkenylacyl and

(2-5) the atoms of halogen;

W represents a divalent group represented by the formula (i):

Formula (i) -Y1-A1-

in which A1represents the lowest alkylenes group, and

Y1represents-C(=O)- or-C(=O)-N(R3)-

where R3represents a hydrogen atom.

Item 3. Connection point 2

in which R1represents a phenyl group containing two substituent selected from the following groups (1-2), (1-3), (1-4) and (1-5):

(1-2) unsubstituted or halogen-substituted lower alkoxygroup,

(1-3) lower alkenylacyl,

(1-4) lower alkyloxy and

(1-5) ciclos3-8alkyl(lower)alkoxygroup;

R2represents a phenyl group or pyridyloxy group, each of which may contain from 1 to 2 substituents, selected from the following groups (2-2), (2-3), (2-4) and (2-5):

(2-2) nezamedin the e or halogen-substituted lower alkoxygroup,

(2-3) unsubstituted or halogen-substituted lower alkyl group,

(2-4) of the lower alkenylacyl and

(2-5) halogen atoms; and

W represents a divalent group represented by the formula (i):

Formula (i) -Y1-A1-

in which A1represents the lowest alkylenes group, and Y1represents-C(=O)- or-C(=O)-N(R3)-, where R3represents a hydrogen atom.

Item 4. Connection on paragraph 3

in which R1represents a phenyl group substituted in the phenyl ring two lowest alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one halogen-substituted lower alkoxygroup, phenyl group, substituted phenyl group, a single lower alkoxygroup and one lower alkynylamino, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one lower alkynylamino, or phenyl group, substituted phenyl ring two halogen-substituted lower alkoxy is a group;

R2represents the lowest alkoxyphenyl group, lower altneratively group, halogen-substituted lower alkoxyphenyl group, lower alkylpyridinium group or a phenyl group substituted in the phenyl ring by one lower alkoxygroup and one halogen atom; and

W represents a divalent group represented by the formula (i):

Formula (i) -Y1-A1-

in which A1represents a C1-4alkylenes group, and

Y1represents-C(=O)- or-C(=O)-N(R3)-,

where R3represents a hydrogen atom.

Paragraph 5. The connection point 4

in which R1represents a phenyl group substituted in the phenyl ring two lowest alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one halogen-substituted lower alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one lower alkynylamino, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring is ne low halogen-substituted lower alkoxygroup and one lower alkynylamino, or phenyl group, substituted phenyl ring two halogen-substituted lower alkoxygroup;

R2represents the lowest alkoxyphenyl group, lower altneratively group, halogen-substituted lower alkoxyphenyl group, lower alkylpyridinium group or a phenyl group substituted in the phenyl ring by one lower alkoxygroup and one halogen atom; and

W represents a divalent group represented by the formula (i):

Formula (i) -Y1-A1-

in which A1represents a C1-4alkylenes group, and

Y1represents-C(=O)-.

Item 6. The connection point 4

in which R1represents a phenyl group substituted in the phenyl ring by one lower alkoxygroup and one halogen-substituted lower alkoxygroup, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, or a phenyl group substituted in the phenyl ring with one halogen-substituted lower alkoxygroup and one lower alkynylamino;

R2represents the lowest alkoxyphenyl group or lower alkylpyridinium group; and

W represents a divalent group represented by the formula (i):

Formula (i) -Y1A 1-

in which A1represents a C1-4alkylenes group, and

Y1represents-C(=O)-N(R3)-,

where R3represents a hydrogen atom.

Item 7. Pharmaceutical composition comprising the compound or salt according to any one of items 1-6 as an active ingredient and a pharmaceutically acceptable carrier.

Item 8. Pharmaceutical composition for treatment or prevention of diseases mediated by phosphodiesterase 4 and/or mediated by tumor necrosis factor α, where the composition includes a compound or salt according to any one of items 1-6.

Item 9. Pharmaceutical composition for treatment or prevention of atopic dermatitis, where the composition includes a compound or salt according to any one of items 1-6.

Paragraph 10. A method of obtaining a pharmaceutical composition, which comprises mixing the compound or salt according to any one of items 1-6 with a pharmaceutically acceptable carrier.

Paragraph 11. The use of compound or salt according to any one of items 1-6 as a medicine.

Item 12. The use of compound or salt according to any one of items 1-6 as an inhibitor of phosphodiesterase 4, and/or inhibiting the production of tumor necrosis factor α.

Paragraph 13. Method for the treatment or prevention of diseases mediated by phosphodiesterase 4 and/or indirect, factor the tumor necrosis α, the method includes introducing the compound or salt according to any one of items 1 to 6 human or animal.

Paragraph 14. The method of obtaining compounds of oxazole represented by the formula (1):

where R1, R2and W have the meanings given in paragraph l, or its salt, the method involves reacting a compound represented by the formula (2):

where R2and W have the meanings defined above, and X represents a halogen atom, or its salt with a compound represented by the formula (3):

where R1has the values defined above, or its salt.

In the formula (1) R1preferably represents a phenyl group. The phenyl group represented by R1preferably, contains from 1 to 3 and, more preferably, 2 substituent selected from the group comprising (1-2) unsubstituted or halogen-substituted lower alkoxygroup, (1-3) lower alkenylacyl, (1-4) lower alkyloxy and (1-5) ciclos3-8alkyl(lower)alkoxygroup.

In the formula (1) R2preferably represents a phenyl group or pyridyloxy group. Phenyl group or Peregrina group represented by R2preferably, contains from 1 to 3 substituents, and more preferably, 1 to replace the e l e C selected from the group comprising (2-2) unsubstituted or halogen-substituted lower alkoxygroup, (2-3) unsubstituted or halogen-substituted lower accelgroup, (2-4) of the lower alkenylacyl and (2-5) halogen atoms.

In the formula (1) W preferably represents a divalent group represented by the formula (i) -Y1-A1-. A1preferably represents a lower alkylenes group; Y1preferably represents-C(=O)- or-C(=O)-N(R3)-; and R3preferably represents a hydrogen atom.

Of the compounds of oxazole of the present invention preferred are those compounds which are represented by the formula (1A), and their salts, and most preferred are those compounds which are represented by the formula (1B) and their salts.

Formula (1A):

where R1represents a phenyl group containing two substituent selected from the following (1-2), (1-3), (1-4) and (1-5):

(1-2) unsubstituted or halogen-substituted lower alkoxygroup,

(1-3) lower alkenylacyl,

(1-4) lower alkyloxy and

(1-5) ciclos3-8alkyl(lower)alkoxygroup;

R2represents a phenyl group or pyridyloxy group, each of which may contain one or more substituents selected from the following groups (2-2), (2-), (2-4) and (2-5):

(2-2) unsubstituted or halogen-substituted lower alkoxygroup,

(2-3) unsubstituted or halogen-substituted lower accelgroup,

(2-4) of the lower alkenylacyl, and

(2-5) halogen atoms; and

W represents a divalent group represented by the formula (i):

Formula (i) -Y1-A1-,

in which A1represents the lowest alkylenes group, and

Y1represents-C(=O)- or-C(=O)-N(R3)-

where R3represents a hydrogen atom.

Formula (1B):

where R1represents a phenyl group substituted in the phenyl ring two lowest alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one halogen-substituted lower alkoxygroup, phenyl group, substituted phenyl group, a single lower alkoxygroup and one lower alkynylamino, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one cyclo C3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one lower alkynylamino, or f is niloy group, substituted in the phenyl ring two halogen-substituted lower alkoxygroup;

R2represents the lowest alkoxyphenyl group, lower altneratively group, halogen-substituted lower alkoxyphenyl group, lower alkylpyridinium group or a phenyl group substituted in the phenyl ring by one lower alkoxygroup and one halogen atom; and

W represents a divalent group represented by the formula (i):

Formula (i) -Y1-A1-,

in which A1represents a C1-4alkylenes group and

Y1represents-C(=O)- or-C(=O)-N(R3)-,

where R3represents a hydrogen atom.

The present invention is described in more detail below.

The compound represented by formula (1)

In the formula (1) R1represents an aryl group. The aryl group may contain from 1 to 3 and preferably 2 substituent selected from the group comprising (1-1) hydroxy-group, (1-2) unsubstituted or halogen-substituted lower alkoxygroup, (1-3) lower alkenylacyl, (1-4) lower alkyloxy, (1-5) ciclos3-8alkyl(lower)alkoxygroup, (1-6) ciclos3-8alkyloxy, (1-7) ciclos3-8alkenylacyl, (1-8) dihydroindolone, (1-9) hydroxy(lower)alkoxygroup, (1-10) oxiranyl(lower)alkoxygroup and (1-11) for imennye hydroxy-group.

In the formula (1) R2represents an aryl group or a heterocyclic group containing a nitrogen atom. Aryl group and heterocyclic group may contain from 1 to 3 substituents, and preferably 1 Deputy selected from the group comprising (2-1) hydroxy-group, (2-2) unsubstituted or halogen-substituted lower alkoxygroup, (2-3) unsubstituted or halogen-substituted lower alkyl group, (2-4) of the lower alkenylacyl, (2-5) halogen atoms, (2-6) lower alcoholnye groups (2-7) of the lower allylthiourea, (2-8) lower alkylsulfonyl group (2-9) the carbonyl group and (2-10) a lower alkoxy-lower alkoxygroup.

In the formula (1) W is a divalent group represented by the formula (i) or (ii):

Formula (i) -Y1-A1-

Formula (ii) -Y2-C(=O)-

where A1represents the lowest alkenylamine group or lower alkylenes group, which may contain from 1 to 3 and, preferably, 1 Deputy, selected from the group comprising hydroxy-group and lower alkoxycarbonyl group;

Y1represents a simple bond, -C(=O)-, -C(=O)-N(R3)-, -N(R4)-C(=O)-, -S(O)m-NH - or-S(O)n-,

where R3and R4each independently represent a hydrogen atom or a lower alkyl group, and m and n each independently represent an integer having a value is f from 0 to 2; and

Y2represents piperazinyl group or a divalent group represented by the formula (iii) or (iv):

Formula (iii) -C(=O)-And2-N(R5)-

Formula (iv) And3-N(R6)-

where A2and A3, each independently, represent lower alkylenes group, and

R5and R6each independently represent a hydrogen atom or a lower alkyl group.

Examples of aryl groups include phenyl, naphthyl, etc.

Examples of halogen atoms include fluorine, chlorine, bromine, iodine, etc

The lower alkyl groups are alkyl groups with straight or branched chain having 1-6 carbon atoms, and examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-ethylpropyl, n-pentyl, neopentyl, n-hexyl, isohexyl, 3-methylpentyl etc.

Unsubstituted or halogen-substituted lower altergroup represent an alkyl group with straight or branched chain having 1-6 carbon atoms, as defined above, or such alkyl groups substituted by 1 to 7 halogen atoms. Examples of such groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-ethylpropyl, n-pentyl, neopentyl, n-hexyl, isohexyl, 3-methylpentyl, vermeil, deformity, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, bromate is, dibromomethyl, dichloromethyl, 2-foretel, 2,2-dottorati, 2,2,2-triptorelin, pentafluoroethyl, 2-chloroethyl, 3,3,3-cryptochromes, heptafluoropropyl, heptafluoroisopropyl, 3-chloropropyl, 2-chloropropyl, 3-bromopropyl, 4,4,4-tripcomputer, 4,4,4,3,3-PENTACARBONYL, 4-chlorobutyl, 4-bromobutyl, 2-chlorobutyl, 5,5,5-tryptophanyl, 5-chloropentyl, 6,6,6-triptorelin, 6-chlorhex etc.

Low alkenylacyl represent the group consisting of oxygen atom, and C2-6alkenylphenol group with a straight or branched chain containing 1-3 double bonds. Low alkenylacyl have CIS - and transforms. More specific examples of such groups include vinyloxy, 1 propenyloxy, 2-propenyloxy, 1-methyl-1-propenyloxy, 2-methyl-1-propenyloxy, 2-methyl-2-propenyloxy, 2-propenyloxy, 2-butenyloxy, 1 butenyloxy, 3 butenyloxy, 2-pentyloxy, 1 pentyloxy, 3 pentyloxy, 4-pentyloxy, 1,3-butadienyl, 1,3-pentadienyl, 2-penten-4-yloxy, 3-methyl-2-butenyloxy, 2-hexenoate, 1 hexenoate, 5-hexenoate, 3 hexenoate, 4-hexenoate, 3,3-dimethyl-1-propenyloxy, 2-ethyl-1-propenyloxy, 1,3,5-hexatriene, 1,3-hexadienyl, 1,4-hexadienyl etc.

Examples of the lower alkyloxy include group consisting of oxygen atom, and C2-6etkinlik groups with straight or branched chain, containing from 1 to 3 triple bonds. More specific p is emery of such groups include itineracy, 2 propenyloxy, 2-butenyloxy, 3 butenyloxy, 1-methyl-2-propenyloxy, 2-pentyloxy, 2-hexyloxy etc.

Examples ciclos3-8alkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl etc.

Preferred examples of the lower alkoxygroup include C1-6alkoxygroup straight or branched chain. Specifically, such groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, 1 ethylpropoxy, n-pentox, neopentane, n-hexyloxy, isohexane, 3 methylpentane etc.

Examples ciclos3-8alkyl(lower)alkoxygroup include above the lower alkoxygroup, which contain from 1 to 3 and preferably 1 ciclos3-8the alkyl group above. More specific examples of such groups include cyclopropylmethoxy, cyclobutylmethyl, cyclohexylmethoxy, 2-cyclopropylmethoxy, 1 cyclobutylamine, cyclopentylamine, 3 cyclopentylpropionic, 4-cyclohexylmethoxy, 5-cycloheptylmethyl, 6-cyclooctylamine, 1,1-dimethyl-2-cyclohexylmethoxy, 2-methyl-3-cyclopropylmethoxy etc.

Examples ciclos3-8alkyloxy include cyclopropylamino, cyclobutylamine, cyclopentyloxy, cyclohexyloxy, cycloheptylamine, cyclooctylamine etc.

Examples ciclos3-8alkenylacyl include cycle is propenyloxy, cyclobutanone, Cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone etc.

Examples of dihydroergotoxine include 2,3-dihydroindol-1 yloxy, 2,3-dihydroindol-2-yloxy etc.

Examples of hydroxy(lower)alkoxygroup include low alkoxygroup (preferably, C1-6alkoxygroup straight or branched chain, containing from 1 to 5 and preferably 1 to 3 hydroxy groups. More specific examples of such groups include hydroxyethyloxy, 2-hydroxyethyloxy, 1 hydroxyethyloxy, 3 hydroxypropoxy, 2,3-dihydroxypropyl, 4-hydroxybutyrate, 3,4-dihydroxybutyl, 1,1-dimethyl-2-hydroxyethyloxy, 5-hydroxyethyloxy, 6-hydroxyhexyloxy, 3,3-dimethyl-3-hydroxypropoxy, 2-methyl-3-hydroxypropoxy, 2,3,4-trihydroxybutane, pelikokemuksia etc.

Examples oxiranyl(lower)alkoxygroup include C1-6alkoxygroup straight or branched chain containing 1 or 2 oxiranyl, such as, for example, oxiranylmethyl, 2-oxiranylmethyl, 1 oxalanilide, 3 oxyaliphatic, 4-oxiranylmethyl, 5-oxiranylmethyl, 6-oxiranylmethyl, 1,1-dimethyl-2-oxiranylmethyl, 2-methyl-3-oxyaliphatic etc.

Examples of protective groups for protecting hydroxy groups include lower alcoholnye and other acyl groups; the groups phenyl(lower)alkyl, unto the which may have one or more suitable substituents (for example, benzyl, phenetyl, 3-phenylpropyl, 4-methoxybenzyl, trityl etc.); tizanidine silyl group [for example, three(lower)alkylsilane group (for example, trimethylsilyl, tert-butyldimethylsilyl etc) and the like]; tetrahydropyranyl etc.

Examples of heterocyclic groups containing a nitrogen atom include pyrrolidinyl, imidazolidinyl, piperidyl, hexahydropyridine, piperazinil, activitiesunder, azepane, aziani, pyrrolyl, dihydropyrrole, imidazolyl, dihydroimidazole, triazolyl, dihydrotriazine, pyrazolyl, pyridyl and its N-oxides, dihydropyridin, pyrimidinyl, dihydropyrimidines, pyrazinyl, dihydropyrazine, pyridazinyl, tetrazolyl, indolyl, isoindolyl, indolinyl, isoindolyl, hexahydroquinoline, benzoimidazolyl, hinely, ethanolic, indazoles, hintline, dihydroquinazolines, benzotriazolyl, carbazolyl, oxazolyl, isooxazolyl, oxadiazolyl, oxazolidinyl, isooxazolyl, morpholinylmethyl, dihydroisoxazole, benzoxazines, dihydroisoxazole, benzoxazolyl, benzoxadiazole, thiazolyl, dihydrothiazolo, isothiazolin, thiadiazolyl, dihydrothiazine, diazolidinyl, benzothiazolyl, benzothiadiazole etc.

Unsubstituted or halogen-substituted lower alkoxygroup are alkoxygroup straight or branched chain, containing from 1 to 6 atoms ug is erode, or such alkoxygroup, substituted by 1 to 7 halogen atoms. Examples of such groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, 1 ethylpropoxy, n-pentox, neopentane, n-hexyloxy, isohexane, 3 methylpentane, formatosi, deformedarse, triptoreline, chloromethoxy, dichloromethoxy, trichlormethane, bromoethoxy, dibromethane, dichloromethoxy, 2-floratone, 2,2-diflorasone, 2,2,2-triptoreline, pentaborate, 2-chloroethoxy, 3,3,3-cryptocracy, heptafluoropropoxy, heptafluoroisopropoxy, 3 chloropropoxy, 2-chloropropoxy, 3 bromopropane, 4,4,4-triptoreline, 4,4,4,3,3-pentafluorobutane, 4-chloroethoxy, 4-bromoethoxy, 2-chloroethoxy, 5,5,5-triterpenes, 5-chlorphenoxy, 6,6,6-triptoreline, 6-chlorhexidine etc.

Examples of the lower alkanoyl groups include formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbamoyl, hexanoyl and other C1-6alcoholnye group with a straight or branched chain.

Examples of the lower alkylthio include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, tert-butylthio, n-pentylthio, n-hexylthio and other C1-6ancilliary straight or branched chain.

Preferred examples of the lower alkylsulfonyl groups include C1-6alkylsulfonyl group with straight or branched C the drink. More specific examples of such groups include methylsulphonyl, ethylsulfonyl, n-propylsulfonyl, isopropylphenyl, n-butylsulfonyl, isobutylamine, tert-butylsulfonyl, second-butylsulfonyl, n-peterculter, isopentylamine, neopentylene, n-hexylsilane, isohexanol, 3-methylphenylsulfonyl etc.

Lower alkenylamine groups include, for example, vinylidene, propylene, bouteillan and other C2-6alchemistroy straight or branched chain, containing from 1 to 3 double bonds.

Preferred examples of the lower alkoxycarbonyl groups include the group consisting of C1-6alkoxygroup straight or branched chain and carbonyl groups. Specific examples of such groups include methoxycarbonyl, etoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxide, tert-butoxycarbonyl, second-butoxycarbonyl, n-phenoxycarbonyl, neopentecostal, n-hexyloxymethyl, isohexadecane, 3-methylphenoxyacetic etc.

Lower alkylene groups include, for example, ethylene, trimethylene, 2-metallisation, 2,2-dimethyltrimethylene, 1-metallisation, METROTILE, utilitiles, tetramethylene, pentamethylene, hexamethylene and other C1-6alkylene group with a straight or branched chain.

Examples of groups lower Alcock and lower alkoxy include alkoxyalkyl, in which each of the two alkoxyamines, independently, represents a C1-6alkoxygroup straight or branched chain. Specific examples of such groups include methoxyethoxy, 2-methoxyethoxy, 3 methoxypropane, 4-methoxybutyl, 5-methoxyphenoxy, 6-methoxyacetate, ethoxyethoxy, 2-ethoxyethoxy, n-propoxymethyl, isopropoxyphenoxy, n-butoxyethoxy etc.

Examples of C1-4alkilinity groups include ethylene, trimethylene, 2-metallisation, 2,2-dimethyltrimethylene, 1-metallisation, METROTILE, utilitiles, tetramethylene and other C1-4alkylene group with a straight or branched chain.

Methods for obtaining compounds represented by formula (1)

Connection oxazole represented by the formula (1)may be obtained in various ways, one example of which is presented in the reaction scheme 1.

The scheme of reactions 1

where R1, R2and W have the meanings defined in formula (1), and X represents a halogen atom.

The compound (1) produced by interaction of the compound (2) with compound (3).

The interaction of the compound (2) with compound (3) is usually carried out in a suitable solvent. You can use various known solvents, provided that they do not inhibit the reaction. Examples of such solvents include dim telharmonic, dimethyl sulfoxide, acetonitrile and other aprotic polar solvents; acetone, methyl ethyl ketone, and other ketone solvents; benzene, toluene, xylene, tetralin, liquid paraffin and other hydrocarbon solvents; methanol, ethanol, isopropanol, n-butanol, tert-butanol and other alcohol solvents; tetrahydrofuran, dioxane, DIPROPYLENE ether, diethyl ether, dimethoxyethane, diglyme and other ethereal solvents; ethyl acetate, methyl acetate and other ester solvents; mixtures thereof; etc These solvents may contain water.

The ratio of the compounds (3) to the compound (2) is usually from 0.5 to 5 mol, and preferably from 0.5 to 3 mol, per mol of compound (2).

The interaction of the compound (2) with compound (3) is usually carried out under continuous stirring at a temperature of from -20 to 200°C and preferably from 0 to 150°C, during the time from 30 minutes to 60 hours, and preferably from 1 to 30 hours.

The compound (3)used as starting substances, is a readily available well-known compound. Connection (2) covers the new connection, and method for producing such a compound is described below (reaction scheme 9).

Of the compounds of oxazole represented by the formula (1), compounds in which W represents a divalent group represented by the formula-Y1-A1-in kotoroya 1represents-C(=O)-N(R3)- (hereinafter designated as compound (1a)”), can be obtained, for example, shown in reaction scheme 2.

The scheme of reactions 2

where R1, R2, R3and A1have the meanings defined in formula (1).

The compound (1a) is produced by interaction of the compound (4) or its reactive derivative at carboxypropyl with compound (5) or its reactive derivative at the amino - or aminogroups.

Preferred examples of the reactive derivative of compound (4) include acid halides, acid anhydrides, activated amides, activated esters, etc. Preferred examples of the reactive derivative include acid anhydrides, azides acids; dialkylphosphorous acid, phenylphosphino acid, diphenylphosphoryl acid, dibenzylamino acid, halides of phosphoric acid and other substituted phosphoric acid, dialkylphosphorous acid, sulfurous acid, Miserlou acid, sulfuric acid, methanesulfonate acid and other sulfonic acid, acetic acid, propionic acid, butyric acid, somaclonal acid, Pavlinov acid, pentane acid, isopentane acid, 2-atillasoy acid, trichloroacetic acid and the other is e aliphatic carboxylic acid, and mixed acid anhydrides with acids, such as benzoic acid or other aromatic acids; symmetric acid anhydrides; activated amide with imidazole, 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole; cinematology ether, methoxymethyl ether, dimethylaminomethylene ether, vinyl ether, propargilovyh ether, para-nitrophenyloctyl ether, 2,4-dinitrophenoxy ether, trichloranisole ether, pentachlorphenol ether, methylphenylene ether and other activated esters, esters with N,N-dimethylhydroxylamine, 1-hydroxy-2-(1H)-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole and other N-hydroxidealuminum; etc. These reactive derivatives can be selected, if so desired, in accordance with the type of connection (4).

When using the compound (4) in the form of free acid or its salt in the above reaction, is preferred as the reaction in the presence of the agent(s) condensation. You can use a wide range of condensing agents known in this field, including, for example, N,N'-dicyclohexylcarbodiimide; N-cyclohexyl-N'-morpholinobutyrophenone; N-cyclohexyl-N'-(4-diethylaminoethoxy)carbodiimide; N,N'-diethylcarbamoyl; N,N'-diisopropylcarbodiimide; N-ethyl-N'-(3-dim is calaminaris)carbodiimide and their hydrochloride; N,N'-carbonylbis(2-Mei); pentamethylene-N-cyclohexylamine; diphenylethan-N-cyclohexylamine; ethoxyacetylene, 1-alkoxy-1-chlorethylene; trialkylphosphine; etiloleat; isopropylpalmitate; phosphoroxychloride (phosphorylchloride); trichloride phosphorus; phosphoryldiesterase; thionyl chloride; oxacillin; ethylchloride, isopropylcarbamate, and other lower alkylsulfonate; triphenylphosphine; salt of 2-ethyl-7-hydroxybenzotriazole; inner salts of 2-ethyl-5-(meta-sulfophenyl)Toxicological; hexaphosphoric acid benzotriazol-1 yloxy-Tris(dimethylamino)phosphonium; 1-(para-chlorobenzenesulfonate)-6-chloro-1H-benzotriazol; the so-called reagents, Vilsmeier obtained by the interaction of N,N-dimethylformamide with thionyl chloride, phosgene, trichloromethylcarbonate, phosphorus oxychloride, etc.; etc. Most preferred is the reaction in the presence of such agent(s) condensation and active agent(s) of esterification, as the N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole, or the like

Preferred examples of the reactive derivative of compound (5) include the tautomers Schiff bases imino - or raminosoa type, obtained by the interaction of the compound (5) with carbonyl compounds such as aldehydes, ketones, etc.; silyl derivative obtained is haunted by the interaction of the compound (5) with silyl compounds, such as bis(trimethylsilyl)ndimethylacetamide, mono(trimethylsilyl)acetamide", she bis(trimethylsilyl)urea, etc.; derivatives obtained by the interaction of the compound (5) with trichloride phosphorus, phosgene, etc; etc.

Communication is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, diglyme, and other ether solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide and other aprotic polar solvents; n-pentane, n-hexane, n-heptane, cyclohexane, and other hydrocarbon solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; other organic solvents; and including their mixed solvents.

The reaction can be performed in the presence of base(s). You can use a wide range of inorganic and organic bases. Inorganic bases include, for example, alkali metals (e.g. sodium, potassium, etc), carbonates of alkali metals (for example, the Hydra is lithium carbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium etc) and hydrides of alkali metals (e.g. sodium hydride, potassium hydride, etc.). Organic bases include, for example, trialkylamine [e.g., trimethylamine, triethylamine, n-ethyldiethanolamine etc.], pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, n-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. If such grounds are liquid, they can also be used as solvents.

Such grounds can be used separately or in combination.

The amount of base(s) is usually from 0.1 to 10 mol and preferably from 0.1 to 3 mol, per mol of compound (4).

The ratio of the compound (4) to the compound (5) in the reaction scheme 1 is usually at least 1 and preferably from about 1 to about 5 moles of the first mole of the latter.

The reaction temperature is not limited, and the reaction is usually carried out under cooling, at to the room temperature or when heated. Preferred is the reaction takes place at a temperature ranging from room temperature to 100°C for a time from 30 minutes to 30 hours and preferably for a time from 30 minutes to 5 hours.

In the above reaction, the compound (4)used as the starting material is a readily available well-known compound. The compound (5) includes new connections. The method of obtaining the compound (5) described below (reaction scheme 10).

Of the compounds of oxazole represented by the formula (1), compounds in which W represents a divalent group represented by the formula-Y1-A1-, in which Y1represents-C(=O)- and A1represents the lowest alkylenes group containing one lower alkoxycarbonyl group (hereinafter designated as compound (1b)”), can be obtained, for example, using the method presented in reaction scheme 3.

The reaction scheme 3

where R1and R2defined in the formula (1), R7and R8each independently represent a lower alkyl group and A1arepresents a C1-5alkylenes group.

-COOR8the group in the formula (1b) has the same value as the lowest alkoxycarbonyl group, defined as Deputy A1in the formula (1). Lower alkyl group, who provided R 7can have the same meaning as the lower alkyl group defined above.

Examples of C1-5alkalinous group, represented as A1ainclude ethylene, trimethylene, 2-metallisation, 2,2-dimethyltrimethylene, 1-metallisation, METROTILE, utilitiles, tetramethylene, pentamethylene and other C1-5alkylene group with a straight or branched chain.

The compound (1b) is produced by the interaction of the compound (6) with compound (7).

The reaction is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, diglyme and other ethereal solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, N-organic and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; and including their mixed solvents.

Usually, the reaction can be performed in the presence of a suitable base(s). You can use mnozhestvennosti inorganic and organic bases. Inorganic bases include, for example, alkali metals (e.g. lithium, sodium, potassium etc), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium tert-piperonyl potassium tert-piperonyl sodium tert-pentoxide, sodium and so on), melodramatically (for example, sodium hydride, potassium hydride, etc. and the like, Organic bases include, for example, trialkylamine (for example, trimethylamine, triethylamine, N-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. When such grounds are liquid, they can also be used as solvents. Such grounds can be used separately or in combination.

The amount of base(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (6).

The ratio of compounds (6) to connect the s (7) is usually, at least 1 mol and, preferably, from about 1 to about 5 moles of the first mole of the latter.

The reaction temperature is not limited, and usually the reaction can be performed under cooling, at room temperature or when heated. A suitable implementation is the reaction at a temperature ranging from room temperature to 150°C for a time from 30 minutes to 60 hours, and preferably from 1 to 30 minutes.

The compound (6)used as the starting material in the above reaction is readily available known connection. Compound (7) covers the new connection. The method of obtaining the compound (7) described below (reaction scheme 11).

Of the compounds of oxazole represented by the formula (1), compounds in which W represents a divalent group represented by-Y1-A1-where A1represents the lowest alkylenes group (hereinafter designated as compound (1d)”), obtained from the corresponding compounds in which m1represents the lowest alkylenes group that contains the lowest alkoxycarbonyl group(s) (hereinafter designated as compound (1c)”), the method shown in the reaction scheme 4.

The reaction scheme 4

where R1, R2and Y1defined in the formula (1), A1brepresents the lowest alkylenes group, terzidou lower alkoxycarbonyl group(s), and A1crepresents the lowest alkylenes group.

The compound (1d) receive, by subjecting the compound (1c) hydrolysis-decarboxylation.

The reaction is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, diglyme and other ethereal solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, N-organic, and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; and including their mixed solvents.

Hydrolysis-decarboxylation of compound (1c) is usually carried out in acidic conditions. For example, acid is added to a suspension or solution of the compound (1c) in a suitable solvent, and the resulting mixture is stirred at a temperature of 0 to 120°C for the implementation of the hydrolysis-decarboxylation.

Examples suitable for use acids include triperoxonane acid, acetic acid and other institutions the institutions acid, hydrochloric acid, bromic acid, Hydrobromic acid, sulfuric acid and other inorganic acids, etc. From such organic acids organic acids can also be used as solvents for the reaction.

The amount of acid(acid) is usually from 0.5 to 30 mol, and preferably from 0.5 to 10 mol, per mol of compound (1c).

The reaction temperature is usually from 0 to 120°C and preferably from room temperature to 110°C. the reaction Time is usually from 30 minutes to 24 hours, preferably from 30 minutes to 12 hours and more preferably from 1 to 8 hours.

Of the compounds of oxazole represented by the Formula (1), compounds in which R1represents a phenyl group substituted in the phenyl ring hydroxy-group(s) (hereinafter designated as compound (1f)”) is obtained from the corresponding compounds where R1represents a phenyl group, substituted phenyl ring is protected by a hydroxy-group(s) (hereinafter designated as compound (1E)”), the method shown in the reaction scheme 5.

The reaction scheme 5

where R2and W are defined in the formula (1); R9represents a protected hydroxy-group; R10represents the same group as the substituent (1-2), (1-3), (1-4), (1-5), (1-6), (1-7), (1-8), (1-9) and (1-10) aryl groups which, represented as R1in the formula (1); m has a value from 1 to 5; q has a value from 0 to 4; m for groups of R9may be the same or different from each other; and q for groups of R10may be the same or different from each other; provided that m+q ≤5.

The compound (1f) can be obtained by subjecting the compound (1e) the elimination reaction of the hydroxy-protective group(s).

The elimination reaction can be performed by hydrolysis, hydrogenolysis or other conventional methods.

The reaction is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, diglyme and other ethereal solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, N-organic and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; and other organic solvents.

(i) Hydrolysis:

The hydrolysis is preferably carried out in the presence of a base(s) or acid(acids (including acid Lewis).

You can use a variety of known inorganic and organic bases. Preferred examples of inorganic bases include alkali metals (e.g. sodium, potassium etc), alkaline earth metals (e.g. magnesium, calcium, etc.), hydroxides, carbonates and bicarbonates of these metals, etc. Preferred examples of organic bases include trialkylamine (for example, trimethylamine, triethylamine, etc.), picoline, 1,5-diazabicyclo[4.3.0]non-5-ene, etc.

You can use a variety of known inorganic and organic acids. Preferred organic acids include, for example, formic acid, acetic acid, propionic acid and other fatty acid; trichloroacetic acid, triperoxonane acid and other trigalogenmetany acid; and the like, the Preferred inorganic acids include, for example, hydrochloric acid, Hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide, etc. are Examples of Lewis acids include ether complexes of boron TRIFLUORIDE, tribromide boron, aluminum chloride, ferric chloride, etc.

When used trigalogenmetany acid or a Lewis acid, preferably effecting hydrolysis in the presence of acceptor cations (e.g. anisole, phenol and so on).

The amount of base(s) or acid(the slot) is not limited. Assuming that it represents the amount required for hydrolysis.

The reaction temperature is usually from 0 to 120°C, preferably from room temperature to 100°C and more preferably from room temperature to 80°C. the reaction Time is usually from 30 minutes to 24 hours, preferably from 30 minutes to 12 hours and more preferably from 1 to 8 hours.

(ii) the Hydrogenolysis:

The hydrogenolysis can be accomplished by many known methods, including, for example, chemical reduction, catalytic reduction, etc.

Examples of suitable reducing agents for chemical recovery include hydrides (for example, modesty hydrogen, hydrogen sulfide, sociallyengaged, sodium borohydride, cyanoborohydride sodium and so on); and combinations of metals (e.g. tin, zinc, iron, etc. or compounds of metals (e.g. chromium chloride, chromium acetate, etc.) with organic or inorganic acids (e.g. formic acid, acetic acid, propionic acid, triperoxonane acid, para-toluensulfonate acid, hydrochloric acid, Hydrobromic acid, etc.).

Examples of suitable catalysts for catalytic reduction include platinum catalysts (e.g. platinum plate, spongy platinum, platinum black, colloidal PL is Tina, the platinum oxide, platinum wire, etc), palladium catalysts (e.g. spongy palladium, palladium black, palladium oxide, palladium-on-carbon, palladium/barium sulfate, palladium/barium carbonate, etc.), Nickel catalysts (e.g., the recovered Nickel, Nickel oxide, Raney Nickel, etc.), cobalt catalysts (e.g., the recovered cobalt, Raney cobalt, etc.), catalysts based on iron (e.g., reduced iron and the like), etc.

When such acids used for chemical recovery, are liquid, they can also be used as solvents.

The amount of reducing agent for chemical recovery and catalyst for catalytic reduction is not limited, and it may be a commonly used number.

The reaction temperature is usually from 0 to 120°C, preferably from room temperature to 100°C and more preferably from room temperature to 80°C. the reaction Time is usually from 30 minutes to 24 hours, preferably from 30 minutes to 10 hours and more preferably 30 minutes to 4 hours.

Of the compounds of oxazole represented by the formula (1), compounds in which R1represents a phenyl group substituted in the phenyl ring of R11O-group(group) (hereinafter designated as compound (1g)”), get the C of compound (1f), the method shown in reaction scheme 6.

The scheme of reactions 6

where R2and W are defined in the formula (1); R10, m and q are defined above; X1represents a halogen atom or a group which is subjected to the same substitution reaction as halogen atom; R11O represents the same group as the substituent (1-2), (1-3), (1-4), (1-5), (1-6), (1-7), (1-8), (1-9) and (1-10) aryl group represented by R1in the formula (1); and m groups R11O may be the same or different from each other.

In the compound (8) halogen atom represented by X1represents a fluorine atom, chlorine atom, bromine atom or iodine atom.

Examples of the group which is subject to the same substitution reaction as the halogen atom denoted as X1include low alkanesulfonyl, arylsulfonate, Arakishvili etc.

Specific examples of the lower alkanesulphonic include methanesulfonate, econsultancy, isopropanolamine, n-propanesulfonate, n-butanesulfonate, tert-butanesulfonate, n-pentanesulfonate, n-hexanesulfonate and other C1-6alkanolammonium straight or branched chain, etc.

Arylsulfonate include, for example, phenylsulfonyl, naftiliaki etc Phenyl ring such arylsulfonate may contain, for example, from 1 to 3 substituents selected from the group comprising C1-6alkyl group with straight or branched chain, C1-6alkoxygroup straight or branched chain, nitro and halogen atoms. Specific examples of such arylsulfonate include phenylsulfonyl, 4-methylphenylsulfonyl, 2-methylphenylsulfonyl, 4-nitrophenylacetylene, 4-methoxyphenylalanine, 2-nitrophenylacetylene, 3 chlorophenylsulfonyl etc. Specific examples of afterselefdierbbbp include α-naftiliaki, β-naftiliaki etc.

Arakishvili include, for example, phenyl-substituted C1-6alkylsulfonates straight or branched chain, which may contain, in the phenyl ring, 1 to 3 substituents selected from the group comprising C1-6alkyl group with straight or branched chain, C1-6alkoxygroup straight or branched chain, nitro and halogen atoms; naphthyl-substituted C1-6alkylsulfonates straight or branched chain; etc. Specific examples of the above phenyl-substituted alkylsulfonates include benzylmalonate, 2-phenylethylperoxo, 4-phenylmethylsulfonyl, 2-methylbenzenesulfonate, 4-methoxybenzenesulfonyl, 4-nitrobenzenesulfonate, 3-Harbin is ylsulphonyl etc. Specific examples of the above naphthyl-substituted alkylsulfonates include α-naphthylenediisocyanate, β-naphthalenyloxy etc.

The compound (1g) is produced by the interaction of the compound (1f) with the compound (8) or by reacting the compound (1f) with the compound (8').

The interaction of the compound (1f) with the compound (8) described below.

The interaction of the compound (1f) with the compound (8) is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, diglyme, and other ether solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; including their mixed solvents; etc

The interaction of the compound (1f) with the compound (8) is usually carried out in the presence of a base(s). Bases that can be used include known inorganic and organic basis of the Oia. Inorganic bases include, for example, alkali metals (e.g. sodium, potassium, etc.), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium etc), hydrides of alkali metals (for example, sodium hydride, potassium hydride, etc. and the like, Organic bases include, for example, trialkylamine (for example, trimethylamine, triethylamine, N-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. When such grounds are liquid, they are also can be used as solvents. Such grounds can be used separately or in combination.

The amount of base(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (1f).

When carrying out the above reaction in the reaction system, you can add the iodides of alkali meta is fishing, such as potassium iodide, sodium iodide, etc. as reaction accelerators, if necessary.

The ratio of the compound (1f) into the compound (8) is generally at least 1 mol, and preferably from about 1 to about 5 moles of the latter per mole of the first.

The reaction temperature is not limited, and usually the reaction can be performed under cooling, at room temperature or when heated. A suitable implementation is the reaction at a temperature of about room temperature in a period of time from 1 to 30 hours.

The following describes the interaction of the compound (1f) with the compound (8').

The interaction of the compound (1f) with the compound (8') is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, diglyme, and other ether solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide and other aprotic polar solvents; benzene, toluene, xylene, and other aromatic hydrocarbon solvents; methylene chloride, telengard and other halogenated hydrocarbon RA the founders; other organic solvents; including their mixed solvents; etc

The reaction is usually carried out in the presence of dialkyldithiocarbamate(s), such as diisopropylcarbodiimide, diethylazodicarboxylate etc. and phosphine ligand(s), such as triphenylphosphine, three(n-butyl)phosphine, etc. the Number of dialkyldithiocarbamate(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (1f). The amount of phosphine ligand(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (1f).

The interaction of the compound (1f) with the compound (8') can be performed in the presence of a suitable base(s). You can use a variety of known inorganic and organic bases. Inorganic bases include, for example, alkali metals (e.g. sodium, potassium, etc.), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium etc), hydrides of alkali metal is (for example, sodium hydride, potassium hydride, etc. and the like, Organic bases include, for example, trialkylamine (for example, trimethylamine, triethylamine, N-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. When such grounds are liquid, they are also can be used as solvents. Such grounds can be used separately or in combination.

The amount of base(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (1f).

The ratio of the compound (1f) into the compound (8') is generally at least 1 mol, and preferably from about 1 to about 5 moles of the latter per mole of the first.

The reaction temperature is not limited, and usually the reaction can be performed under cooling, at room temperature or when heated. A suitable implementation is the reaction at a temperature of about room temperature in a period of time from 1 to 30 hours.

Compounds (8) and (8'), used as starting materials in the above reaction are readily available known compounds.

Of the compounds of oxazole represented by the formula (1), compounds in which W represents a divalent g is the SCP, presents-Y1-A1-where Y1represents-C(=O) and A1represents the lowest alkenylamine group (hereinafter designated as compound (1h)”), can be obtained for example, by the method shown in reaction scheme 7.

The scheme of reactions 7

where R1and R2defined in the formula (1), and A1drepresents a C2-4alkynylamino group, C1-4alkylenes group or a simple bond.

Each of the C2-4alkenyl groups and C1-4alkilinity groups may be straight or branched chain. -CH=CH-A1d- corresponds to the lowest alkynylamino group, represented by A1in the formula (1).

The compound (1h) is produced by the interaction of the compound (9) with compound (10).

The reaction is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, diglyme and other ethereal solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, N-organic and other aprotic polar is haunted solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; including their mixed solvents; etc

The reaction can be performed in the presence of base(s). You can use a variety of known inorganic and organic bases. Inorganic bases include, for example, alkali metals (e.g. lithium, sodium, potassium etc), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium tert-piperonyl potassium tert-piperonyl sodium etc), hydrides of alkali metals (e.g. sodium hydride, potassium hydride, etc. and the like, Organic bases include, for example, trialkylamine (for example, trimethylamine, triethylamine, N-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU and so When such grounds represents the t of a liquid, they can also be used as solvents. Such grounds can be used separately or in combination.

The amount of base(s) is usually from 0.5 to 10 mol, and preferably from 0.5 to 6 mol, per mol of compound (9).

The ratio of the compounds (9) to the compound (10) is generally at least 1 mol and, preferably, from about 1 to about 5 mol, mol first.

The reaction temperature is not limited, and usually the reaction can be performed under cooling, at room temperature or when heated. A suitable implementation is the reaction at a temperature ranging from room temperature to 150°C, during the time from 30 minutes to 60 hours, and preferably from 1 to 30 hours.

Compound (9)used as the starting material in the above reaction, is easily accessible by a known connection. The compound (10)used as the starting material in the above reaction, can be obtained by the method shown in reaction scheme 12.

Of the compounds of oxazole represented by the formula (1), compounds in which W represents a divalent group represented by-Y1-A1-where A1represents the lowest alkylenes group (hereinafter designated as compound (1j)”), can be obtained from compounds in which m1represents Nissho alkenylamine group (hereinafter designated as compound (1i)”), the method shown in reaction scheme 8.

The scheme of reactions 8

where R1and R2defined in the formula (1), Y1defined above, A1erepresents the lowest alkynylamino group, and A1frepresents the lowest alkylenes group.

The compound (1j) receive, by subjecting the compound (1i) to hydrogenolysis.

The reaction is carried out in the same reaction conditions as the reaction conditions shown in the reaction scheme 5 for the hydrogenolysis of compound (1e), to obtain the compound (1f). Therefore, in the above reaction, you can use the same reagent(s) and reaction conditions (e.g. solvent, reaction temperature and so on), as used in the hydrogenolysis shown in the reaction scheme 5.

The reaction scheme 9

where R2and W are defined in the formula (1), and X is defined above.

The halogenation reaction of the compound (11) is carried out in a suitable solvent in the presence of a halogenation agent. The halogenation agents that can be used include, for example, Br2, Cl2and other molecules of halogen; chloride of iodine, sulfurylchloride, bromide, copper, and other copper compounds N-bromosuccinimide, N-chlorosuccinimide and other N-halogenating etc. Suitable solvents include, for example, dichloromethane, dichloroethane, chloroform, shall Erhard carbon and other halogenated hydrocarbons; acetic acid, propionic acid and other fatty acids; carbon disulphide; and so the Number of halogenation agent is usually from 1 to 10 mol and preferably from 1 to 5 mol, per mol of compound (11). The reaction is usually carried out at a temperature from 0°C to the boiling point of the solvent and preferably from about 0 to about 100°C, for a time from about 5 minutes to about 20 hours.

Of the compounds (5) for use as starting compounds, the compounds in which R3represents a hydrogen atom (hereinafter designated as compound (5a)”), produced by the method shown in the reaction scheme 10.

The reaction scheme 10

where R1and A1defined in the formula (1), X2and X3each independently represent a halogen atom or a group which is subjected to the same substitution reaction as the halogen atom as described above, and M represents an alkali metal.

Examples of the alkali metal represented as M include sodium, potassium, etc.

The compound (14) are obtained by reacting the compound (12) compound (13).

The interaction of the compound (12) compound (13) is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isoprop the Nol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, diglyme and other ethereal solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, N-organic and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; and other organic solvents; etc

The ratio of the compound (12) compound (13) is generally at least 1 mol and, preferably, from about 1 to about 5 moles of the latter per mole of the former. The interaction of the compound (12) compound (13) is carried out with continuous stirring, usually at a temperature ranging from room temperature to 200°C and preferably from room temperature to 150°C, usually in a period of time from 30 minutes to 60 hours, and preferably from 1 to 30 hours.

Compound (16) obtained by interaction of the compound (15) with compound (14).

The interaction of the compound (15) with compound (14) is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin is, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, diglyme, and other ether solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; mixtures thereof; etc

When conducting connection (15) with compound (14) in the reaction system, you can add the iodides of alkali metals, such as potassium iodide, sodium iodide, etc. as reaction accelerators, if necessary.

The ratio of the compounds (15) to the compound (14) is generally at least 1 mol and, preferably, from about 1 to about 5 moles of the latter per mole of the first.

The reaction temperature of the compound (15) with compound (14) is not limited, and usually the reaction can be performed under cooling, at room temperature or when heated. A suitable implementation is the reaction at a temperature ranging from room temperature to 100°C, during the time from 1 to 60 hours and, preferably, from 1 to 30 hours.

In the reaction of compound (15) with compound (14) phthalimide can be used instead of the compound (15), and reacciona to perform in the presence of base(s). You can use a variety of known inorganic and organic bases. Examples of inorganic bases include alkali metal (e.g. lithium, sodium, potassium etc), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium tert-piperonyl potassium tert-piperonyl sodium etc), hydrides of alkali metals (e.g. sodium hydride, potassium hydride, etc. and the like, Organic bases include, for example, trialkylamine (for example, trimethylamine, triethylamine, N-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and etc

The amount of base(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (14).

The compound (5a) is produced by the interaction of the compound (16) with compound (17).

The interaction of the compound (16) with compound (17) is usually the OCA is estlat in a known solvent, which does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, diglyme, and other ether solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; mixtures thereof; etc

The ratio of the compound (16) to the compound (17) is generally at least 1 mol and, preferably, from about 1 to about 5 moles of the latter per mole of the first.

The reaction temperature of the compound (16) with compound (17) is not limited, and usually the reaction can be performed under cooling, at room temperature or when heated.

A suitable implementation is the reaction at a temperature of about room temperature in a period of time from 1 to 30 hours.

The reaction scheme 11

where R1defined in the formula (1); R8and A1adefined above; X4represents a halogen atom or a group which is subjected to the same substitution reaction, as the halogen atom, as above; and R12represents a lower alkyl group.

The compound (20) obtained by interaction of the compound (18) with compound (19).

The interaction of the compound (18) with compound (19) is usually carried out in a known solvent that does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, dimethoxyethane, diglyme and other ethereal solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, N-organic and other aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; mixtures thereof; etc

The interaction of the compound (18) with compound (19) is usually carried out in the presence of a suitable base(s). You can use a variety of known inorganic and organic bases. Inorganic bases include, for example, alkali metals (e.g. lithium, sodium, potassium etc), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, hydroc rbonate potassium etc), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium tert-piperonyl potassium tert-piperonyl sodium etc), hydrides of alkali metals (e.g. sodium hydride, potassium hydride, etc. and the like, Organic bases include, for example, trialkylamine (for example, trimethylamine, triethylamine, n-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. When such grounds are liquid, they can also be used as solvents.

Such grounds can be used separately or in combination.

The amount of base(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (18).

The ratio of the compound (18) to the compound (19) in the reaction scheme 11 is generally at least 1 mol and, preferably, from about 1 to about 5 moles of the latter per mole of the first.

The reaction temperature is not limited, and usually the reaction can be carried out during cooling, the ri room temperature or when heated. A suitable implementation is the reaction at a temperature ranging from room temperature to 100°C, during the time from 30 minutes to 60 hours, and preferably from 1 to 30 hours.

Compound (7) receive, by subjecting the compound (20) hydrolysis-decarboxylation. Hydrolysis-decarboxylation of compound (20) can be made by the method shown in reference example 48 below, in a manner analogous to this, the method shown in reaction scheme 4 above, or in a manner analogous to this.

The reaction scheme 12

where R1defined in the formula (1) and X2and A1ddefined above.

The compound (10) receive, by subjecting the compound (21) of the oxidation reaction. This reaction can be carried out by the method shown in reference example 64 below, or in a manner analogous to this, and it is carried out in the presence of known solvent which does not adversely influence the reaction. Such solvents include, for example, water, methanol, ethanol, isopropanol, n-butanol, triptorelin, ethylene glycol and other alcohol solvents; acetone, methyl ethyl ketone, and other ketone solvents; tetrahydrofuran, dioxane, diethyl ether, diglyme, and other ether solvents; methyl acetate, ethyl acetate and other ester solvents; acetonitrile, N,N-dimethylformamide, dimethylsulfoxide and the other is their aprotic polar solvents; methylene chloride, telengard and other halogenated hydrocarbon solvents; organic solvents; mixtures thereof; etc

The reaction is usually carried out using an oxidant(s), such as dimethyl sulfoxide, hexamethylenetetramine, triethylamine-N-oxide, etc.

If necessary, the reaction can be performed in the presence of a suitable base(s). You can use a variety of known inorganic and organic bases. Inorganic bases include, for example, alkali metals (e.g. sodium, potassium, etc.), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), carbonates of alkali metals (such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate etc), lower alkoxides of alkali metals (e.g. sodium methoxide, ethoxide sodium etc), hydrides of alkali metals (for example, sodium hydride, potassium hydride, etc. and the like, Organic bases include, for example, trialkylamine (for example, trimethylamine, triethylamine, N-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-what azabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. When such grounds are liquid, they can also be used as solvents. Such grounds can be used separately or in combination.

The amount of oxidizing agent is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (21).

The amount of base(s) is usually from 0.5 to 10 mol and preferably from 0.5 to 6 mol, per mol of compound (21).

When carrying out the above reaction in the reaction system can be added alkali metals such as potassium iodide, sodium iodide, etc. as reaction accelerators, if necessary.

The reaction temperature is not limited, and usually the reaction can be performed under cooling, at room temperature or when heated. A suitable implementation is the reaction at a temperature ranging from room temperature to 120°C for a time from 30 minutes to 30 hours.

The compounds used as starting substances in the above schemes reactions, can be a suitable salt, and the target compounds obtained by carrying out the above reactions can be in the form of suitable salts.

Each of the target compounds obtained in accordance with the above schemes reactions can be isolated from the reaction mixture is purified for example, by cooling the reaction mixture, separation of the crude reaction product from the reaction mixture using the extraction procedure, such as filtration, concentration, extraction and/or other extraction procedure, followed by purification of the crude product of the reaction column chromatography, recrystallization and/or using other traditional cleaning procedures.

Suitable salts of the compounds (1) are pharmaceutically acceptable salts, including, for example, metal salts, such as alkali metal salts (e.g. sodium salt, potassium salt, etc.), salts of alkaline earth metals (e.g. calcium salt, magnesium salt etc) and so on, ammonium salts, carbonates of alkali metals (e.g. lithium carbonate, potassium carbonate, sodium carbonate, cesium carbonate etc), carbonates of alkali metals (such as lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), hydroxides of alkali metals (for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, etc.), and other salts of inorganic bases; three(lower)alkylamines followed (for example, trimethylamine, triethylamine, N-ethyldiethanolamine etc), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-(lower)alkylphosphine (for example, N-methylmorpholin etc.), DBN, DBU, DABCO the other salts of organic bases; hydrochloride, hydrobromide, hydroiodide, sulfates, nitrates, phosphates and other salts of inorganic acids; the formate, the acetate, propionate, oxalates, malonate, succinate, fumarate, maleates, lactates, malaty, tartratami, citrates, carbonates, picrate, methansulfonate, econsultancy, para-toluensulfonate, glutamate and other organic acid salts; etc

The initial compounds and target compounds represented by formulas in the schemes of reactions above, cover the solvate (e.g. hydrate, ethanolate etc). Preferred solvate includes hydrates.

Compounds represented by formula (1) according to the present invention, of course, include isomers such as geometric isomers, stereoisomers, optical isomers, etc.

Efficiency and the use of the drug

Compounds represented by formula (1), their optically active isomers and their salts (hereinafter designated as compounds of the present invention”) have a specific inhibitory activity against PDE4 and, therefore, are useful as active ingredients for the PDE4 inhibitor.

In addition, due to their PDE4-specific inhibitory action, the compounds of the present invention may be useful as active ingredients of pharmaceutical compositions, used as prophylact the economic and therapeutic agents against various diseases. More specifically, diseases, prevention, and treatment of which can be effectively done by PED4-specific inhibitory effect include various backgrounds acute and chronic (in particular inflammatory and allergen-induced) airway disease (e.g. asthma, chronic obstructive pulmonary disease, etc.); medicine (in particular, hyperplastic, inflammatory and allergic diseases (such as psoriasis (normal), toxic and allergic contact eczema, atopic dermatitis, alopecia areata and other hyperplastic, inflammatory and allergic dermatitis); diseases with functional nervous disorders, such as disorders ability to memorize, memory, and cognition associated with Alzheimer's disease and Parkinson's disease; diseases associated with mental disorders (such as manic-depressive psychosis, schizophrenia, anxiety, etc.); systemic and local arthritis (such as osteoarthritis of the knee, rheumatoid arthritis etc); gastro-intestinal diffuse inflammation (e.g. Crohn's disease and ulcerative colitis); allergic and/or chronic immune-mediated inflammatory diseases of the upper respiratory tract (pharynx, nose) and the adjacent areas (the osovaya sinuses, eyes) (for example, allergic rhinitis/sinusitis, chronic rhinitis/sinusitis, allergic conjunctivitis), etc. Of the above compounds are particularly effective for the prevention and treatment of atopic dermatitis, which makes this disease a suitable target for prevention and treatment.

When used as a PDE4 inhibitor or as a preventive or therapeutic agent from the above various diseases compounds of the present invention can be used as an oral means, solutions for injections, external preparations, etc.

For oral means, for example, the compound can be obtained in such form, as powders, tablets, granules, capsules, syrups, film coated tablets, liquid, etc. Such oral tools may contain pharmaceutically acceptable materials basis and the media and, in addition, may optionally contain a binder, disintegrator, lubricant, moisturizing agents, buffers, preservatives, perfumes and the like, if necessary.

For solution for injection of the compound can be obtained in the form of a solution dissolved in saline, solutions of grape sugar and the like, or in the form of aqueous suspensions.

For external preparations of the compounds, for example, can be obtained in such form, as liquid pharmaceutical PR is parathas, oil medicines, lotions, liniments, emulsions, suspensions, creams, ointments, etc. Such external agents can, optionally, contain a variety of media, materials, bases and additives commonly used in external preparations, and examples include water, oils, surfactants, solubilization components, emulsifiers, colorants (dyes and pigments, fragrances, preservatives, disinfecting agents, thickeners, antioxidants, hepatoblastoma substances, substances for pH control, deodorizing substances, etc.

When used as a PDE4 inhibitor or as a preventive or therapeutic agent from the above various diseases effective dose and number of doses per day of the compounds vary depending on the purpose of use, the type of connection, age, body weight, symptoms, etc. of the subject, and may not be appointed in the same way. For example, an inhibitor or a tool can be introduced in a dose of from 0.1 to 1000 mg of the compounds(compounds) of the present invention per day per adult, and this dose can be administered one or more doses per day.

In addition, other points of view, the present invention provides a method of treatment or prophylaxis of the above various diseases including stage introduction the effective dose of the compounds(compounds) of the present invention to a mammal, such as people.

Moreover, since the compounds of the present invention have inhibitory activity against the production of TNF-α, they are useful as active ingredients for the funds to suppress the production of TNF-α. Diseases in which useful such action on the inhibition of production of TNF-α include disease prevention and treatment which can effectively be accomplished through the PED4-specific inhibitory effect. Dosage form, route of administration and dose means that suppress the production of TNF-α, containing compounds of the present invention, are the same as indicated above for the PDE4 inhibitor and preventive and therapeutic agents.

The effect of the present invention

Compounds of the present invention have a specific inhibitory activity against PDE4 and, thus, are useful as active ingredients for PDE4 inhibitors.

Due to their inhibitory activity, specific against PDE4, the compounds of the present invention are also useful as prophylactic and therapeutic agents against various diseases, including atopic dermatitis.

The best way of carrying out the invention

The present invention is described in more detail below with reference to examples; however, the present image is the buy is not limited to them.

Reference example 1

25 g isovanillin acid suspended in 250 ml of methanol was added 1.5 g of monohydrate para-toluensulfonate acid. The mixture was heated and boiled under reflux during the night. After completion of the reaction the methanol drove away under reduced pressure. The residue was neutralized with saturated aqueous sodium bicarbonate solution and then was extracted with ethyl acetate. After washing with saturated saline solution twice, the organic layer was separated and concentrated under reduced pressure. The residue was purified using column chromatography on silica gel (n-hexane:ethyl acetate = 1:1) to give 24.5 g of methyl 3-hydroxy-4-methoxybenzoate in the form of a white crystalline substance.

1H-NMR (CDCl3) δ: 7,63-7,58 (2H, m), to 6.67 (1H, d, J=8.1 Hz), 5,63 (1H, s), 3,98 (3H, s), 3,90 (3H, s).

Reference example 2

20 g of methyl 3-hydroxy-4-methoxybenzoate obtained in reference example 1 was dissolved in 200 ml of methanol and added to 24.6 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene and 21 g of benzylbromide. The mixture was heated and boiled under reflux during the night. Then the reaction mixture was concentrated, was added to the residue water and was carried out by extraction with ethyl acetate. The extract is washed twice with saturated brine and the organic layer was separated and dried over magnesium sulfate. Then insoluble substances were removed the ri using the filter, the filtrate was concentrated under reduced pressure to get to 25.5 g of methyl 3-benzyloxy-4-methoxybenzoate in the form of a white crystalline substance.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=8,4, 1.8 Hz), to 7.61 (1H, d, J=1,8 Hz), of 7.48-7,28 (5H, m)6,91 (1H, d, J=8,4 Hz)to 5.17 (2H, s), 3,93 (3H, s), a 3.87 (3H, s).

Reference example 3

25 g of methyl 3-benzyloxy-4-methoxybenzoate obtained in reference example 2 was dissolved in 100 ml of acetonitrile and the solution was added 11 g of sodium hydroxide in 100 ml of water. The mixture was stirred under heating at 40°C for 5 hours. The reaction mixture was cooled with ice was added concentrated hydrochloric acid, bringing the pH to approximately 3. Precipitated crystals were collected through filtration and dried under reduced pressure to obtain 22.1 g of 3-benzyloxy-4-methoxybenzoic acid as a white crystalline substance.

1H-NMR (CDCl3) δ: to 7.77 (1H, DD, J=8,4, 1.8 Hz), the 7.65 (1H, d, J=1,8 Hz), of 7.48-7.29 trend (5H, m)6,94 (1H, d, J=8,4 Hz), 5,19 (2H, s), of 3.95 (3H, s).

Reference example 4

20 g of 3-benzyloxy-4-methoxybenzoic acid obtained in reference example 3, suspended in 200 ml of dichloromethane and was added one drop of dimethylformamide. Was added dropwise to 8.1 ml oxalicacid while cooling with ice and stirring. After 2 hours the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 50 ml of tetrahydrofuran and polucheniya was added dropwise to 28%of the resultant aqueous solution of ammonia under ice cooling and stirring. The resulting mixture was stirred for 1 hour and the precipitated crystals were collected through filtration and dried under reduced pressure to obtain 19.9 g of white powdery 3-benzyloxy-4-methoxybenzamide.

1H-NMR (CDCl3) δ: a 7.85-7,28 (7H, m), 6.90 to (1H, d, J=8.1 Hz), 5,67 (2H, users), is 5.18 (2H, s), 3,93 (3H, s)

Reference example 5

15 g of 3-benzyloxy-4-methoxybenzamide obtained in reference example 4, suspended in 450 ml of isopropanol and added to 13.9 g of 1,3-dichloro-2-propanone. The mixture was heated and boiled under reflux during the night. Then the reaction mixture was concentrated to half of its original volume under reduced pressure, the concentrate was added 200 ml of n-hexane and the mixture was stirred. Precipitated crystals were collected through filtration and dried under reduced pressure to obtain 12.2 g of white powdery 2-(3-benzyloxy-4-methoxyphenyl)-4-chlorothioxanthone.

1H-NMR (CDCl3) δ: 7,73-7,71 (3H, m), 7,50-7,29 (5H, m), to 6.95 (1H, d, J=5.7 Hz), 5,20 (2H, s), 4,56 (2H, s), 3,93 (3H, s).

Reference example 6

11 g of 2-(3-benzyloxy-4-methoxyphenyl)-4-chlorothioxanthone obtained in reference example 5, suspended in 220 ml of ethanol and was added 7.5 g of sodium iodide and 9.3 g of phthalimide potassium. The mixture was heated and boiled under reflux during the night. The reaction mixture was cooled with ice and the precipitated crystals were collected at SIP the soup filter. The crude crystals suspended and washed with 100 ml of water. The obtained crystals were dried under reduced pressure to obtain 9.4 g of white powdery 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione.

1H-NMR (CDCl3) δ: to $ 7.91-a 7.85 (2H, m), 7,76-of 7.69 (2H, m), to 7.61-7,58 (3H, m), 7,46 (2H, d, J=6.6 Hz), 7,39-7,26 (3H, m)6,91 (1H, d, J=9 Hz), is 5.18 (2H, s), is 4.85 (2H, s), 3,90 (3H, s).

Reference example 7

9 g of 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione obtained in reference example 6, suspended in 200 ml of ethanol and was added 3.1 ml of hydrazinoacetate. The mixture was heated and boiled under reflux for 3 hours. After cooling, the reaction mixture was added 200 ml of dichloromethane and the mixture was stirred. Insoluble substances were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified using column chromatography on silica gel (NH silica, a product of Fuji company Sylisia Chemical Ltd., dichloromethane:methanol = 20:1) to obtain 4.5 g of pale yellow powder [2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine.

1H-NMR (CDCl3) δ: 7,63-to 7.59 (2H, m), 7,53-7,46 (3H, m), 7,41-7,27 (3H, m) 6,94 (1H, d, J=9 Hz), 5,20 (2H, s)to 3.89 (3H, s), a 3.87 (2H, s), and 2.14 (2H, users).

Reference example 8

15 g of methyl 3-hydroxy-4-methoxybenzoate obtained in reference example 1 was dissolved in 150 ml of di is malformed and added 34 g of potassium carbonate and 22.2 g (methyl bromide)cyclopropane. The mixture was heated at 90°C during the night. To the reaction mixture were added ice water and the precipitated crystals were collected by filtration and washed with plenty of water. The obtained crystals were dried under reduced pressure at room temperature to obtain 18.3 g of white crystalline methyl 3-cyclopropylmethoxy-4-methoxybenzoate.

1H-NMR (CDCl3) δ: to 7.67 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=2.1 Hz), 6.89 in (1H, d, J=8,4 Hz), 3,94-3,86 (8H, m), USD 1.43-of 1.29 (1H, m), 0.70 to EUR 0.58 (2H, m), 0,45-0,30 (2H, m).

Reference example 9

Using 18 g of methyl 3-cyclopropylmethoxy-4-methoxybenzoate obtained in reference example 8, and following the procedure of reference example 3, was received 16.6 g of white crystalline 3-cyclopropylmethoxy-4-methoxybenzoic acid.

1H-NMR (CDCl3) δ: 7,76 (1H, DD, J=8,4, 1.8 Hz), 7,58 (1H, d, J=2.1 Hz), 6,92 (1H, d, J=8,4 Hz), 3,98-to 3.92 (8H, m), USD 1.43-of 1.29 (1H, m), 0.70 to EUR 0.58 (2H, m), and 0.46 and 0.35 (2H, m).

Reference example 10

Using 16.5 g of 3-cyclopropylmethoxy-4-methoxybenzoic acid obtained in reference example 9, and following the procedure described in reference example 4 was obtained 16.2 g of pale yellow powder of 3-cyclopropylmethoxy-4-methoxybenzamide.

1H-NMR (CDCl3) δ: the 7.43 (1H, d, J=2.1 Hz), 7,31 (1H, DD, J=8,4, and 2.1 Hz), to 6.88 (1H, d, J=8.1 Hz), of 5.75 (2H, users), 3,97-to 3.89 (5H, m), 1,40 of 1.28 (1H, m), 0,69-of 0.62 (2H, m), 0,39 is 0.33 (2H, m).

Reference example 11

Using 13 g of 3-cyclopropylmethoxy-4-methoxy who ansamed, obtained in reference example 10, and following the procedure described in reference example 5 was obtained 10.5 g of pale yellow powder 4-chloromethyl-2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazole.

1H-NMR (CDCl3) δ: the 7.65 (1H, d, J=0.9 Hz), 7,20 (1H, DD, J=8,7, and 2.1 Hz), 7,53 (1H, d, J=2.1 Hz), 6,93 (1H, d, J=8,4 Hz), of 4.57 (2H, s), 3,97-3,90 (5H, m), USD 1.43-1,32 (1H, m), 0,71 to 0.63 (2H, m), 0,41-0,35 (2H, m).

Reference example 12

Using 8 g of 4-chloromethyl-2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazole obtained in reference example 11, and following the procedure described in reference example 6 was obtained 10 g of white crystalline 2-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione.

1H-NMR (CDCl3) δ: of 7.90-to 7.84 (2H, m), 7,76-of 7.69 (2H, m), a 7.62 (1H, s), EUR 7.57 (1H, DD, J=8,4, and 2.1 Hz), of 7.48 (1H, d, J=2.1 Hz), 6.89 in (1H, d, J=8,4 Hz), is 4.85 (2H, s), 3.95 to 3,90 (5H, m), 1.41 to 1,31 (1H, m), 0,69-of 0.62 (2H, m), 0,41-0,35 (2H, m).

Reference example 13

Using 9.5 g of 2-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione obtained in reference example 12, and following the procedure described in reference example 7, was received of 5.1 g of a white powder [2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]methylamine.

1H-NMR (CDCl3) δ: to 7.61-of 7.55 (1H, m), 7,53 is 7.50 (2H, m), 6,92 (1H, d, J=8,4 Hz), 3.96 points-a 3.87 (5H, m), 3,83 (2H, s), of 1.41 and 1.33 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Reference example 14

5 g of methyl 3-hydroxy-4-methoxybenzoate obtained in Ref is cnom example 1 was dissolved in 100 ml of dimethylformamide was added 11.3 g of potassium carbonate and 5,64 g isobutyramide. The mixture was heated at 80°C for 6 hours. To the reaction mixture were added ice water and the precipitated crystals were collected by filtration and washed with plenty of water. The obtained crystals were dried under reduced pressure at room temperature with the receipt of 5.85 g of white powder of methyl 3-isobutoxy-4-methoxybenzoate.

1H-NMR (CDCl3) δ: the 7.65 (1H, DD, J=8,4, and 2.1 Hz), 7,53 (1H, d, J=1,8 Hz), to 6.88 (1H, d, J=8.1 Hz), of 3.96 (3H, s), 3,91 (3H, s), 3,82 (2H, d, J=6.9 Hz), 2,20-2,11 (1H, m)of 1.05 (6H, d, J=6,6 Hz).

Reference example 15

Using of 5.85 g of methyl 3-isobutoxy-4-methoxybenzoate obtained in reference example 14, and following the procedure described in reference example 3 was obtained 5.6 g of white powdery 3-isobutoxy-4-methoxybenzoic acid.

1H-NMR (CDCl3) δ: of 7.75 (1H, DD, J=8,4, 1.8 Hz), 7,58 (1H, d, J=2.1 Hz), 6,91 (1H, d, J=8.7 Hz), of 3.94 (3H, s), 3,83 (2H, d, J=6.6 Hz), 2.26 and-a 2.12 (1H, m)of 1.05 (6H, d, J=6,6 Hz).

Reference example 16

Using 5.5 g 3-isobutoxy-4-methoxybenzoic acid obtained in reference example 15, and following the procedure described in reference example 4, was received of 5.1 g of pale yellow powder of 3-isobutoxy-4-methoxybenzamide.

1H-NMR (CDCl3) δ: the 7.43 (1H, d, J=2.1 Hz), 7,31 (1H, DD, J=8,4, and 2.1 Hz), 6.87 in (1H, d, J=8.7 Hz), 5,78 (2H, users), 3,91 (3H, s), 3,83 (2H, d, J=6.6 Hz), 2,25-2,11 (1H, m), 104 (6H, d, J=6,6 Hz).

Reference example 17

Using 5 g of 3-isobutoxy-4-methoxybenzamide obtained in reference example 16, and following the procedure described in reference example 5 was obtained 3.4 g of pale yellow powder 4-chloromethyl-2-(3-isobutoxy-4-methoxyphenyl)oxazole.

1H-NMR (CDCl3) δ: the 7.65 (1H, s), 7,60 (1H, DD, J=8,4, and 2.1 Hz), 7,53 (1H, d, J=2.1 Hz), 6,92 (1H, d, J=8,4 Hz), of 4.57 (2H, s), 3,91 (3H, s), 3,85 (2H, d, J=6.9 Hz), 2,27 and 2.13 (1H, m)of 1.05 (6H, d, J=6,6 Hz).

Reference example 18

Using 3,3 g of 4-chloromethyl-2-(3-isobutoxy-4-methoxyphenyl)oxazole obtained in reference example 17, and following the procedure described in reference example 6 was obtained 4.4 g of white powdery 2-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione.

1H-NMR (CDCl3) δ: to $ 7.91-to 7.84 (2H, m), 7,76-7,71 (2H, m), a 7.62 (1H, s), 7,55 (1H, DD, J=8,4, and 2.1 Hz), 7,49 (1H, d, J=2.1 Hz), to 6.88 (1H, d, J=8,4 Hz), is 4.85 (2H, s)to 3.89 (3H, s), 3,83 (2H, d, J=6.6 Hz), 2,23 and 2.13 (1H, m), of 1.05 (6H, d, J=6,6 Hz).

Reference example 19

Using 4.4 g of 2-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione obtained in reference example 18, and following the procedure described in reference example 7, received 2 g of a white solid [2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]methylamine.

1H-NMR (CDCl3) δ: 7,60-7,51 (3H, m), 6,92 (1H, d, J=8,4 Hz), 3,91 (3H, s), a 3.87-a-3.84 (4H, m), 2,27 and 2.13 (1H, m), 1,71 (2H, users), of 1.06 (6H, d, J=6,6 Hz).

Reference example 20

Using 10 g of methyl 3-hydrox the-4-methoxybenzoate, obtained in reference example 1 and following the procedure described in reference example 14 was obtained 12.5 g of white powder of methyl 4-methoxy-3-(2,2,2-triptoreline)benzoate.

1H-NMR (CDCl3) δ: 7,79 (1H, DD, J=8,7, 1.8 Hz), 7,63 (1H, s)6,94 (1H, d, J=8.7 Hz), 4,42 (2H, q, J=8.1 Hz), of 3.94 (3H, s), 3,91 (3H, s).

Reference example 21

Using 12 g of methyl 4-methoxy-3-(2,2,2-triptoreline)benzoate obtained in reference example 20 following the procedure described in reference example 3, was received with 11.5 g of white powdery 4-methoxy-3-(2,2,2-triptoreline)benzoic acid.

1H-NMR (CDCl3) δ: 7,86 (1H, DD, J=8,4, 1.8 Hz), to 7.67 (1H, d, J=1,8 Hz), 6,97 (1H, d, J=8,4 Hz), 4,43 (2H, q, J=8,4 Hz), of 3.96 (3H, s).

Reference example 22

Using 11.5g 4-methoxy-3-(2,2,2-triptoreline)benzoic acid obtained in reference example 21, and following the procedure described in reference example 4 was obtained 10.8 g of white powdery 4-methoxy-3-(2,2,2-triptoreline)benzamide.

1H-NMR (CDCl3) δ: 7,50 (1H, users), 7,49 (1H, DD, J=8,4, 2.4 Hz), 6,94 (1H, d, J=8,4 Hz), 4,43 (2H, q, J=8,4 Hz), 3,93 (3H, s).

Reference example 23

Using the 10.5 g of 4-methoxy-3-(2,2,2-triptoreline)benzamide obtained in reference example 22, and following the procedure described in reference example 5, was received and 7.1 g of pale yellow powder 4-chloromethyl-2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazole.

1H-NMR (CDCl3) δ: of 7.75 (1H, DD, J=8,4, 21 Hz), 7,66 (1H, users), to 7.64 (1H, d, J=2.1 Hz), 6,98 (1H, d, J=8,4 Hz), 4,56 (2H, s), of 4.45 (2H, q, J=8,4 Hz), of 3.94 (3H, s).

Reference example 24

Using 3 g of 4-chloromethyl-2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazole obtained in reference example 23, and following the procedure described in reference example 6 was obtained 3.6 g of white powdery 2-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl] oxazol-4-ylmethyl}isoindole-1,3-dione.

1H-NMR (CDCl3) δ: to $ 7.91-a 7.85 (2H, m), 7,76-to 7.64 (3H, m), 7,60 (1H, s), to 7.59 (1H, d, J=2.1 Hz), 6,94 (1H, d, J=8.7 Hz), is 4.85 (2H, s), 4,43 (2H, q, J=8,4 Hz), 3,91 (3H, s).

Reference example 25

Using 3.6 g of 2-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}isoindole-1,3-dione obtained in reference example 24, and following the procedure described in reference example 7, was received of 1.93 g of white powdery {2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}methylamine.

1H-NMR (CDCl3) δ: 7,73 (1H, DD, J=8,4, and 2.1 Hz), 7,63 (1H, d, J=2.1 Hz), 7,52 (1H, s), 6,98 (1H, d, J=8,4 Hz), to 4.46 (2H, q, J=8,4 Hz), 3,93 (3H, s), 3,83 (2H, s)of 1.55 (2H, users).

Reference example 26

Using 9.5 g of ethylaniline, and following the procedure described in reference example 14 was obtained 11 g of white powdery ethyl 3-methoxy-4-(2,2,2-triptoreline)benzoate.

1H-NMR (CDCl3) δ: the 7.65 (1H, DD, J=8,4, and 2.1 Hz), 7,60 (1H, d, J=2.1 Hz), of 6.96 (1H, d, J=8,4 Hz), 4,49-to 4.33 (4H, m), 3,93 (3H, s)of 1.39 (3H, t, J=6.9 Hz).

Reference example 27

12 g of ethyl 3-methoxy-4-(2,2,2-triptoreline)benzoe is a, obtained in reference example 26, suspended in 120 ml of 47% Hydrobromic acid and the suspension was heated and boiled under reflux during the night. The reaction mixture was poured into ice water and the precipitated crystals were collected through filtration, washed with plenty of water and then dried under reduced pressure to get a 8.4 g of a pale-red crystalline 3-hydroxy-4-(2,2,2-triptoreline)benzoic acid.

1H-NMR (CDCl3) δ: 7,71-7,66 (2H, m)6,91 (1H, d, J=5,1 Hz), of 5.55 (1H, users), 4,50 (2H, q, J=7,8 Hz).

Reference example 28

of 8.4 g of 3-hydroxy-4-(2,2,2-triptoreline)benzoic acid obtained in reference example 27, suspended in 150 ml of ethanol was added 0.5 ml of concentrated sulfuric acid. The mixture was heated and boiled under reflux during the night. After completion of the reaction the ethanol drove away under reduced pressure. The residue was neutralized with saturated aqueous sodium bicarbonate solution and then was extracted with ethyl acetate. After twice washing with saturated salt solution and the organic layer was separated and concentrated under reduced pressure. The residue was purified using column chromatography on silica gel (n-hexane:ethyl acetate = 1:1) to give 7.2 g of white crystalline ethyl 3-hydroxy-4-(2,2,2-triptoreline)benzoate.

1H-NMR (CDCl3) δ: 7,66-of 7.60 (2H, m, 6,87 (1H, d, J=8.1 Hz), 5,54 (1H, s), 4,48 (2H, q, J=7.8 Hz), 4,35 (2H, q, J=7.2 Hz), to 1.38 (3H, t, J=7.2 Hz).

Reference example 29

Using 7 g of ethyl 3-hydroxy-4-(2,2,2-triptoreline)benzoate obtained in reference example 28, and following the procedure described in reference example 14 was obtained 8.5 g of white powdery ethyl 3-cyclopropylmethoxy-4-(2,2,2-triptoreline)benzoate.

1H-NMR (CDCl3) δ: 7,63 (1H, DD, J=8,7, and 2.1 Hz), 7,58 (1H, d, J=2.1 Hz), 7,00 (1H, d, J=8.7 Hz), 4,48 (2H, q, J=8.1 Hz), 4,35 (2H, q, J=6.9 Hz), 3,92 (2H, d, J=7.2 Hz), 1.41 to 1,25 (4H, m), 0,69 is 0.60 (2H, m), 0,40-0,32 (2H,, m).

Reference example 30

Using 8.5 g of ethyl 3-cyclopropylmethoxy-4-(2,2,2-triptoreline)benzoate obtained in reference example 29, and following the procedure described in reference example 3 was obtained 7.5 g of white powdery 3-cyclopropylmethoxy-4-(2,2,2-triptoreline)benzoic acid.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=8,4, 1.8 Hz), 7,63 (1H, d, J=2.1 Hz), 7,02 (1H, d, J=8.1 Hz), 4,51 (2H, q, J=8.1 Hz), 3,93 (2H, d, J=7,2 Hz), 1,37-1,25 (1H, m), 0,69 is 0.60 (2H, m), 0,41-0,35 (2H, m).

Reference example 31

Using 7 g of 3-cyclopropylmethoxy-4-(2,2,2-triptoreline)benzoic acid obtained in reference example 30, and following the procedure described in reference example 4, was received of 7.35 g of a white solid of 3-cyclopropylmethoxy-4-(2,2,2-triptoreline)benzamide.

1H-NMR (CDCl3) δ: of 7.48 (1H, d, J=2.1 Hz), 7,28-of 7.25 (1H, m), 7,01 (1H, d, J=8,4 Hz), 4,48 (2H, q, J=8,4 Hz), 3,93 (2H, d, J=6.9 Hz), 1,37-1,25 (1H, m), 0,69 is 0.60 (2H, m), 41-0,35 (2H, m).

Reference example 32

Using 5 g of 3-cyclopropylmethoxy-4-(2,2,2-triptoreline)benzamide obtained in reference example 31, and following the procedure described in reference example 5 was obtained 3.1 g of white powder of 4-chloromethyl-2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazole.

1H-NMR (CDCl3) δ: to 7.67 (1H, s), to 7.59-7,56 (2H, m), 7,05 (1H, d, J=9.0 Hz), 4,56 (2H, s), 4,48 (2H, q, J=8,4 Hz), 1,35-of 1.26 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Reference example 33

Using of 0.85 g of 4-chloromethyl-2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazole obtained in reference example 32, and following the procedure described in reference example 6 was obtained 0.6 g of white powdery 2-{2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}isoindole-1,3-dione.

1H-NMR (CDCl3) δ: to $ 7.91-to 7.84 (2H, m), 7,76-of 7.69 (2H, m), of 7.64 (1H, s), 7,60-7,51 (2H, m), 7,01 (1H, d, J=8.7 Hz), is 4.85 (2H, s), to 4.46 (2H, q, J=8,4 Hz), 3,93 (2H, d, J=6.9 Hz), 1,35-1,24 (1H, m), 0,68-0,61 (2H, m), 0,40-0,34 (2H, m).

Reference example 34

Using 0.55 g of 2-{2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}isoindole-1,3-dione obtained in reference example 33, and following the procedure described in reference example 7 was obtained 0.32 g of a white powdery {2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-yl}methylamine.

1H-NMR (CDCl3) δ: to 7.61-7,52 (3H, m), 7,05 (1H, d, J=8.7 Hz), 4,48 (2H, q, J=8,4 Hz), 3,95 (2H, d, J=7,2 Hz) of 3.84 (2H, C), and 1.56 (2H, users), 1,35-1,24 (1H, m), 0.70 to 0,61 (2H, m), 0,41-0,35 (2H, m).

Reference example 35

Using 20 g of 3,4-diethoxybenzoic, and following the procedure described in reference example 5 was obtained 24.5 g of white powder of 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole.

1H-NMR (CDCl3) δ: the 7.65 (1H, s), 7,58 (1H, DD, J=8,4, 1.8 Hz), 7,54 (1H, d, J=1,8 Hz), 6,92 (1H, d, J=8,4 Hz), 4,56 (2H, s), 4,18 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), to 1.48 (6H, t, J=6.9 Hz).

Reference example 36

Using 8 g of 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole obtained in reference example 35, and following the procedure described in reference example 6 was obtained 10 g of white powdery 2-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione.

1H-NMR (CDCl3) δ: 7,88 (2H, m), 7,72 (2H, m), a 7.62 (1H, s), 7,54 (1H, d, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=2.1 Hz), to 6.88 (1H, d, J=8,4 Hz), is 4.85 (2H, s)to 4.16 (2H, q, J=6.9 Hz), 4,11 (2H, q, J=6.9 Hz), 1,47 (6H, t, J=6,9 Hz).

Reference example 37

Using 10 g of 2-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]isoindoline-1,3-dione obtained in reference example 36, and following the procedure described in reference example 7 was obtained 5.7 g of a white powder [2-(3,4-dioxyphenyl)oxazol-4-yl]methylamine.

1H-NMR (CDCl3) δ: 7,56 (1H, d, J=8,4, 1.8 Hz), 7,54 (1H, d, J=1,8 Hz), 7,51 (1H, s)6,91 (1H, d, J=8,4 Hz), 4,18 (2H, q, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), 1,80 (1H, users), a-3.84 (2H, s)to 1.48 (3H, t, J=6.9 Hz), 1,48 (3H, t, J=6.9 Hz).

Reference example 38

Using 2.0 g of 3,4-dimethoxybenzamide, and after the UYa procedure, described in reference example 5 was obtained 2.4 g of white powder of 4-chloromethyl-2-(3,4-acid)oxazole.

1H-NMR (CDCl3) δ: 7,66 (1H, s), a 7.62 (1H, DD, J=8,4, 1.8 Hz), 7,55 (1H, d, J=1,8 Hz), 6,93 (1H, d, J=8,4 Hz)to 4.52 (2H, s), of 3.95 (3H, s), 3,91 (3H, s).

Reference example 39

Using 2.4 g of 4-chloromethyl-2-(3,4-acid)oxazole obtained in reference example 38, and following the procedure described in reference example 6 was obtained 2.3 g of white powdery 2-[2-(3,4-acid)oxazol-4-ylmethyl]isoindoline-1,3-dione.

Reference example 40

Using 2.3 g of 2-[2-(3,4-acid)oxazol-4-ylmethyl]isoindoline-1,3-dione obtained in reference example 39, and following the procedure described in reference example 7 was obtained 1.3 g of a white powder [2-(3,4-acid)oxazol-4-yl]methylamine.

1H-NMR (CDCl3) δ: 7,60 (1H, d, J=8,1, 2,1 Hz), 7,54 (1H, d, J=2.1 Hz), 6,92 (1H, d, J=8.1 Hz), of 3.96 (3H, s), 3,93 (3H, s), 3,85 (2H, s), is 1.81 (2H, users).

Reference example 41

9 g of 4-deformedarse-3-hydroxybenzaldehyde was dissolved in 180 ml of acetonitrile and added to 13.1 g of potassium carbonate and 8.6 ml of benzylbromide. The mixture was stirred at room temperature for 4 hours. Then, insoluble matter was removed through filtration, the filtrate was concentrated and the residue was purified using column chromatography on silica gel (n-hexane:ethyl acetate = 1:1) to give 11.9 g of colorless mA is sanitago 3-benzyloxy-4-deformationally.

1H-NMR (CDCl3) δ: of 10.21 (1H, s), 7,56 (1H, t, J=74,1 Hz), 7,53-7,28 (7H, m), of 6.68 (1H, d, J=8,4 Hz), 5,20 (2H, s).

Reference example 42

6 g of 3-benzyloxy-4-deformationally obtained in reference example 41 was dissolved in 500 ml of acetone was added 17 g of potassium permanganate. The mixture was heated and boiled under reflux during the night. After distillation of the acetone from the reaction mixture, to the residue was added 100 ml of 5N. solution of sodium hydroxide and insoluble substances were removed by means of filtration. To the filtrate was added concentrated hydrochloric acid, bringing the pH to about 3, and the precipitated crystals were collected by means of filtration. The obtained crystals were dried under reduced pressure to obtain 2.1 g of a brownish powdery 3-benzyloxy-4-diplomatchisinau acid.

1H-NMR (CDCl3) δ: 7,78-7,72 (2H, m), 7,73-to 7.32 (5H, m), 7,33-7,24 (1H, m), to 6.67 (1H, t, J=74,1 Hz), 5,20 (2H, s).

Reference example 43

2 g of 3-benzyloxy-4-diplomatchisinau acid obtained in reference example 42, suspended in 40 ml of dichloromethane and was added one drop of dimethylformamide. Dropwise while cooling with ice and stirring was added 0.7 ml of oxalicacid. After 2 hours the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 5 ml of acetone and the resulting solution was added dropwise to 28%of the resultant aqueous solution is of Miaka while cooling with ice and stirring. The resulting mixture was stirred for 1 hour and the precipitated crystals were collected through filtration and dried under reduced pressure to obtain 1.9 g of white powdery 3-benzyloxy-4-deformationand.

1H-NMR (CDCl3) δ: a 7.62 (1H, d, J=1,8 Hz), 7,45-7,20 (7H, m), 6,63 (1H, t, J=74,4 Hz), 5,19 (2H, s), to 4.73 (2H, users).

Reference example 44

1.8 g of 3-benzyloxy-4-deformationand obtained in reference example 43, suspended in 50 ml of isopropanol and added 1,17 g of 1,3-dichloro-2-propanone. The mixture was heated and boiled under reflux during the night. The reaction mixture was concentrated and the resulting residue was purified using column chromatography on silica gel (dichloromethane). The crude crystals are recrystallized from isopropanol to obtain 0.7 g of white powdery 2-(3-benzyloxy-4-deformational)-4-chlorothioxanthone.

1H-NMR (CDCl3) δ: 7,44 (1H, d, J=1,8 Hz), of 7.70 (1H, s)of 7.48-to 7.32 (5H, m), 7,28-7,24 (1H, m), 6,63 (1H, t, J=74,7 Hz), to 5.21 (2H, s), of 4.57 (2H, s).

Reference example 45

of 0.37 g of 2-(3-benzyloxy-4-deformational)-4-chlorothioxanthone obtained in reference example 44 was dissolved in 20 ml of ethanol and added to 0.23 g of sodium iodide and 0.27 g of phthalimide potassium. The mixture was heated and boiled under reflux for 4 hours. Then the reaction mixture was concentrated, to the residue was added water and sushestvovali extraction with ethyl acetate. The organic layer was twice washed with water and concentrated to remove solvent and the residue was purified using column chromatography on silica gel (dichloromethane:methanol = 20:1) to obtain 0.3 g of white powdery 2-[2-(3-benzyloxy-4-deformational)oxazol-4-ylmethyl]isoindoline-1,3-dione.

1H-NMR (CDCl3) δ: of 7.90-to 7.84 (2H, m), 7,76-7,71 (4H, m), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), 7,47-7,30 (5H, m), 7,22 (1H, d, J=2.4 Hz), 6,60 (1H, t, J=74,7 Hz), 5,20 (2H, s), to 4.87 (2H, s).

Reference example 46

0.3 g of 2-[2-(3-benzyloxy-4-deformational)oxazol-4-ylmethyl]isoindoline-1,3-dione obtained in reference example 45, suspended in 10 ml of ethanol was added 0.1 ml of hydrazinoacetate. The mixture was heated and boiled under reflux for 2 hours. After cooling the reaction mixture, the precipitated insoluble substance was removed by means of filtration. The filtrate was concentrated under reduced pressure obtaining of 0.13 g of colorless oily [2-(3-benzyloxy-4-deformational)oxazol-4-yl]methylamine.

1H-NMR (CDCl3) δ: 7,74 (1H, d, J=1,8 Hz), to 7.61 (1H, DD, J=7,8, 1.8 Hz), 7,47 (1H, d, J=1,8 Hz), 7,45-7,31 (5H, m), 7,26-7,20 (1H, m), 6,62 (1H, t, J=74,7 Hz), to 5.21 (2H, s), 3,85 (2H, users).

Reference example 47

the 5.25 g of sodium hydride suspended in 150 ml of tetrahydrofuran was added dropwise under ice cooling a solution of 14.4 g of diethylmalonate in 75 ml of tetrahydrofuran for 15 minutes. After the remesiana for 30 minutes was added dropwise a solution of 25 g of 2-(3-benzyloxy-4-methoxyphenyl)-4-chlorothioxanthone, obtained in reference example 5 in 150 ml of dimethylformamide for 15 minutes. After adding dropwise, the mixture was stirred at a temperature of from 50 to 60°C for 4 hours and cooled with ice was added aqueous saturated solution of ammonium chloride. After stirring the mixture for 30 minutes was added water and was carried out by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent drove by distillation. The residue was recrystallized from a mixture of ethyl acetate and diisopropyl ether to obtain 26.5 g of white powdery dimethyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]malonate.

1H-NMR (DMSO-d6) δ: 7,89 (1H, s), to 7.59-7,31 (7H, m), to 7.15 (1H, d, J=7.8 Hz), 5,16 (2H, s), 3,90-a-3.84 (4H, m), 3,71 (6H, s), 3.04 from (2H, d, J=7,8 Hz).

Reference example 48

26,52 g of dimethyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]malonate obtained in reference example 47, suspended in 53 ml of dimethyl sulfoxide was added 2,62 g of lithium chloride and 1.12 ml of distilled water. The mixture was stirred at 130°C for 4 hours. Then the reaction mixture was left to cool, added water and was carried out by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent drove by distillation. The residue was purified using column chromatography on silica gel (n-hexane:ethyl acetate 3:1) to obtain 16 g of a white powder of methyl 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]propionate.

1H-NMR (CDCl3) δ: 7,62-to 7.59 (2H, m), 7,47 (2H, d, J=6.9 Hz), 7,40-7,31 (4H, m), 6,93 (1H, d, J=8,4 Hz), 5,20 (2H, s)to 3.92 (3H, s), of 3.69 (3H, s), only 2.91 (2H, t, J=7.2 Hz), of 2.72 (2H, t, J=7.2 Hz).

Reference example 49

of 0.48 g of sodium hydride suspended in 15 ml of tetrahydrofuran and within 15 minutes was added dropwise a solution of 1.31 g of diethylmalonate in 7.5 ml of tetrahydrofuran. Then the mixture was stirred for 30 minutes, within 15 minutes the solution was added 3.0 g of 4-chloromethyl-2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazole obtained in reference example 32, dissolved in 15 ml of dimethylformamide. After adding dropwise, the mixture was heated at a temperature of from 50 to 60°C with stirring for 4 hours. To the reaction mixture under ice cooling was added a saturated aqueous solution of ammonium chloride and stirring was continued for 30 minutes. Was added water and was carried out by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent drove by distillation. To the residue was added to 8.0 ml of dimethyl sulfoxide, 0.35 g of lithium chloride and 0.15 ml of distilled water and the mixture was heated with stirring at 130°C for 4 hours. Then the reaction mixture was left to cool, added water and was carried out by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent drove by distillation. The remainder of the imali using column chromatography on silica gel (n-hexane:ethyl acetate = 4:1) to give 1.63 g of colorless, oily methyl 3-{2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propionate.

1H-NMR (CDCl3) δ: 7,56-7,53 (2H, m), the 7.43 (1H, s),? 7.04 baby mortality (1H, d, J=8,4 Hz), 4,47 (2H, q, J=8,4 Hz), of 3.94 (2H, d, J=6.6 Hz), of 3.69 (3H, s), only 2.91 (2H, t, J=7.2 Hz), of 2.72 (2H, t, J=7.2 Hz), 0,88 (1H, t, J=6.6 Hz), 0,69-of 0.65 (2H, m), and 0.40 and 0.35 (2H, m).

Reference example 50

0.5 g of 2-cyclopropylethanol and 3.1 ml of triethylamine were dissolved in 10 ml of ethyl acetate and cooling with ice and stirring was added 0.75 ml of methanesulfonanilide. After stirring for 30 minutes to the reaction mixture was added water and was carried out by extraction. The organic layer was washed twice with water and concentrated by removing the solvent under reduced pressure to obtain 1 g of pale yellow oily 2-cyclopropylacetylene.

1H-NMR (CDCl3) δ: the 4.29 (2H, t, J=6.6 Hz), 3,03 (3H, s)of 1.66 (2H, q, J=6.6 Hz), 0,84-0,70 (1H, m), 0,54 of 0.47 (2H, m), 0,20-0,10 (2H, m).

Reference example 51

Using 2 g of 2-cyclopentylamine and following the procedure described in reference example 50 was obtained 3.4 g of pale yellow oily 2-cyclopentylpropionate.

1H-NMR (CDCl3) δ: 4,24 (2H, t, J=6.6 Hz), 3,03 (3H, s), 1,95-of 1.73 (5H, m), 1.70 to to 1.48 (4H, m), 1,29 was 1.06 (2H, m).

Reference example 52

Using 0.5 g of cyclopentylamine and following the procedure described in reference example 50 was obtained 0.7 g of pale yellow oily cyclopentadienylmanganese.

1H-NMR (CDCl3) δ: 4,11 (2H, d, J=6.9 Hz), 3.04 from (3H, s), 2,38-of 2.23 (1H, m), 1,86 to 1.76 (2H, m), 1,74-of 1.53 (4H, m), 1,36-1,2 (2H, m).

Reference example 53

25 g of 1-(2-hydroxyphenyl)ethanone and 76 g of potassium carbonate suspended in 500 ml of acetonitrile was added 31 ml of allylbromide. The mixture was stirred at room temperature for 48 hours. The reaction mixture was filtered to remove nerastvorim substances and the filtrate was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 4:1) to give 34 g of a pale yellow oily 1-(2-allyloxyphenyl)ethanone.

1H-NMR (CDCl3) δ: 7,73 (1H, DD, J=7,8, 1.8 Hz), 7,46-7,40 (1H, m), 7,02-6,93 (2H, m), 6,15-of 6.02 (1H, m), 5,47-and 5.30 (2H, m), 4,66-br4.61 (2H, m)of 2.64 (3H, s).

Reference example 54

40 g of 3,4-diethoxybenzoic and 80 g of methyl 5-bromo-4-oxopentanoate (containing about 35% of methyl 3-bromo-4-oxopentanoate) was added to 400 ml of dimethylformamide and the mixture was stirred at 130°C for 16 hours. The reaction mixture was concentrated under reduced pressure and diluted with ethyl acetate. Was slowly added ethyl acetate (500 ml) and saturated sodium bicarbonate solution (500 ml) with stirring and continued stirring. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified column chromatography on silica gel (ethyl acetate:n-hexane = 1:8 to 1:4) to obtain 18 g of a white powder of methyl 3-[2-(3,4-diethoxy enyl)oxazol-4-yl]propionate.

1H-NMR (CDCl3) δ: 7,65-of 7.55 (2H, m), 7,51 (1H, s), 6,93 (1H, d, J=8.1 Hz), 4,19 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), 3,80 (3H, s), 3.00 and-2,90 (2H, m), 2,70-2,60 (2H, m)of 1.50 (3H, t, J=6.9 Hz), for 1.49 (3H, t, J=6,9 Hz).

Reference example 55

of 37.9 g of 3,4-dibenzylethylenediamine and 28.8 g of 1,3-dichloro-2-propanone suspended in 500 ml of propanol and the suspension was heated and boiled under reflux for 3 days. After cooling, the reaction mixture was concentrated to half of its original volume under reduced pressure and added to 300 ml of diisopropyl ether. Precipitated crystals were collected by filtration and recrystallized from a mixture of acetone-methanol-diisopropyl ether. The obtained crystals were dried under reduced pressure to get to 20.1 g of a colorless powder of 2-(3,4-bis(benzyloxy)phenyl)-4-chlorothioxanthone.

1H-NMR (CDCl3) δ: 7,66 (1H, d, J=2.1 Hz), to 7.64 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), 7,50-7,28 (10H, m), of 6.99 (1H, d, J=8,4 Hz), with 5.22 (2H, s), a total of 5.21 (2H, s)4,55 (2H, s).

Reference example 56

Using 10 g of 2-(3,4-bis(benzyloxy)phenyl)-4-chlorothioxanthone obtained in reference example 55, and following the procedure described in reference example 47 was obtained 12.3 g of colorless oily dimethyl 2-[2-(3,4-bis(benzyloxy)phenyl)oxazol-4-ylmethyl]malonate.

1H-NMR (CDCl3) δ: to 7.61 (1H, d, J=2.1 Hz), 7,58-7,27 (12H, m), 6,97 (1H, d, J=8,4 Hz), 5,23-5,20 (4H, m)to 3.89 (1H, t, J=7.5 Hz), of 3.75 (3H, s), of 3.73 (3H, s)3,18 (2H, d, J=7.5 Hz).

Ref CNY example 57

Using 12.3 g of dimethyl 2-[2-(3,4-bis(benzyloxy)phenyl)oxazol-4-ylmethyl]malonate obtained in reference example 56, and following the procedure described in reference example 48 was obtained 4 g of a pale red powder of methyl 3-[2-(3,4-bis(benzyloxy)phenyl)oxazol-4-yl]propionate.

1H-NMR (CDCl3) δ: 7,63 (1H, d, J=2.1 Hz), EUR 7.57-7,27 (12H, m), 6,97 (1H, d, J=8,4 Hz), to 5.21 (2H, d, J=7,2 Hz), of 3.69 (3H, s), 2,90 (2H, t, J=7.2 Hz), 2,72 (2H, d, J=7,2 Hz).

Reference example 58

Using of 29.4 g of 3-ethoxy-4-methoxybenzamide and 57 g of 1,3-dichloro-2-propanone and following the procedure described in reference example 55, was given to 19.9 g of white powder of 4-chloromethyl-2-(3-ethoxy-4-methoxyphenyl)oxazole.

1H-NMR (CDCl3) δ: the 7.65 (1H, s), to 7.61 (1H, DD, J=8,1, 2,1 Hz), 7,55 (1H, d, J=2.1 Hz), 6,92 (1H, d, J=8.1 Hz), 4,56 (2H, s), 4,18 (2H, q, J=6.9 Hz), 3,93 (3H, s)of 1.50 (3H, t, J=6.9 Hz).

Reference example 59

25 g of ethyl 3,4-dihydroxybenzoate was dissolved in 250 ml of dimethylformamide was added 5.5 g of sodium hydride under ice cooling and stirring. The mixture was stirred and was added dropwise a solution of 16.3 ml benzylbromide in 10 ml of dimethylformamide. After adding dropwise, the mixture was stirred at room temperature overnight. To the reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer twice washed with water and concentrated by removing the solvent under reduced pressure. Polucen the th residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1) to give 15 g of the crude crystals. The crude crystals are recrystallized from a mixture of 30 ml of n-hexane and 15 ml of ethyl acetate to obtain 8.6 g of colorless plate-crystalline ethyl 4-benzyloxy-3-hydroxybenzoate.

1H-NMR (CDCl3) δ: to 7.67-7,47 (2H, m), 7,41-7,30 (5H, m)6,94 (1H, d, J=8.7 Hz), 5,67 (1H, s), 5,16 (2H, s), 4,34 (2H, q, J=7.2 Hz), of 1.37 (3H, t, J=7.2 Hz).

Reference example 60

Using ethyl 4-benzyloxy-3-hydroxybenzoate obtained in reference example 59, and following the procedure described in reference example 2, was obtained ethyl 4-benzyloxy-3-ethoxybenzoate.

1H-NMR (CDCl3) δ: to 7.61-of 7.55 (2H, m), 7,45-7,27 (5H, m), 6.90 to (1H, d, J=8.1 Hz), to 5.21 (2H, s), 4,34 (2H, q, J=6.9 Hz), 4,17 (2H, q, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz), of 1.37 (3H, t, J=6.9 Hz).

Reference example 61

Using ethyl 4-benzyloxy-3-ethoxybenzoate obtained in reference example 60, and following the procedure described in reference example 3 was obtained 4-benzyloxy-3-ethoxybenzoyl acid.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=8,4, 1.2 Hz), to 7.61 (1H, d, J=1.2 Hz), 7,45-7,28 (5H, m), 6,92 (1H, d, J=8,4 Hz), 5,23 (2H, s)to 4.17 (2H, q, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz).

Reference example 62

Using 4-benzyloxy-3-ethoxybenzoyl acid obtained in reference example 61, and following the procedure described in reference example 4 was obtained 4-benzyloxy-3-ethoxybenzene in the form of colorless needle-like crystals.

1H-NMR (CDCl3) δ: 7,47-7,21 (7H, m), to 6.88 (1H, d, J=8.1 Hz), to 5.21 (2H, s), 4,18 (2H, q, J=7.2 Hz), to 1.48 (3H, t, J=2 Hz).

Reference example 63

Using 4-benzyloxy-3-ethoxybenzene obtained in reference example 62, and following the procedure described in reference example 5 was obtained a colorless powder 4-chloromethyl-2-(4-benzyloxy-3-ethoxyphenyl)oxazol.

1H-NMR (CDCl3) δ: to 7.64 (1H, s), EUR 7.57-7,30 (7H, m)6,94 (1H, d, J=8,4 Hz), 5,20 (2H, s), 4,56 (2H, s), 4,20 (2H, q, J=7.2 Hz), for 1.49 (3H, t, J=7.2 Hz).

Reference example 64

for 6.81 g of sodium iodide and 5,09 g of sodium bicarbonate was added to a suspension of 10 g of 2-(3-benzyloxy-4-methoxyphenyl)-4-chlorothioxanthone obtained in reference example 5 in 60 ml of dimethylsulfoxide. The mixture was heated at 120°C under stirring for 30 minutes. Then the reaction mixture was allowed to cool, added a saturated saline solution and was carried out by extraction with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain the 2,98 g yellow oily 2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-carbaldehyde.

1H-NMR (CDCl3) δ: 9,98 (1H, s), compared to 8.26 (1H, s), 7,71 (1H, DD, J=8,1, 2,1 Hz), 7,69 (1H, users), of 7.48 (2H, userd, J=8,4 Hz), 7,42-7,31 (3H, m), 6,98 (1H, d, J=8.1 Hz), to 5.21 (2H, s), of 3.95 (3H, s).

Reference example 65

Using 4-chloromethyl-2-[4-methoxy-3-(2,2,2-triptoreline)FeNi is]oxazol, obtained in reference example 23, and following the procedure described in reference example 64, received a colorless powder 2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-carbaldehyde.

1H-NMR (CDCl3) δ: 9,99 (1H, s), of 8.28 (1H, s), 7,82 (1H, DD, J=8,4, and 2.1 Hz), 7,71 (1H, d, J=2.1 Hz), 7,01 (1H, d, J=8,4 Hz), to 4.46 (2H, q, J=8,4 Hz), of 3.95 (3H, s).

Reference example 66

Using 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole obtained in reference example 35, and following the procedure described in reference example 64, received a pale yellow powder of 2-(3,4-dioxyphenyl)oxazol-4-carbaldehyde.

1H-NMR (CDCl3) δ: 9,99 (1H, s), compared to 8.26 (1H, s), the 7.65 (1H, DD, J=8,4, and 2.1 Hz), a 7.62 (1H, d, J=2.1 Hz), 6,94 (1H, d, J=8,4 Hz), 4,19 (2H, q, J=7.2 Hz), 4,17 (2H, q, J=7.2 Hz), 1,50 (6H, t, J=7.2 Hz).

Reference example 67

Using 12.7 g of 3-isopropoxy-4-methoxybenzoic acid and following the procedure described in reference example 4 was obtained a white powdery 3-isopropoxy-4-methoxybenzamide.

1H-NMR (CDCl3) δ: 7,46 (1H, d, J=2.1 Hz), 7,34 (1H, DD, J=8,4, and 2.1 Hz), 6.87 in (1H, d, J=8,4 Hz), to 5.93 (1H, users), to 4.62 (1H, m), 3,90 (3H, s)to 1.38 (6H, d, J=6.0 Hz).

Reference example 68

Using 11.4 g of 3-isopropoxy-4-methoxybenzamide obtained in reference example 67, and 25 g of 1,3-dichloro-2-propanone and following the procedure described in reference example 5 was obtained 12.2 g of white powder of 4-chloromethyl-2-(3-isopropoxy-4-methoxyphenyl)oxazole.

1H-NMR CDCl 3) δ: the 7.65 (1H, s), to 7.61 (1H, DD, J=8,4, and 2.1 Hz), EUR 7.57 (1H, d, J=2.1 Hz), 6,93 (1H, d, J=8,4 Hz), with 4.64 (1H, m), a 4.53 (2H, s), 3,90 (3H, s)of 1.40 (6H, d, J=6.0 Hz).

Reference example 69

Using 4-chloromethyl-2-(3-isopropoxy-4-methoxyphenyl)oxazole obtained in reference example 68, and following the procedure described in reference example 64, received a pale yellow powder of 2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-carbaldehyde.

1H-NMR (CDCl3) δ: 9,99 (1H, s), of 8.27 (1H, s), to 7.68 (1H, DD, J=8,1, 2,1 Hz), to 7.64 (1H, d, J=2.1 Hz), to 6.95 (1H, d, J=8.1 Hz), of 4.67 (1H, Sept., J=6.3 Hz), to 3.92 (3H, s)of 1.41 (6H, d, J=6.3 Hz).

Reference example 70

10 g of 1-(2-hydroxyphenyl)ethanone was dissolved in 100 ml of dimethylformamide was added 11.2 ml chloromethylmethylether ether and 25.4 g of potassium carbonate. The mixture was stirred at 50°C for 6 hours and then at room temperature for 4 days. Then insoluble substances were removed by means of filtration from the reaction mixture, was added to the filtrate ice water and was carried out by extraction with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure and the residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 5:1) obtaining of 6.26 g of colorless oily 1-(2-methoxyethoxymethyl)ethanone.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), the 7.43 (1H, TD, J=7,8, 1.8 Hz), 7,18 (1H, d, J=7.8 Hz), 7,05 (1H, t, J7,8 Hz), 5,28 (2H, s), 3,52 (3H, s)of 2.64 (3H, s).

Reference example 71

3 g of methyl 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]propionate obtained in reference example 54, suspended in 5 ml of methanol was added 5 ml of 20%aqueous sodium hydroxide solution. The mixture was heated and boiled under reflux for 4 hours. After cooling the reaction mixture to room temperature was carried out by extraction with dichloromethane. The dichloromethane layer was washed with water and dried over anhydrous magnesium sulfate. Carried out the distillation of the solvent and the obtained crystals were dried to obtain 2.8 g of white powdery 3-[2-(3,4-acid)oxazol-4-yl]propionic acid.

1H-NMR (CDCl3) δ: 7,65-of 7.55 (3H, m), 7,51 (1H, d, J=2.1 Hz), 6,91 (1H, d, J=8,4 Hz)to 4.17 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), 3.00 and-2,90 (2H, m), 2,90 is 2.80 (2H, m)to 1.48 (3H, t, J=6.9 Hz), to 1.48 (3H, t, J=6,9 Hz).

Reference example 72

Using 10 g of 4-benzyloxy-3-methoxybenzamide and following the procedure described in reference example 54, received 2 g of white powder of methyl 3-[2-(4-benzyloxy-3-methoxyphenyl)oxazol-4-yl]propionate.

1H-NMR (CDCl3) δ: 7,54-7,28 (8H, m) 6,93 (1H, d, J=8.1 Hz), 5,20 (2H, s), of 3.97 (3H, s), 3,68 (3H, s), only 2.91 (2H, t, J=7.5 Hz), of 2.64 (2H, t, J=7.5 Hz).

Reference example 73

Using 2 g of methyl 3-[2-(4-benzyloxy-3-methoxyphenyl)oxazol-4-yl]propionate obtained in reference example 72, and following the procedure described in the reference p is the iMER 71, received of 1.03 g of white powdery 3-[2-(4-benzyloxy-3-methoxyphenyl)oxazol-4-yl]propionic acid.

1H-NMR (CDCl3) δ: 12,20 (1H, s), 7,86 (1H, s), 7,51-7,31 (7H, m) 7,17 (1H, d, J=8,4 Hz), further 5.15 (2H, s), 3,85 (3H, s)of 2.75 (2H, t, J=7.5 Hz), at 2.59 (2H, t, J=7.5 Hz).

Reference example 74

0.4 g of 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole obtained in reference example 35 was dissolved in 15 ml of methylamine (40%solution in methanol)was heated and boiled under reflux for 1 hour. The reaction mixture was concentrated and the resulting residue was dried under reduced pressure to get 0,23 g yellow oily [2-(3,4-acid)oxazol-4-ylmethyl]methylamine.

1H-NMR (CDCl3) δ: 8,00 (1H, s), 7,58 is 7.50 (2H, m), 6.90 to (1H, d, J=8,4 Hz), 4,21-4,10 (6H, m), was 2.76 (3H, s)and 1.51-of 1.45 (6H, m).

Reference example 75

Using ethyl 2-chloroacetoacetate and 16 g of 3,4-diethoxybenzoic and following the procedure described in reference example 5 was obtained 3.8 g of ethyl [2-(3,4-acid)oxazol-4-yl]acetate.

1H-NMR (CDCl3) δ: to 7.64 (1H, s), 7,60 is 7.50 (2H, m)6,91 (1H, d, J=8.1 Hz), 4,25-4,10 (6H, m)to 3.58 (2H, s), 1,50-of 1.40 (6H, m)of 1.29 (3H, t, J=6.9 Hz).

Reference example 76

0.35 g of sociallyengaged was added to 30 ml of tetrahydrofuran with ice cooling and stirring and slowly added ethyl [2-(3,4-acid)oxazol-4-yl]acetate obtained in reference example 75, with stirring. After stirring at room temp is the temperature for 3 hours, the mixture was stirred under ice cooling for 3 hours and was added 0.35 ml of water, 0,35 ml of 15%aqueous sodium hydroxide solution and 1.05 ml of water, in that order. The reaction mixture was dried over anhydrous magnesium sulfate, and the insoluble matter was then removed by means of filtration. The filtrate was concentrated under reduced pressure to obtain 2.5 g of a colorless crystalline 2-[2-(3,4-acid)oxazol-4-yl]ethanol.

1H-NMR (CDCl3) δ: 7,56 (1H, d, J=8,4, and 2.1 Hz), 7,52 (1H, d, J=2.1 Hz), 7,46 (1H, s)6,91 (1H, d, J=8,4 Hz)to 4.17 (2H, q, J=7.2 Hz), is 4.15 (2H, q, J=7.2 Hz), of 3.94 (2H, q, J=5.4 Hz), to 2.94 (1H, t, J=5.4 Hz), of 2.81 (2H, t, J=5.4 Hz), to 1.48 (3H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Reference example 77

2.0 g of 2-[2-(3,4-acid)oxazol-4-yl]ethanol obtained in reference example 76, and 2.3 g of triphenylphosphine was added to 20 ml of dichloromethane and slowly added 2.9 g of tetrabromide carbon under ice cooling and stirring. After the temperature of the mixture reached room temperature, stirring was continued for 1.5 hours. The reaction mixture was concentrated and the residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 8:1) to obtain 1.9 g of a colorless crystalline 4-(2-bromacil)-2-(3,4-dioxyphenyl)oxazole.

1H-NMR (CDCl3) δ: 7,60 is 7.50 (3H, m)6,91 (1H, d, J=8,4 Hz), 4,18 (2H, q, J=7.2 Hz), 4,14 (2H, q, J=7.2 Hz), to 3.67 (2H, t, J=6.9 Hz), 3,14 (2H, t, J=6.9 Hz), to 1.48 (3H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Reference example 78

Using 1.5 g of 4-(2-bromacil)-2-(3,4-di is toxigenic)oxazole, obtained in reference example 77, and following the procedures of reference examples 6 and 7 was obtained 0.8 g of yellow oily 2-[2-(3,4-dioxyphenyl)oxazol-4-yl]ethylamine.

1H-NMR (CDCl3) δ: 7,60 is 7.50 (3H, m)6,91 (1H, d, J=8,4 Hz)to 4.17 (2H, q, J=7.2 Hz), is 4.15 (2H, q, J=7.2 Hz), 3,90-of 3.80 (2H, m), 3.00 and-2,90 (2H, m), of 1.85 (2H, users), to 1.48 (3H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Reference example 79

Using 10.4 g of 3,4-diethoxybenzoic and 19.5 g of ethyl 3-bromo-2-oxopropionate and following the procedure described in reference example 5 was obtained by 12.9 g of white powdery ethyl 2-(3,4-dioxyphenyl)oxazol-4-carboxylate.

1H-NMR (CDCl3) δ: 8,21 (1H, d, J=0.9 Hz), to 7.64 (1H, DD, J=8,1, 0.9 Hz), 7,63 (1H, s), 6,92 (1H, d, J=8.1 Hz), 4,42 (2H, q, J=7.2 Hz), 4,17 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz), of 1.41 (3H, t, J=7.2 Hz).

Reference example 80

Using 10 g of ethyl 2-(3,4-dioxyphenyl)oxazol-4-carboxylate obtained in reference example 79 and following the procedure described in reference example 71, was obtained 8.6 g of white powdery 2-(3,4-dioxyphenyl)oxazol-4-carboxylic acid.

1H-NMR (CDCl3) δ: 8,24 (1H, s), 7,60 is 7.50 (3H, m), of 6.02 (1H, users), of 4.13 (4H, q, J=6.9 Hz), of 1.46 (3H, t, J=6.9 Hz), of 1.39 (3H, t, J=6.9 Hz).

Reference example 81

Using 0.4 g of ethyl [2-(3,4-dioxyphenyl)oxazol-4-yl]acetate obtained in reference example 75 and following the procedure described in reference example 71, was obtained 0.35 g of a white powder [2-(3,4-dioxyphenyl)OK the azole-4-yl]acetic acid.

1H-NMR (CDCl3) δ: 7,65-of 7.55 (3H, m), 7,51 (1H, d, J=2.1 Hz), 6,91 (1H, d, J=8,4 Hz)to 4.17 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), to 3.73 (2H, s), for 1.49 (6H, t, J=6.9 Hz).

Reference example 82

Using 3 g of 4-chloromethyl-2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazole obtained in reference example 23, and following the procedure described in reference example 47, was received at 1.91 g of colorless oily dimethyl 2-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}malonate.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=8,4, and 2.1 Hz), 7,60 (1H, d, J=2.1 Hz), 7,42 (1H, s), of 6.96 (1H, d, J=8,4 Hz), of 4.44 (2H, q, J=6.9 Hz), 3,93 (3H, s)to 3.89 (1H, t, J=7.5 Hz), 3,18 (2H, d, J=7.5 Hz).

Reference example 83

Using 1.9 g of dimethyl 2-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}malonate obtained in reference example 82, and following the procedure described in reference example 48 was obtained 1.44 g of colorless, oily methyl 3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propionate.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=8,4, and 2.1 Hz), 7,60 (1H, d, J=2.1 Hz), 7,42 (1H, s), of 6.96 (1H, d, J=8,4 Hz), of 4.45 (2H, q, J=6.9 Hz), 3,92 (3H, in), 3.75 (3H, s), only 2.91 (2H, t, J=7.5 Hz), of 2.72 (2H, t, J=7.5 Hz).

Example 1

3.5 g of [2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 7, suspended in 70 ml of acetone. To the resulting suspension was added 2.3 g of 1-hydroxybenzotriazole, and 3.3 g of the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 3.8 g of 2-ethoxybenzoyl is islote and the mixture was heated and boiled under reflux for one hour. The reaction mixture was cooled and acetone drove away under reduced pressure. To the residue was added water and then carried out the extraction with ethyl acetate. The organic layer was twice washed with water and concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (dichloromethane:methanol = 20:1) to obtain 4.6 g of white powdery N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene.

1H-NMR (CDCl3) δ: 8,55 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,65-to 7.61 (3H, m), 7,49-7,29 (6H, m), to 7.09 (1H, t, J=7.5 Hz),? 7.04 baby mortality-6,92 (2H, m), 5,20 (2H, s), br4.61 (2H, d, J=5.4 Hz), of 4.16 (2H, q, J=6.9 Hz), 3,93 (3H, s), of 1.26 (3H, t, J=6.9 Hz).

Example 2

the 4.65 g of N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene obtained in example 1 was dissolved in 90 ml of ethanol and was added 0.45 g of 10% palladium-on-carbon in powder form. The mixture was stirred in hydrogen atmosphere at room temperature for one hour. The catalyst was removed via filtration and the filtrate is then concentrated under reduced pressure to obtain 3.7 g of white crystalline N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,62-of 7.55 (3H, m), 7,41 (1H, TD, J=7.5 Hz, 1.8 Hz), 7,06 (1H, t, J=7.2 Hz), 6,95-to 6.88 (2H, m), 5,74 (1H, s), to 4.62 (2H, d, J=5,1 Hz)to 4.17 (2H, q, J=6.9 Hz), of 3.95 (3H, s)of 1.47 (3H, t, J=6.9 Hz).

Example 3

0.2 g of N-[2-(3-HYDR the XI-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene, obtained in example 2 and 0.3 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 4 ml of ethanol and to the mixture was added 0.14 g (methyl bromide)cyclopropane. The mixture was heated and boiled under reflux during the night. The reaction mixture was allowed to cool, then to the mixture was added water and was carried out by extraction with ethyl acetate. The mixture was twice washed with water and then the organic layer was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to give 0.18 g of white powdery N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene.

1H-NMR (CDCl3) δ: 8,55 (1H, users), 8,24 (1H, DD, J=7,8, and 2.1 Hz), 7,62-to 7.59 (2H, m), 7,53 (1H, d, J=2.1 Hz), 7,45-7,39 (1H, m), 7,07 (1H, TD, J=8.1 Hz, 1.2 Hz), 6,95-6,91 (2H, m), to 4.62 (2H, d, J=5.4 Hz), 4,18 (2H, q, J=6,9 Hz), 3,94-to 3.92 (5H, m), for 1.49 (3H, t, J=6.9 Hz), 1,42 is 1.34 (1H, m), 0,71-of 0.64 (2H, m), 0,41-0,35 (2H, m).

Example 4

0.3 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene obtained in example 2, and 0.22 g of potassium carbonate was dissolved in 10 ml of dimethylformamide, and to the mixture was added 0.34 g 1,1,1-Cryptor-2-iodata. The mixture was stirred under heating at 50°C during the night. The reaction mixture was allowed to cool, then to the mixture was added water and was carried out by extraction with ethyl acetate. The mixture was twice washed with water and then the organic layer was concentrated under decreased the pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain 0.14 g of white powdery N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-ethoxybenzene.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,8, and 2.1 Hz), 7,73 (1H, DD, J=8,4, and 2.1 Hz), 7,65-7,63 (2H, m), 7,45-7,39 (1H, m), 7,09-7,01 (1H, m), 6,99-of 6.90 (2H, m), to 4.62 (2H, d, J=5.4 Hz), 4,55 (2H, q, J=8,4 Hz), 4,32 (2H, q, J=6.9 Hz), 3,93 (3H, s), for 1.49 (3H, t, J=6.9 Hz).

Using 0.2 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene obtained in example 2, the compounds of examples 5 to 14 were obtained in the same manner as in example 3.

Example 5

N-[2-(3-butoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Yield 0.2 g

White powder

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,8, and 2.1 Hz), 7,62-rate of 7.54 (3H, m), 7,45-7,39 (1H, m), 7,07 (1H, t, J=8.1 Hz), of 6.96-of 6.90 (2H, m), to 4.62 (2H, d, J=5.4 Hz), 4,18 (2H, q, J=6.9 Hz), 4,10 (2H, t, J=6.9 Hz), 3,92 (3H, s), 1,92-to 1.82 (2H, m), 1,59 to 1.47 (5H, m), and 1.00 (3H, t, J=7.5 Hz).

Example 6

N-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Output 0,22 g

Colorless oily substance

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,24 (1H, DD, J=7,8, and 2.1 Hz), 7,62-rate of 7.54 (3H, m), 7,45-7,39 (1H, m), 7,07 (1H, t, J=8.1 Hz), of 6.96-of 6.90 (2H, m), 4,91-a 4.86 (1H, m), to 4.62 (2H, d, J=5.4 Hz), 4,17 (2H, q, J=6.9 Hz), 3,90 (3H, C)2,02 is 1.60 (8H, m), for 1.49 (3H, t, J=6.9 Hz).

Example 7

N-{2-[3-(3-hydroxypropoxy)-4-methoxyphenyl]oxazol-4-ylmethyl}-2-ethoxybenzene

Yield 0.12 g

White powder

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, d, J=7.8 Hz), 7,62-rate of 7.54 (3H, m), 7,45-7,39 (1H, m), 7,09-7,06 (1H, m), of 6.96-of 6.90 (2H, m), to 4.62 (2H, d, J=5.4 Hz), 4,29-4,16 (4H, m), 3,92-3,79 (5H, m), 2.57 m (1H, users), 2,12 (2H, t, J=5.4 Hz), for 1.49 (3H, t, J=6.9 Hz).

Example 8

N-[2-(4-methoxy-3-(2-propenyloxy)phenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Output 0,19 g

White powder

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,70-7,63 (3H, m), 7,45-7,39 (1H, m), 7,07 (1H, TD, J=8,4, and 0.9 Hz), 6,98-6,93 (2H, m), 4,84 (2H, d, J=2.4 Hz), 4,63 (2H, DD, J=5,4, and 0.9 Hz), 4,19 (2H, q, J=7,2 Hz), of 3.94 (3H, s)to 2.54 (1H, t, J=2.4 Hz), 1,50 (3H, t, J=7.2 Hz).

Example 9

N-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Output 0,22 g

A white powdery substance

1H-NMR (CDCl3) δ: 8,55 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,62-rate of 7.54 (3H, m), 7,44-7,39 (1H, m), 7,07 (1H, t, J=8.1 Hz), of 6.96-6,91 (2H, m), to 4.62 (2H, d, J=5.4 Hz), 4,23-to 4.14 (4H, m), 3,93 (3H, s), 1,53 of 1.46 (6H, m).

Example 10

N-[2-(4-methoxy-3-(2-oxiranylmethyl)phenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Yield 27 mg

White powder

1H-NMR (CDCl3) δ: 8,54 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), to 7.67-7,58 (3H, m), 7,45-7,38 (1H, m), 7,07 (1H, t, J=7.8 Hz), to 6.95 (2H, d, J=8,4 Hz), to 4.62 (2H, d, J=5,1 Hz), 4,36-4,07 (4H, m), 3,93 (3H, s), 3.46 in-to 3.41 (1H, m)of 2.92 (1H, t, J=4.5 Hz), 2,80 was 2.76 (1H, m)to 1.48 (3H, t, J=7.2 Hz).

Example 11

N-[2-(4-methoxy-3-propoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Output 0,19 g

White powder

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J7,8, 1,8 Hz), 7,63-rate of 7.54 (3H, m), 7,45-7,39 (1H, m), 7,07 (1H, TD, J=8,4, 1.2 Hz), of 6.96-6,91 (2H, m), 4,63 (2H, DD, J=5,1, 0.9 Hz), 4,18 (2H, q, J=6.9 Hz), 4,06 (2H, t, J=6.9 Hz), to 3.92 (3H, s), 1,97-of 1.85 (2H, m), 1,49 (3H, t, J=6.9 Hz), with 1.07 (3H, t, J=7.2 Hz).

Example 12

N-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Yield 0.17 g

White powder

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,62-of 7.55 (3H, m), 7,45-7,38 (1H, m), 7,07 (1H, t, J=7.8 Hz), of 6.96-6,91 (2H, m), 4.72 in-4,59 (3H, m), 4,18 (2H, q, J=6.9 Hz), 3,91 (3H, s), for 1.49 (3H, t, J=6,9 Hz), of 1.41 (6H, d, J=6.3 Hz).

Example 13

N-[2-(3-(3-butenyloxy)-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Yield 0.21 g

White powder

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,63-of 7.55 (3H, m), 7,45-7,38 (1H, m), 7,07 (1H, t, J=7.8 Hz), of 6.96-6,91 (2H, m), 5,97-5,88 (1H, m), 5,23-5,10 (2H, m), to 4.62 (2H, DD, J=5,1, 0.9 Hz), 4,21-4,12 (4H, m)to 3.92 (3H, s), 2,68-2,60 (2H, m), for 1.49 (3H, t, J=6.9 Hz).

Example 14

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

Yield 84 mg

White powder

1H-NMR (CDCl3) δ: 8,54 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,62-7,53 (2H, m), 7,44 (1H, d, J=1,8 Hz), 7,41 (2H, TD, J=7,8, 1.8 Hz), 7,06 (1H, t, J=7.8 Hz), 6,95-of 6.90 (2H, m), to 4.62 (2H, d, J=5.4 Hz), 4,18 (2H, q, J=6,9 Hz), 3,91 (3H, s), 3,85 (2H, d, J=6.9 Hz), measuring 2.20 (1H, cut, J=6,9, and 6.6 Hz), for 1.49 (3H, t, J=6.9 Hz), of 1.06 (6H, d, J=6,6 Hz).

Example 15

Using 0.2 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene obtained in example 2 N-{2-[4-methoxy-3-(3,3,3-cryptocracy)phenyl]oxazol-4-ylmethyl}-2-ethoxybenzene who was lucali in the same way, as in example 4.

The output 60 mg

White powder

1H-NMR (CDCl3) δ: 8,55 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7.68 per-7,63 (2H, m), 7,56 (1H, d, J=2.1 Hz), 7,45-7,39 (1H, m), 7,07 (1H, t, J=7.2 Hz), 6,97-6,93 (2H, m), to 4.62 (2H, d, J=5.4 Hz), 4,32 (2H, t, J=6.9 Hz), 4,18 (2H, q, J=6.9 Hz), to 3.92 (3H, s), 2,78-to 2.67 (2H, m), for 1.49 (3H, t, J=6.9 Hz).

Example 16

1.5 g of [2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 7, suspended in 30 ml of acetone. To the resulting suspension was added 1.0 g of 1-hydroxybenzotriazole, 1.4 g of the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.8 g of 3-metilakrilovoe acid and the mixture was heated and boiled under reflux for 30 minutes. The reaction mixture was cooled and acetone drove away under reduced pressure. To the residue was added water and then carried out the extraction with ethyl acetate. The organic layer twice washed with water and the solvent was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (dichloromethane:methanol = 20:1) to obtain 1.5 g of white powdery N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide.

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,39 (1H, d, J=7.5 Hz), 7,65-7,28 (10H, m)6,94 (1H, d, J=9.0 Hz), to 5.21 (2H, s), 4,58 (2H, DD, J=5,7, and 0.9 Hz), 3,93 (3H, s), was 2.76 (3H, s).

Example 17

1.5 g of N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide obtained in the use of the e 16, was dissolved in 50 ml of ethanol and to the mixture was added 0.1 g of 10% palladium-on-carbon in powder form. The mixture was stirred in hydrogen atmosphere at 50°C for two hours. The catalyst was removed via filtration and the filtrate is then concentrated to obtain 1.3 g of white crystalline N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide.

1H-NMR (CDCl3) δ: 8,58 (1H, users), scored 8.38 (1H, DD, J=4,5, and 0.9 Hz), 7,63 (1H, s), a 7.62 rate of 7.54 (3H, m), 7,32-7,27 (1H, m), 6.90 to (1H, d, J=8,4 Hz), of 5.75 (1H, users), 4,58 (2H, DD, J=6,0, 0.9 Hz), of 3.94 (3H, s)of 2.75 (3H, s).

Example 18

0.15 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide obtained in example 17, and 0.5 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 4 ml of ethanol and to the mixture was added to 0.13 g bromocyclopentane. The mixture was heated and boiled under reflux for 3 hours. The reaction mixture was allowed to cool, then to the mixture was added water and was carried out by extraction with ethyl acetate. Extract twice washed with water and the organic layer was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to give 0.11 g of white powdery N-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide.

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,39 (1H, DD, J=4,8, and 0.9 Hz), 7,62-7,53 (4H, m), 7,32-7,27 (1H, m)6,91 (1H, d, J=8,4 Hz), 4,88 (1H, TT,J=3.3 Hz), 4,59 (2H, DD, J=5,7, and 0.9 Hz), with 3.89 (3H, s), was 2.76 (3H, s), 2,07-to 1.79 (6H, m), 1.70 to to 1.60 (2H, m).

Example 19

0.15 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide obtained in example 17, and 0.18 g of potassium carbonate was dissolved in 4 ml of dimethylformamide and to the mixture was added to 0.19 g of 1,1,1-Cryptor-2-iodata. The mixture was stirred under heating at 80°C during the night. The reaction mixture was allowed to cool, then to the mixture was added water and was carried out by extraction with ethyl acetate. Extract twice washed with water and the organic layer was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to give 0.11 g of white powdery N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-3-methylphthalimide.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, DD, J=4,5, 1.2 Hz), 7,73 (1H, DD, J=8,7, and 2.1 Hz), 7,63-EUR 7.57 (3H, m), 7,32-7,27 (1H, m), 6,97 (1H, d, J=8,4 Hz), 4,59 (2H, DD, J=5,7, and 0.9 Hz), to 4.46 (2H, q, J=8,4 Hz), 3,93 (3H, s)that was 2.76 (3H, s).

Example 20

Using 0.2 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide obtained in example 17, 0.11 g of N-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide was obtained in the same manner as in example 3.

Colourless crystals

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,39 (1H, DD, J=4,8, 1.5 Hz), 7,65 is 7.50 (4H, m), 7,30 (1H, DD, J=7,8, and 4.8 Hz), 6,92 (1H, d, J=8.1 Hz), 4,59 (1H, DD, J=6,0, 0.6 Hz), 4,19 (2H, the, J=6,9 Hz)to 4.17 (2H, q, J=6.9 Hz), to 3.92 (3H, s), was 2.76 (3H, s)of 1.50 (3H, t, J=6.9 Hz).

Example 21

Using 0.15 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide obtained in example 17, 45 mg of N-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide was obtained in the same manner as in example 3.

Colourless crystals

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, DD, J=4,5, 1.5 Hz), 7,65 is 7.50 (4H, m), 7,30 (1H, DD, J=7,8, and 4.5 Hz), 6,93 (1H, d, J=8,4 Hz), 6,12 (1H, m), the 5.45 (1H, m), 5,32 (1H, DD, J=9,6, 1.5 Hz), 4,70 (2H, d, J=5.4 Hz), 4,59 (1H, d, J=6.0 Hz), to 3.92 (3H, s), was 2.76 (3H, s).

Example 22

170 mg of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide obtained in example 17, was dissolved in 10 ml of tetrahydrofuran. To the resulting solution was added 134 mg of 2-hydroxyindole, 0.5 ml of diisopropylcarbodiimide (40%solution in toluene) and 202 mg three(n-butyl)phosphine, and the mixture was stirred at room temperature overnight and at 50°C for 2.5 hours. To the reaction mixture were added 100 mg of 2-hydroxyindole, 0.5 ml of diisopropylcarbodiimide (40%solution in toluene) and 200 mg three(n-butyl)phosphine, and the mixture was stirred at 50°C for 5 hours and at room temperature over night. The reaction mixture was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate:methylene chloride = 1:1:1) to obtain 92 mg of N-{2-[3-(indan-2-yl) - Rev. XI)-4-methoxyphenyl]oxazol-4-ylmethyl}-3-methylphthalimide.

Pale-yellow oily substance

1H-NMR (CDCl3) δ: 8,59 (1H, users), 8,39 (1H, d, J=3.3 Hz), 7,65-7,16 (9H, m), 6,93 (1H, d, J=8.1 Hz), and 5.30 (1H, TT, J=6,6, 3,9 Hz), 4,60 (2H, d, J=5.7 Hz), 3,86 (3H, s), of 3.46 (2H, DD, J=16,8, and 6.6 Hz), with 3.27 (2H, DD, J=16,8, 3,9 Hz), was 2.76 (3H, s).

Example 23

Using 0.88 g of [2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 7, of 1.03 g of white powdery N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 7,72-7,46 (9H, m), 7,40-7,27 (3H, m), to 6.95 (1H, d, J=8,4 Hz), 6,34 (1H, users), 5,20 (2H, s), 4,59 (2H, d, J=5.4 Hz), 3,93 (3H, s).

Example 24

Using 1.0 g of N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane obtained in example 23, 0.66 g of white powdery N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane was obtained in the same manner as in example 2.

1H-NMR (CDCl3) δ: 7,71 is 7.50 (7H, m), 6.90 to (1H, d, J=8,4 Hz), to 6.39 (1H, users), USD 5.76 (1H, s), 4,59 (2H, d, J=5.4 Hz), of 3.94 (3H, s).

Example 25

Using 0.2 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane obtained in example 24, 0.18 g of white powdery N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane was obtained in the same manner as in example 3.

1H-NMR (CDCl3) δ: 7,72 is 7.50 (7H, m), 6,93 (1H, d, J=8,4 Hz), 6,34 (1H, s),4,60 (2H, d, J=5.4 Hz), 3,93 (3H, s), 1,42-1,32 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 26

Using 0.2 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane obtained in example 24, 40 mg of white powdery N-{2-[3-(3-hydroxypropoxy)-4-methoxyphenyl]oxazol-4-ylmethyl}-2-cryptomelane was obtained in the same manner as in example 3.

1H-NMR (CDCl3) δ: 7,71 is 7.50 (7H, m), 6,92 (1H, d, J=8,4 Hz), 6,34 (1H, users), 4,60 (2H, d, J=5.4 Hz), 4,28 (2H, q, J=5.7 Hz), 3,98-3,86 (5H, m), 2,47 (1H, t, J=5.7 Hz), 2,15-2,07 (3H, m).

Example 27

Using 0.5 g of 2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 7, and 0.62 g of white powdery N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-ethoxypyridine was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,24 is 8.22 (2H, m), of 7.64-of 7.60 (3H, m), 7,50-7,46 (2H, m), 7,41-7,28 (5H, m)6,94 (1H, d, J=9.0 Hz), 5,20 (2H, s), br4.61 (2H, d, J=5.7 Hz), 4,17 (2H, q, J=6.9 Hz), 3,93 (3H, s)of 1.50 (3H, t, J=6,9 Hz).

Example 28

Using 0.6 g of N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-ethoxypyridine obtained in example 27, 0.5 g of a white amorphous N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-ethoxypyridine was obtained in the same manner as in example 2.

1H-NMR (CDCl3) δ: 8,25 is 8.22 (2H, m), of 7.64 (1H, d, J=1,8 Hz), 7,60-rate of 7.54 (2H, m), 7,39-7,28 (2H, m)6,91 (1H, d, J=8.1 Hz), 5,71 (1H, users), br4.61 (2H, DD, J=5,4, and 0.9 Hz), 4,17 (2H, q, J=6.9 Hz), of 3.94 (3H, s), of 1.52 (3H, t, J=6,9 Hz).

P the emer 29

Using 0.5 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-ethoxypyridine obtained in example 28, 0.18 g of a white amorphous N-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-ethoxypyridine was obtained in the same manner as in example 3.

1H-NMR (CDCl3) δ: 8,25 is 8.22 (2H, m), of 7.64 (1H, s), 7,58 (1H, DD, J=8,4, and 2.1 Hz), 7,53 (1H, d, J=1,8 Hz), 7,39-to 7.32 (2H, m)6,91 (1H, d, J=8,4 Hz), 4,91-a 4.86 (1H, m), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 4,17 (2H, q, J=6,9 Hz), the 3.89 (3H, s), 2.05 is-to 1.79 (6H, m), 1,66-to 1.60 (2H, m)and 1.51 (3H, t, J=6.9 Hz).

Example 30

Using 0.31 g of 2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 7, 0.16 g of white powdery N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-(2,2,2-triptoreline)benzamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: by 8.22 (1H, DD, J=7,8, 1.8 Hz), 7,82 (1H, users), 7,63-of 7.60 (3H, m), 7,49-7,27 (6H, m), 7,19 (1H, t, J=7.2 Hz), of 6.96-to 6.88 (2H, m), 5,19 (2H, s), to 4.62 (2H, d, J=5.4 Hz), 4,47 (2H, q, J=7,8 Hz)to 3.92 (3H, s).

Example 31

Using 0.16 g of N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-(2,2,2-triptoreline)benzamide obtained in example 30, 0.11 g of white powdery N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-(2,2,2-triptoreline)benzamide was obtained in the same manner as in example 2.

1H-NMR (CDCl3) δ: 8,21 (1H, DD, J=7,8, 1.8 Hz), to 7.84 (1H, users), a 7.62 rate of 7.54 (3H, m), 7,49-the 7.43 (1H, m), 7,19 (1H, TD, J=7,8, and 0.9 Hz), 5,71 (1H, s), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 4,48 (2H, q, J=7.8 Hz), of 3.94(3H, C).

Example 32

Using 0.11 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-(2,2,2-triptoreline)benzamide obtained in example 31, 78 mg of a white amorphous N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-(2,2,2-triptoreline)benzamide was obtained in the same manner as in example 3.

1H-NMR (CDCl3) δ: by 8.22 (1H, DD, J=7,8, and 2.1 Hz), 7,83 (1H, users), to 7.61-EUR 7.57 (3H, m), 7,53 (1H, d, J=2.1 Hz), 7,50-the 7.43 (1H, m), 7,19 (1H, TD, J=7,8, and 0.9 Hz), 6,94-to 6.88 (2H, m), 4,63 (2H, DD, J=5,4, and 0.9 Hz), 4,48 (2H, q, J=7,8 Hz), 1,42-1,32 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 33

Using 0.5 g of 2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 7, of 0.68 g of pale yellow powdery N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxybenzamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,39 (1H, users), 8,23 (1H, DD, J=4,8, 1.8 Hz), 7,65-of 7.60 (3H, m), 7,50-7,28 (6H, m), was 7.08 (1H, t, J=7.2 Hz), 6,98-6,93 (2H, m), a total of 5.21 (2H, s), br4.61 (2H, DD, J=5,4, and 0.9 Hz), of 3.95 (3H, s), 3,93 (3H, s).

Example 34

Using of 0.67 g of N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxybenzamide obtained in example 33, 0.52 g of white amorphous N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxybenzamide was obtained in the same manner as in example 2.

1H-NMR (CDCl3) δ: 8,43 (1H, users), 8,23 (1H, DD, J=7,8, and 2.1 Hz), 7,63 (1H, s), 7,60-rate of 7.54 (2H, m), 7,47-7,41 (1H, m), 7,10-7,05 (1H, m), 6,97 (1H, d, J=8,4 Hz)6,91 (1H, d, J=8.1 Hz), 5,74 (1H, users)and 4.2 (2H, DD, J=5,4, and 0.9 Hz), of 3.97 (3H, s), of 3.95 (3H, s).

Example 35

Using 0.5 g of N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxybenzamide obtained in example 34, 0.39 g of white powdery N-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxybenzamide was obtained in the same manner as in example 3.

1H-NMR (CDCl3) δ: to 8.41 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,63 (1H, s), to 7.59 (1H, DD, J=8,4, 1.8 Hz), 7,54 (1H, d, J=1,8 Hz), of 7.48-7,42 (1H, m), was 7.08 (1H, t, J=7.8 Hz), 6,98 (1H, d, J=8.1 Hz), 6,92 (1H, d, J=8,4 Hz), 4,91-to 4.87 (1H, m), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), of 3.97 (3H, s), 3,90 (3H, s), 2.05 is and 1.80 (6H, m), 1,66-to 1.59 (2H, m).

Example 36

0.2 g of [2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 13, suspended in 4 ml of acetone. To the resulting suspension were added 0.2 g of 1-hydroxybenzotriazole, 0.29 grams of the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.14 g of 3-metilakrilovoe acid and the mixture was heated and boiled under reflux for 30 minutes. The reaction mixture was cooled, then to the mixture was added water and was carried out by extraction with ethyl acetate. The organic layer twice washed with water and the solvent was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 1:1) to obtain 0.16 g of white powdery N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylpyran the foreign Ministry.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, DD, J=4,5, 1.2 Hz), 7,63-EUR 7.57 (3H, m), 7,52 (1H, d, J=2.1 Hz), 7,33-7,28 (1H, m), 6,92 (1H, d, J=8,4 Hz), 4,59 (2H, DD, J=6,0, 0.9 Hz), 3,97-3,90 (5H, m), was 2.76 (3H, s), 1.41 to 1,31 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Using 0.2 g of [2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 13, the compounds of examples 37 to 43 was obtained in the same manner as in example 1.

Example 37

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-isopropoxybenzoic

Yield 0.17 g

White powder

1H-NMR (CDCl3) δ: 8,62 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,62-7,58 (2H, m), 7,54 (1H, d, J=2.1 Hz), 7,43-7,38 (1H, m), 7,05 (1H, TD, J=8,1, 0.9 Hz), 6,97-6,91 (2H, m), 4,76-of 4.67 (1H, m), br4.61 (2H, DD, J=5,4, and 0.9 Hz), 3,94-3,90 (5H, m), 1.41 to 1,38 (7H, m), 0,69-of 0.64 (2H, m), 0,41-0,35 (2H, m).

Example 38

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methylbenzamide

Yield 0.16 g

White powder

1H-NMR (CDCl3) δ: to 7.64 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,41-7,16 (3H, m), 6,93 (1H, d, J=8,4 Hz), of 6.31 (1H, users), 4,58 (2H, DD, J=5,4, and 0.9 Hz), 3.95 to to 3.92 (5H, m), the 2.46 (3H, s), 1,42-1,32 (1H, m), 0,70 to 0.63 (2H, m), 0,41-0,35 (2H, m).

Example 39

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-ethylbenzamide

Yield 0.15 g

White powder

1H-NMR (CDCl3) δ: to 7.64 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=1,8 Hz), 7,41-7,16 (3H, m), 6,93 (1H, d, J=8.1 Hz), of 6.31 (1H, users), of 4.57 (2H, d, J=5.4 Hz), 3.95 to to 3.92 (5H, m), of 2.81 (2H, q, J=7.5 Hz), 1,42-1,32 (1H, m)of 1.23 (3H, t, J=7.5 Hz), 0.70 to 0,63(2H, m)of 0.41 and 0.35 (2H, m).

Example 40

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-chlorobenzamide

Yield 0.17 g

White powder

1H-NMR (CDCl3) δ: 7,71-7,66 (2H, m), to 7.59 (1H, DD, J=8,4, 1.8 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,42-7,29 (3H, m), 6,93 (1H, d, J=8,4 Hz), to 6.75 (1H, users), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 3.95 to to 3.92 (5H, m), 1.41 to to 1.32 (1H, m), 0.70 to to 0.63 (2H, m), 0,41-0,35 (2H, m).

Example 41

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-5-fluoro-2-methoxybenzamide

Output 0,19 g

White powder

1H-NMR (CDCl3) δ: to 8.45 (1H, users), 7,94 (1H, DD, J=9,6, and 3.3 Hz), 7,63 (1H, s), to 7.61 (1H, DD, J=8,1, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,17-7,10 (1H, m), 6,95-of 6.90 (2H, m), br4.61 (2H, d, J=5.4 Hz), 3.96 points-to 3.92 (8H, m), 1,40-1,30 (1H, m), 0.70 to of 0.64 (2H, m), 0,41-0,35 (2H, m).

Example 42

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-4-fluoro-2-methoxybenzamide

Output 0,19 g

White powder

1H-NMR (CDCl3) δ: 8,27-8,21 (2H, m), 7,63-7,58 (2H, m), 7,52 (1H, d, J=2.1 Hz), 6,93 (1H, d, J=8,4 Hz), for 6.81-6,74 (1H, m), 6,69 (1H, DD, J=10,2, 2,1 Hz), 4,60 (2H, DD, J=5,4, and 0.9 Hz), 3,97-are 3.90 (8H, m), 1,40-of 1.30 (1H, m), 0,70-of 0.64 (2H, m), 0,41-0,35 (2H, m).

Example 43

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-fluoro-6-methoxybenzamide

Yield 0.17 g

White powder

1H-NMR (CDCl3) δ: the 7.65 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,34-7,27 (1H, m), 6,92 (1H, d, J=8,4 Hz), 6,76-6,70 (2H, m), 6,51 (1H, users), br4.61 (2H, d, J=5.7 Hz), 3,94-3,91 (5H, m), 3,85 (3H, s), 1,42 to 1.31 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 44

Using 0.4 g of [2-(3-cyclopropylmethoxy and-4-methoxyphenyl)oxazol-4-yl]methylamine, obtained in reference example 13, N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methylsulfonylbenzoyl was obtained in the same manner as in example 1.

Yield 0.4 g

White powder

1H-NMR (CDCl3) δ: 7.68 per (1H, s), to 7.61-7,56 (2H, m)to 7.50 (1H, d, J=1,8 Hz), 7,34-7,17 (3H, m), 6,95-of 6.90 (2H, m), br4.61 (2H, DD, J=5,4, and 0.9 Hz), 3.95 to to 3.92 (5H, m), the 2.46 (3H, s), 1,42 to 1.31 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 45

Using 0.7 g of [2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 13, N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-hydroxyproline was obtained in the same manner as in example 1.

Yield 0.6 g

White powder

1H-NMR (CDCl3) δ: 12,02 (1H, s), to 8.45 (1H, users), of 8.06 (1H, DD, J=4.2, and 1.8 Hz), 7,63-to 7.59 (2H, m), 7,52 (1H, s), 7,37-7,29 (3H, m), 6,93 (1H, d, J=8,4 Hz), 4,60 (2H, d, J=6.0 Hz), 3.96 points-3,93 (5H, m), 1.56 to of 1.33 (1H, m), 0.70 to of 0.64 (2H, m), 0,42-0,36 (2H, m).

Using 0.1 g of [2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 13, the compounds of examples 46-56 was obtained in the same manner as in example 1.

Example 46

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxybenzamide

Output 0.1 g

White powder

1H-NMR (CDCl3) δ: 8,40 (1H, users), 8,23 (1H, DD, J=7,8, and 2.1 Hz), of 7.64-7,58 (2H, m), 7,52 (1H, d, J=2.1 Hz), of 7.48-7,42 (1H, m), was 7.08 (1H, dt, J=7,8, and 0.9 Hz), 6,99-6,91 (2H, m), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 3,97-3,91 (8H, m), 1,40-1,32 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 47

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomaterial

Yield 43 mg

White powder

1H-NMR (CDCl3) δ: 8,02 (1H, DD, J=7,8, 1.8 Hz), of 7.64-7,27 (6H, m), 7,10 (1H, users), 6,93 (1H, d, J=8,4 Hz), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 3.95 to to 3.92 (5H, m), 1,43 of 1.28 (1H, m), is 0.69 to 0.63 (2H, m), 0,41-0,36 (2H, m).

Example 48

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-propoxybenzene

Output 0.1 g

White powder

1H-NMR (CDCl3) δ: 8,50 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz) to 7.61-7,58 (2H, m), 7,53 (1H, d, J=1,8 Hz), 7,44-7,38 (1H, m), 7,06 (1H, t, J=7.8 Hz), 6,95-6,91 (2H, m), to 4.62 (2H, d, J=5,1 Hz)4,06 (2H, t, J=6.6 Hz), 3.95 to 3,68 (5H, m)to 1.86 (2H, TD, J=7,5, and 6.6 Hz), 1.41 to 1,31 (1H, m)to 0.96 (3H, t, J=7.5 Hz), 0.70 to 0,61 (2H, m), 0,41-0,35 (2H, m).

Example 49

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]pyrazin-2-carboxamide

Yield 90 mg

White powder

1H-NMR (CDCl3) δ: 9,42 (1H, s), is 8.75 (1H, d, J=2.4 Hz), charged 8.52 (1H, DD, J=2.7, and 1.5 Hz), of 8.25 (1H, users), to 7.64 (1H, s), 7,60 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 6,92 (1H, d, J=8,4 Hz), 4,63 (2H, DD, J=5,4, and 0.9 Hz), 4,11-to 3.92 (5H, m), 1,40-1,32 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 50

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-ethoxypyridine

Yield 85 mg

White powder

1H-NMR (CDCl3) δ: 8,24 is 8.22 (2H, m), of 7.64 (1H, s), 7,60 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=2.1 Hz), 7,39-to 7.32 (2H, m), 6,92 (1H, d, J=8,4 Hz), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 4,17 (2H, q, J=6.9 Hz), 3,98-to 3.92 (5H, m), of 1.52 (3H, t, J=6.9 Hz), 1,43-1,32 (1H, m), 0,71 to 0.63 (2H, m), 0,41-0,35 (2H, m).

Por the measures 51

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-butoxybenzene

Yield 70 mg

White powder

1H-NMR (CDCl3) δ: 8,48 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,63-to 7.59 (2H, m), 7,53 (1H, d, J=2.1 Hz), 7,45-7,38 (1H, m), 7,06 (1H, TD, J=8,4, and 0.9 Hz), of 6.96-6,91 (2H, m), br4.61 (2H, d, J=5,1 Hz), 4.09 to (2H, t, J=6,6 Hz), 3,94-3,91 (5H, m), of 1.84 and 1.75 (2H, m), of 1.46 and 1.33 (3H, m), is 0.84 (3H, t, J=7.2 Hz), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 52

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-isobutoxide

Yield 0.12 g

White powder

1H-NMR (CDCl3) δ: 8,46 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,62-7,58 (2H, m), 7,52 (1H, d, J=1,8 Hz), 7,41 (1H, t, J=7.2 Hz), 7,06 (1H, t, J=7.2 Hz), 6,95-6,91 (2H, m), to 4.62 (2H, d, J=5,1 Hz), 3.95 to to 3.92 (5H, m), 3,86 (2H, d, J=6.3 Hz), 2,20-2,10 (1H, m), 1,40 to 1.31 (1H, m)of 0.95 (6H, d, J=6.6 Hz), 0.70 to 0,63 (2H, m), 0,41 is 0.37 (2H, m).

Example 53

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-isopropoxypyridine

Output 0.1 g

White powder

1H-NMR (CDCl3) δ: 8,28 is 8.25 (2H, m), 7,63 (1H, s), 7,60 (1H, DD, J=8,4, and 2.1 Hz), 7,52 (1H, d, J=2.1 Hz), 7,38-7,31 (2H, m), 6,93 (1H, d, J=8,4 Hz), 4,70-br4.61 (3H, m), 3,98-3,90 (5H, m), 1,42-1,31 (7H, m), 0.70 to 0,61 (2H, m,), 0,41-0,35 (2H, m).

Example 54

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-metilsulfonilmetane

Yield 85 mg

White powder

1H-NMR (CDCl3) δ: 7,70-7,66 (2H, m), to 7.59 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=2.1 Hz), 7,43-to 7.32 (2H, m), 7,27-7,22 (2H, m), 6,92 (1H, d, J=8.7 Hz), br4.61 (2H, DD, J=5,4, 0.6 Hz), 3.95 to to 3.92 (5H, m), 2,90 (2H, q, J=7,5 Hz), 1,40 is 1.34 (1H, m)of 1.26 (3H, t, J=7.2 Hz), of 0.7 to 0.63 (2H, m)of 0.41 and 0.35 (2H, m).

Example 55

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-1-oxidecoated

Yield 53 mg

Pale yellow powder

1H-NMR (CDCl3) δ: 11,64 (1H, users), 8,44 (1H, DD, J=7,8, and 2.1 Hz), of 8.25 (1H, d, J=6.3 Hz), 7,63-to 7.35 (5H, m)6,91 (1H, d, J=8.7 Hz)and 4.65 (2H, d, J=5.7 Hz), 3,97-3,88 (5H, m), USD 1.43-1,32 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,36 (2H, m).

Example 56

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2,6-dimethoxybenzamide

Yield 46 mg

White powder

1H-NMR (CDCl3) δ: to 7.67 (1H, s), to 7.59 (1H, DD, J=8,4, 1.8 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,30-7,24 (1H, m), 6,92 (1H, d, J=8,4 Hz), 6,56 (2H, d, J=8,4 Hz), 6,24 (1H, users), to 4.62 (2H, DD, J=5,7, and 0.9 Hz), 3.95 to to 3.92 (5H, m), 3,81 (6H, s), 1.41 to to 1.32 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Using of 0.13 g of [2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]methylamine, the compounds of examples 57-59 was obtained in the same manner as in example 1.

Example 57

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methoxypyridine

Yield 24 mg

White powder

1H-NMR (CDCl3) δ: 8,23-8,19 (2H, m), the 7.65 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), 7,51 (1H, d, J=1,8 Hz), 7,43-7,34 (2H, m), 6,92 (1H, d, J=8.7 Hz), 4,60 (2H, d, J=5.4 Hz), 3.96 points-3,93 (8H, m), USD 1.43-of 1.30 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 58

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-solutocapillary

Yield 0.11 g

White powder

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=3,9, 1.8 Hz), 8,17 (1H, users), 7,63 (1H, s), to 7.59 (1H, DD, J=8,4, 1.8 Hz), 7,38-7,31 2H, m), 6,92 (1H, d, J=8,4 Hz), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 3.95 to to 3.92 (5H, m), a-3.84 (2H, d, J=6.3 Hz), measuring 2.20 (1H, cut, J=6.6 Hz), 1,40 is 1.34 (1H, m)of 1.03 (6H, d, J=6.6 Hz), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 59

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-nicotine amide

Yield 71 mg

White powder

1H-NMR (CDCl3) δ: 8,55 (1H, DD, J=7,8, 1.8 Hz), 7,71 (1H, DD, J=7,5, 1.8 Hz), the 7.65 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), 7,17-7,13 (1H, m), 6,93 (2H, d, J=8,4 Hz), 6.35mm (1H, users), 4,58 (2H, DD, J=5,4, and 0.9 Hz), 3.96 points-3,91 (5H, m), 2,69 (3H, s), 1.41 to 1,31 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 60

0.4 g of N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methylsulfonylbenzoyl obtained in example 44 was dissolved in 20 ml of dichloromethane and to the mixture was added to 0.67 g metallocarboranes acid while cooling the solution with ice under stirring. The mixture then was stirred for one hour. The reaction mixture was concentrated under reduced pressure, the residue was purified column chromatography on silica gel (NH silica, n-hexane:ethyl acetate = 1:1) and received 50 mg of white powdery N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methysulfonylmethane.

1H-NMR (CDCl3) δ: 8,11 (1H, DD, J=7,8, and 0.9 Hz), 7,76 (1H, s), 7,69-of 7.55 (4H, m)to 7.50 (1H, d, J=2.1 Hz), 6,93 (1H, d, J=8,4 Hz), 6,50 (1H, users), to 4.62 (2H, d, J=5.4 Hz), 3.95 to 3,90 (5H, m), 3,93-to 3.67 (1H, m), 3,37 (3H, s), 1,40-1,32 (1H, m), 1,27-of 1.18 (3H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 61

0.1 g of N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl is)oxazol-4-ylmethyl]-3-hydroxyphthalimide, obtained in example 45, and 0.16 g of cesium carbonate was dissolved in 4 ml of acetonitrile and to the mixture was added 0.2 g of 1-bromopropane and was stirred over night at room temperature. To the reaction mixture was added water and was carried out by extraction with ethyl acetate. The extract was washed once with water and then washed once with a saturated aqueous solution of citric acid. The organic layer was concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel to obtain 72 mg of white powdery N-2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-propositioned.

1H-NMR (CDCl3) δ: 8,25-to 8.20 (2H, m) to 7.64 (1H, s), 7,60 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,39-to 7.32 (2H, m), 6,92 (1H, d, J=8,4 Hz), to 4.62 (2H, DD, J=5,7, and 0.9 Hz), of 4.05 (2H, t, J=6.6 Hz), 3,94-to 3.92 (5H, m), 1,90 (2H, t, J=7,5, and 6.6 Hz), of 1.40 and 1.33 (1H, m), was 1.04 (3H, t, J=7.5 Hz), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 62

Using 0.18 g of [2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 19, 0.16 g of white powdery N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, DD, J=4,5, 1.8 Hz), 7,63 (1H, s), 7,62-to 7.59 (2H, m), EUR 7.57 (1H, d, J=0.9 Hz), 7,32-7,27 (1H, m), 6,92 (1H, d, J=8,4 Hz), 4,59 (2H, DD, J=6,0, 0.9 Hz), 3,91 (3H, s), 3,86 (2H, d, J=6.9 Hz), was 2.76 (3H, s), measuring 2.20 (1H, cut, J=6,9, and 6.6 Hz), of 1.06 (6H, d, J=6,6 Hz).

Use the 0.15 g of [2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]methylamine, obtained in reference example 19, the compounds of examples 63-75 was obtained in the same manner as in example 1.

Example 63

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxybenzamide

Yield 0.12 g

White powder

1H-NMR (CDCl3) δ: to 8.41 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), to 7.64 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), 7,53 (1H, d, J=2.1 Hz), of 7.48-7,42 (1H, m), 7,11-of 6.90 (3H, m), 4,63 (2H, DD, J=5,4, and 0.9 Hz), of 3.97 (3H, s), 3,91 (3H, C), 3,86 (2H, d, J=6.9 Hz), of 2.21 (1H, cut, J=6,6 Hz)of 1.06 (6H, d, J=6,6 Hz).

Example 64

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methylsulfonylbenzoyl

Yield 0.15 g

White powder

1H-NMR (CDCl3) δ: of 7.69 (1H, s), to 7.61-7,56 (2H, m), 7,51 (1H, d, J=1,8 Hz), 7,45-to 7.15 (3H, m), 6,94-of 6.90 (2H, m), br4.61 (2H, d, J=5.7 Hz), 3,91 (3H, s), 3,85 (2H, d, J=6.9 Hz), the 2.46 (3H, s), measuring 2.20 (1H, cut, J=6.9 Hz), 1.06 a (6H, d, J=6,9 Hz).

Example 65

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-ethoxypyridine

The output 80 mg

White powder

1H-NMR (CDCl3) δ: 8,25 is 8.22 (2H, m), the 7.65 (1H, s), 7,58 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,40-to 7.32 (2H, m), 6,92 (1H, d, J=8,4 Hz), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 4,18 (2H, q, J=6.9 Hz), 3,91 (3H, s), 3,86 (2H, d, J=6.9 Hz), measuring 2.20 (1H, cut, J=6.9 Hz), of 1.52 (3H, t, J=6.9 Hz), of 1.06 (6H, d, J=6,6 Hz).

Example 66

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-methoxy-4-perbenzoic

Yield 0.11 g

White powder

1H-NMR (CDCl3) δ: 8,27-8,21 (2H, m), 7,63 (1H, s), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), 7,52 (1H, d, J=2.1 Hz), 6,93 (1H, d, J=8,4 Hz), for 6.81-6,74 (1H, m), 6,69 (1H, DD, J=10,5, 2.4 Hz), br4.61 (2H, DD,J=5,4, the 0.9 Hz), of 3.96 (3H, s), 3,91 (3H, s), 3,85 (2H, d, J=6.6 Hz), measuring 2.20 (1H, cut, J=6,9, and 6.6 Hz), of 1.06 (6H, d, J=6,6 Hz).

Example 67

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-isopropoxybenzoic

Yield 0.15 g

Colorless oily substance

1H-NMR (CDCl3) δ: 8,64 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), a 7.62 EUR 7.57 (2H, m), 7,54 (1H, d, J=1,8 Hz), 7,44-7,37 (1H, m), 7,08-7,02 (1H, m), 6,98-6,91 (2H, m), 4.72 in (1H, q, J=6.0 Hz), to 4.62 (2H, DD, J=5,1, 0.9 Hz), 3,92 (3H, s), 3,85 (2H, d, J=6.6 Hz), measuring 2.20 (1H, cut, J=6.6 Hz), of 1.40 (6H, d, J=6.0 Hz), of 1.06 (6H, d, J=6,6 Hz).

Example 68

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-fluoro-6-methoxybenzamide

The yield of 0.13 g

White powder

1H-NMR (CDCl3) δ: the 7.65 (1H, d, J=0.9 Hz), 7,58 (1H, DD, J=8,4, and 2.1 Hz), 7,51 (1H, d, J=2.1 Hz), 7,34-7,24 (1H, m), 6,92 (1H, d, J=8,4 Hz), 6,77-6,70 (2H, m), of 6.52 (1H, users), to 4.62 (2H, DD, J=5,7, and 0.9 Hz), 3,91 (3H, s), 3,90-is 3.82 (5H, m), 2,20 (1H, cut, J=6,9 Hz)of 1.06 (6H, d, J=6,9 Hz).

Example 69

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-methoxypyridine

Yield 0.14 g

White powder

1H-NMR (CDCl3) δ: 8,19 is 8.22 (2H, m), the 7.65 (1H, s), 7,58 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=2.1 Hz), 7,43-7,34 (1H, m), 6,92 (1H, d, J=8,4 Hz), br4.61 (2H, DD, J=5,7, and 0.9 Hz), of 3.96 (3H, s), 3,91 (3H, s), 3,86 (2H, d, J=6.6 Hz), measuring 2.20 (1H, cut, J=6,9, and 6.6 Hz), of 1.06 (6H, d, J=6,9 Hz).

Example 70

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-solutocapillary

The yield 68 mg

White powder

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=3,9, and 2.1 Hz), 8,17 (1H, users), to 7.64 (1H, s), 7,58 (1H, DD, J=8,4, and 2.1 Hz), 7,52 (1H, d, J=1,8 Hz), 7,38-7,28 (2H, m), 6,92 (2H, d, J=8,4 Hz), 4,63 (2H, DD, J=5,4, and 0.9 Hz), 3,91 (3H, s), a 3.87-3,82 (4H, m), 2,27 and 2.13 (2H, m), 1,07-1,02 (2H, m).

Example 71

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-propoxybenzene

Exit 75 mg

White powder

1H-NMR (CDCl3) δ: charged 8.52 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,62-7,58 (2H, m), 7,53 (1H, s), 7,42 (1H, TD, J=7,2, 1.8 Hz), 7,06 (1H, t, J=7.8 Hz), 6,95-6,91 (2H, m), to 4.62 (2H, d, J=5,1 Hz)4,06 (2H, t, J=6.6 Hz), 3,94 (3H, s), 3,85 (2H, d, J=6.6 Hz), 2,24-of 2.16 (1H, m), 1.93 and-is 1.81 (2H, m)of 1.06 (6H, d, J=6.6 Hz), of 0.97 (3H, t, J=7.2 Hz).

Example 72

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-butoxybenzene

Yield 47 mg

White powder

1H-NMR (CDCl3) δ: 8,48 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,62-7,58 (2H, m), 7,53 (1H, s), 7,42 (1H, TD, J=7,2, 1.8 Hz), 7,06 (1H, t, J=7.8 Hz), 6,95-6,91 (2H, m), br4.61 (2H, d, J=5,1 Hz), 4,10 (2H, t, J=6.6 Hz), 3,91 (3H, s), 3,85 (2H, d, J=6.6 Hz), 2,24-of 2.16 (1H, m), 1.85 to about 1.75 (2H, m), USD 1.43-of 1.36 (2H, m)of 1.05 (6H, d, J=6.6 Hz), is 0.84 (3H, t, J=7.2 Hz).

Example 73

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-isobutoxide

Yield 90 mg

White powder

1H-NMR (CDCl3) δ: charged 8.52 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,62-7,58 (2H, m), 7,53 (1H, s), 7,42 (1H, TD, J=7,2, 1.8 Hz), 7,06 (1H, t, J=7.8 Hz), 6,93-of 6.90 (2H, m), to 4.62 (2H, d, J=5,1 Hz), 3,91 (3H, s), a 3.87-a 3.83 (4H, m), 2,24-of 2.16 (2H, m)of 1.06 (6H, d, J=6.6 Hz), of 0.95 (6H, d, J=6,6 Hz).

Example 74

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-isopropoxypyridine

Yield 0.11 g

White powder

1H-NMR (CDCl3) δ: charged 8.52 (1H, users), of 8.27 (1H, users), 7,63 (1H, s), 7,58 (1H, DD, J=7,8, 1.8 Hz),7,53 (1H, C), 7,35-7,34 (2H, m), 6,92 (1H, d, J=8,4 Hz), 4,67-br4.61 (3H, m), 3,91 (3H, s), 3,85 (2H, d, J=6.6 Hz), 2,22-2,17 (1H, m)of 1.42 (6H, d, J=6.6 Hz), of 1.06 (6H, d, J=6,6 Hz).

Example 75

N-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-nicotine amide

The yield of 0.13 g

White powder

1H-NMR (CDCl3) δ: charged 8.52 (1H, users), 7,86 (1H, d, J=7.5 Hz), 7,76 (1H, d, J=7.5 Hz), 7,69 (1H, s), to 7.59 (1H, d, J=4, 2 Hz), 7,56 (1H, s), 6,92 (1H, d, J=8.7 Hz), 4,58 (2H, d, J=5,1 Hz), 3,91 (3H, s), a-3.84 (2H, d, J=6,9 Hz), 2,69 (3H, s), 2,23-to 2.15 (1H, m)of 1.05 (6H, d, J=5,1 Hz).

Example 76

Using 0.2 g of {2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}methylamine obtained in reference example 25, 0.24 g of white powdery N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-3-methoxypyridine was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,24-8,19 (2H, m), 7,72 (1H, DD, J=8,4, 1.8 Hz), the 7.65 (1H, d, J=0.9 Hz), a 7.62 (1H, d, J=1,8 Hz), 7,43-to 7.35 (2H, m), 6,98 (1H, d, J=8,4 Hz), 4,60 (2H, DD, J=5,7, and 0.9 Hz), to 4.46 (2H, q, J=5.4 Hz), 3,95 (3H with), 3,93 (3H, s).

Using 0.2 g of {2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}methylamine obtained in reference example 25, the compounds of examples 77-79 was obtained in the same manner as in example 1.

Example 77

N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-3-ethoxypyridine

Yield 0.24 g

White powder

1H-NMR (CDCl3) δ: compared to 8.26 is 8.22 (2H, m), 7,72 (1H, DD, J=8,4, and 2.1 Hz), the 7.65 (1H, s), 7,63 (1H, d, J=1,8 Hz), 7,40-to 7.32 (2H, m), 6,98 (1H, d, J=8.1 Hz), to 4.62 (2H, DD, J=5,7, and 0.9 Hz), to 4.46 (2H, q, J=8,4 Hz), 18 (2H, kV, J=6.9 Hz), of 1.52 (3H, t, J=6.9 Hz).

Example 78

N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-methoxybenzamide

Yield 0.18 g

White powder

1H-NMR (CDCl3) δ: 8,42 (1H, users), 8,23 (1H, DD, J=7,5, 1.8 Hz), 7,73 (1H, DD, J=8,4, and 2.1 Hz), 7,65-of 7.60 (2H, m), of 7.48-7,42 (1H, m), was 7.08 (1H, dt, J=8,4, and 0.9 Hz), 6,98 (1H, d, J=8,4 Hz), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 4,46 (2H, kV, J=8,4 Hz), 3,98 (3H, s), 3,93 (3H, s).

Example 79

N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-methylbenzamide

Yield 0.15 g

White powder

1H-NMR (CDCl3) δ: 7,72 (1H, DD, J=8,4, and 2.1 Hz), 7,66 (1H, s), to 7.61 (1H, d, J=2.1 Hz), 7,41-7,14 (4H, m), 6,98 (1H, d, J=8,4 Hz), of 6.31 (1H, users), 4,58 (2H, DD, J=5,4, and 0.9 Hz), of 4.45 (2H, q, J=8,4 Hz), 3,93 (3H, s), 2,46 (3H with).

Using 0.15 g of {2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}methylamine obtained reference example 25, the compounds of examples 80-82 was obtained in the same manner as in example 1.

Example 80

N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-propoxybenzene

Yield 0.15 g

White powder

1H-NMR (CDCl3) δ: 8,53 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,73 (1H, DD, J=8,4, and 2.1 Hz), 7,65-of 7.60 (2H, m), 7,45-7,38 (1H, m), 7,09-6,93 (3H, m), to 4.62 (2H, d, J=5,1 Hz), of 4.45 (2H, q, J=8.1 Hz), 4,07 (2H, t, J=6,6 Hz), of 3.94 (3H, s), a 1.88 (2H, cut, J=7,5, and 6.6 Hz), and 0.98 (3H, t, J=7.5 Hz).

Example 81

N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-isopropoxybenzoic

Yield 0.18 g

White powder

1H-NMR (CDCl3) δ: ,64 (1H, users), 8,23 (1H, d is, J=7,8, 1.8 Hz), 7,74 (1H, DD, J=8,4, and 2.1 Hz), the 7.65 (1H, d, J=2.1 Hz), 7,63 (1H, s), 7,44-7,37 (1H, m), 7,08-6,94 (3H, m), to 4.73 (1H, TT, J=6.0 Hz), to 4.62 (2H, DD, J=5,1, 0.9 Hz), to 4.46 (2H, q, J=8,4 Hz), of 3.94 (3H, C)of 1.41 (6H, d, J=6.0 Hz).

Example 82

N-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-4-chloro-2-methoxybenzamide

Yield 0.21 g

White powder

1H-NMR (CDCl3) δ: 8,29 (1H, users), 8,17 (1H, d, J=8,4 Hz), 7,73 (1H, DD, J=8,4, 1.8 Hz), to 7.64 (1H, d, J=1.5 Hz), 7,07 (1H, DD, J=8,4, 1.8 Hz), 7,00-of 6.96 (2H, m), 4,60 (2H, DD, J=5,4, and 0.9 Hz), to 4.46 (2H, q, J=8,4 Hz), 3,98 (3H with), 3,93 (3H, s).

Example 83

Using 0.1 g of {2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-yl}methylamine obtained in reference example 34, 0.11 g of white powdery N-{2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-ethoxybenzene was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,54 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz) to 7.64 (1H, s), 7,60-of 7.55 (2H, m), 7,45-7,38 (1H, m), 7,10? 7.04 baby mortality (2H, m)6,94 (1H, d, J=8.1 Hz), to 4.62 (2H, DD, J=5,4, and 0.9 Hz), 4,48 (2H, q, J=8,4 Hz), 4,18 (2H, kV, J=6.9 Hz), 3,95 (2H, d, J=7,2 Hz), to 1.48 (3H, t, J=7.2 Hz), 1,35-of 1.29 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 84

Using 0.18 g {2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-yl}methylamine obtained in reference example 34, 0.2 g of white powdery N-{2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-3-methylphthalimide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ:to 8.57 (1H, users), 8,39 (1H, DD, J=4,5, 1.2 Hz), to 7.64 (1H, s), 7,60-of 7.55 (3H, m), 7,32-7,26 (1H, m), 7,06-7,03 (1H, m), 4,59 (2H, DD, J=5,7, and 0.9 Hz), 4,48 (2H, q, J=8,4 Hz), 3,95 (2H, d, J=6.9 Hz), was 2.76 (3H, s), 1,38 of 1.28 (1H, m), 0,69-of 0.62 (2H, m), and 0.40 and 0.35 (2H, m).

Example 85

Using 0.3 g of [2-(3,4-dioxyphenyl)oxazol-4-yl]methylamine obtained in reference example 37, 0.11 g of white powdery N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-2-propoxybenzene was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,51 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,60 is 7.50 (3H, m), 7,41 (1H, m), 7,06 (1H, m), 7,00-of 6.90 (2H, m), br4.61 (2H, d, J=5,1 Hz)4,06 (2H, t, J=6.6 Hz), to 1.87 (2H, TCEs., J=7,2, and 6.6 Hz), for 1.49 (6H, t, J=6.9 Hz), is 0.96 (3H, t, J=7.2 Hz).

Using 0.3 g of [2-(3,4-dioxyphenyl)oxazol-4-yl]methylamine obtained in reference example 37, the compounds of examples 86-91 was obtained in the same manner as in example 1.

Example 86

N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane

Yield 0.11 g

White powder

1H-NMR (CDCl3) δ: 7,75 is 7.50 (7H, m)6,91 (1H, d, J=8,4 Hz), 6,32 (1H, users), 4,59 (2H, d, J=5.4 Hz), 4,17 (2H, q, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), to 1.48 (6H, t, J=6.9 Hz).

Example 87

N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]picolinate

Yield 0.34 g

White powder

1H-NMR (CDCl3) δ: 8,55 (1H, m), of 8.47 (1H, users), 8,21 (1H, d, J=7.8 Hz), the 7.85 (1H, m), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), 7,55 (1H, d, J=1,8 Hz), 7,42 (1H, m)6,91 (1H, d, J=8,4 Hz), 6,32 (1H, users), 4,63 (2H, d, J=6.0 Hz), 4,18 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz).

N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene

The output of 0.23 g

White powder

1H-NMR (CDCl3) δ: 8,55 (1H, m), of 8.47 (1H, users), 8,21 (1H, d, J=7.8 Hz), the 7.85 (1H, m), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), 7,55 (1H, d, J=1,8 Hz), 7,42 (1H, m)6,91 (1H, d, J=8,4 Hz), 6,32 (1H, users), 4,63 (2H, d, J=6.0 Hz), 4,18 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz).

Example 89

N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-4-ethoxybenzene

Yield 0.32 g

White powder

1H-NMR (CDCl3) δ: 7,80-of 7.70 (2H, m), 7,63 (1H, s), 7,60 is 7.50 (2H, m), 6,95-6,85 (3H, m), of 6.66 (1H, users), of 4.57 (2H, q, J=6.0 Hz), 4,17 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), 4,06 (2H, q, J=6.9 Hz), to 1.48 (3H, t, J=6,9 Hz)to 1.48 (3H, t, J=6.9 Hz), of 1.42 (3H, t, J=6.9 Hz).

Example 90

N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-5-methoxy-2-cryptomaterial

Yield 0.34 g

White powder

1H-NMR (CDCl3) δ: of 7.95 (1H, users), 7,73 (1H, d, J=3.0 Hz), 7,70-to 7.50 (3H, m), of 6.99 (1H, DD, J=9,0, 3.0 Hz), 6.90 to-to 6.80 (2H, m), br4.61 (2H, d, J=6.0 Hz), 4,18 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), 3,82 (3H, s)to 1.48 (3H, t, J=6.9 Hz), of 1.46 (3H, t, J=6.9 Hz).

Example 91

N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-3-ethoxybenzene

Yield 0.12 g

White powder

1H-NMR (CDCl3) δ: EUR 7.57 (1H, DD, J=8,1, 2,1 Hz), 7,53 (1H, d, J=2.1 Hz), 7,35-of 7.25 (3H, m), 7,01 (1H, m), 6,92 (1H, d, J=8.1 Hz), of 6.68 (1H, users), 4,58 (2H, d, J=5.4 Hz), 4,18 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), 4,07 (2H, q, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz), of 1.42 (3H, t, J=6.9 Hz).

Example 92

Using 0.3 g of [2-(3,4-acid)oxazol-4-yl]METI the amine, obtained in reference example 40, 0.27 g of white powdery N-[2-(3,4-acid)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=8,1, 1.8 Hz), 7,65-of 7.60 (2H, m), 7,55 (1H, d, J=1.5 Hz), 7,42 (1H, m), 7,07 (1H, m), 6,95-of 6.90 (2H, m), 4,63 (2H, d, J=5,1 Hz), 4,18 (2H, q, J=6.9 Hz), 3,98 (3H, s), 3,97 (3H, s)of 1.26 (3H, t, J=6.9 Hz).

Example 93

Using 0.25 g of [2-(3,4-acid)oxazol-4-yl]methylamine obtained in reference example 40, to 0.23 g of white powdery N-[2-(3,4-acid)oxazol-4-ylmethyl]-2-ethylbenzamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 7,66 (1H, s), 7,60 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,40-7,20 (4H, m), 6,93 (1H, d, J=8,4 Hz), 6,34 (1H, users), 4,58 (2H, d, J=5.4 Hz), of 3.96 (3H, s), of 3.94 (3H, s), 2,82 (2H, q, J=7.5 Hz,), of 1.20 (3H, t, J=7.5 Hz).

Example 94

Using 0.2 g of [2-(3,4-acid)oxazol-4-yl]methylamine obtained in reference example 40, 0.16 g of white powdery N-[2-(3,4-acid)oxazol-4-ylmethyl]-3-methylphthalimide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, m), 7,65-of 7.55 (4H, m), 7,30 (1H, m), 6,92 (1H, d, J=8,4 Hz), 4,59 (2H, d, J=6.0 Hz), of 3.97 (3H, s), 3,93 (3H, s), was 2.76 (3H, s), 1,58 (3H, s).

Example 95

Using 0.2 g of [2-(3,4-acid)oxazol-4-yl]methylamine obtained in reference example 40, 0.12 g of white powdery N-[2-(3,4-acid)oxazol-4-ylmethyl]3-methoxypyridine was obtained in the same way, as in example 1.

1H-NMR (CDCl3) δ: 8,21 (1H, users), to 8.20 (1H, DD, J=3,9, 1.8 Hz), the 7.65 (1H, s), to 7.61 (1H, DD, J=8,4, 1.8 Hz), 7,54 (1H, d, J=1,8 Hz), 7,45-7,30 (2H, m), 6,92 (1H, d, J=8,4 Hz), br4.61 (2H, d, J=6.0 Hz), of 3.97 (3H, s), of 3.96 (3H with), 3,93 (3H, s).

Example 96

of 0.13 g of [2-(3-benzyloxy-4-deformational)oxazol-4-yl]methylamine obtained in reference example 46, suspended in 10 ml of acetone. Then to the resulting suspension was added 0.14 g of 1-hydroxybenzotriazole, to 0.19 g of the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 0.14 g of 3-methylpyridine and the mixture is boiled under reflux for 30 minutes. The reaction mixture was concentrated under reduced pressure and to the residue was added water. Was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated. The residue was purified column chromatography on silica gel(n-hexane:ethyl acetate = 1:1) to obtain 0.16 g of white powdery N-[2-(3-benzyloxy-4-deformational)oxazol-4-ylmethyl]-3-methylphthalimide.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,40 (1H, d, J=3,9 Hz), 7,74-7,58 (4H, m), 7,47-of 7.23 (7H, m), 6,62 (1H, t, J=74,7 Hz), to 5.21 (2H, s), 4,60 (2H, d, J=5.7 Hz), was 2.76 (3H, s).

Example 97

0.16 g of N-[2-(3-benzyloxy-4-deformational)oxazol-4-ylmethyl]-3-methylphthalimide obtained in example 96 was dissolved in 5 ml of ethanol to the mixture was added 20 mg of 10% palladium-on-carbon in powder form and the mixture was stirred at room temp is the temperature for 30 minutes in hydrogen atmosphere. The catalyst was filtered and the filtrate was concentrated to obtain 0.12 g of white powdery N-[2-(4-deformedarse-3-hydroxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide.

1H-NMR (CDCl3) δ: 8,60-8,54 (1H, m), 8,39 (1H, d, J=3.3 Hz), 7,69-of 7.55 (4H, m), 7,37-7,28 (1H, m), 7,18 (1H, d, J=8,4 Hz), 6,59 (1H, t, J=73,2 Hz), 5,79 (1H, users), 4,59 (2H, DD, J=6,0, 0.9 Hz), was 2.76 (3H, s).

Example 98

0.12 g of N-[2-(4-deformedarse-3-hydroxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide obtained in example 97, and 0.15 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 4 ml of ethanol. To the mixture was added 0.15 ml (methyl bromide)cyclopropane and was heated at the boil under reflux for 3 hours. The solvent drove by distillation and the residue was added water. Was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 1:1). The crude crystals was recrystallized using a mixture of ethanol-n-hexane and received 60 mg of white powdery N-[2-(3-cyclopropylmethoxy-4-deformational)oxazol-4-ylmethyl]-3-methylphthalimide.

1H-NMR (CDCl3) δ: 8,59-8,54 (1H, m), 8,39 (1H, DD, J=4,5, 1.2 Hz), to 7.67 (1H, s), 7,63-7,56 (3H, m), 7,37-7,28 (1H, m), 7,22 (1H, d, J=8.1 Hz), 6,69 (1H, t, J=75,0 Hz), 4,59 (2H, DD, J=5,7, and 0.9 Hz), 3,98 (2H, d, J=6,9 Hz)that was 2.76 (3H, s), 1,35-1,20 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 99

Using 0.2 g of [2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]methylamine obtained in reference example 13, 0.11 g of white powdery N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]isoquinoline-1-carboxamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 9,60 (1H, m), 8,67 (1H, users), of 8.47 (1H, d, J=2.4 Hz), of 7.90-7,80 (2H, m), 7,75-the 7.65 (3H, m), to 7.61 (1H, DD, J =8,4, 1.8 Hz), 7,53 (1H, d, J=1,8 Hz), 6,92 (1H, d, J=8,4 Hz), and 4.68 (2H, d, J=6.0 Hz), of 3.94 (2H,, d, J=7.5 Hz), to 3.92 (3H, s)of 1.39 (1H, m), 0.70 to to 0.60 (2H, m), and 0.40 and 0.35 (2H, m).

Example 100

4.42 g of sodium hydroxide suspended in 160 ml of dimethoxyethane. The suspension was stirred under ice cooling while simultaneously separate addition of 16 g of 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]methylpropionate obtained in reference example 48, and 39,23 g 2-ethoxypyrazine acid and then was carried out by heating and boiling under reflux for 7 hours. After cooling with ice to the mixture was added a saturated solution of ammonium chloride and was stirred for 30 minutes. Then to the mixture was added water and was carried out by extraction with ethyl acetate, and then dried over anhydrous magnesium sulfate and the solvent is then drove away. The residue was subjected to purification on a column of silica gel (n-hexane:ethyl acetate = 3:1) and received a 13.4 g of a yellow oily substance, methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(2-detoxif the Nile)-3-oxopropionate.

1H-NMR (CDCl3) δ: 7,71 (1H, d, J=7.8 Hz), EUR 7.57-rate of 7.54 (3H, m), of 7.48-7,28 (6H, m), 6,99-of 6.90 (3H, m), 5,16 (2H, s), to 4.98 (1H, t, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), 3,91 (3H, s), 3,70 (3H, s), 3.27 to 3,19 (2H, m)of 1.45 (3H, t, J=6.9 Hz).

Example 101

of 13.4 g of methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(2-ethoxyphenyl)-3-oxopropionate obtained in example 100, suspended in 67 ml of ethanol to the mixture was added 67 ml of 47%Hydrobromic acid and the suspension was heated and boiled under reflux during the night. The mixture was left to cool and then the resulting crystals were collected through filtration, washed with water and diisopropyl ether and dried to obtain, thus, of 8.1 g of a white powder of 1-(2-ethoxyphenyl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-it.

1H-NMR (CDCl3) δ: 8,30 (1H, d, J=8.7 Hz), to 7.84 (1H, d, J=1,8 Hz), 7,83-7,71 (2H, m), 7,45 (1H, t, J=8,4 Hz), 7,06 (1H, d, J=8.7 Hz), 6,99-6,93 (2H, m)to 4.17 (2H, q, J=6.9 Hz), of 4.00 (3H, s)to 3.67 (2H, t, J=6.6 Hz), the 3.35 (2H, t, J=6.6 Hz), of 1.55 (3H, t, J=6.9 Hz).

Example 102

of 8.1 g of 1-(2-ethoxyphenyl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she obtained in example 101, suspended in 220 ml of ethanol, to the mixture was added 10 g of 1,8-diazabicyclo[5.4.0]undec-7-ene and 5,96 g (methyl bromide)cyclopropane and was carried out by stirring for 5 hours while heating and boiling under reflux. After distillation of the ethanol under reduced pressure was added to the control, was carried out by extraction with ethyl acetate, and then dried over anhydrous magnesium sulfate and drove the solvent. The residue was subjected to purification on a column of silica gel (n-hexane:ethyl acetate = 4:1) and the crude crystals are recrystallized from ethanol to obtain, thus, 4.4 g of white powdery 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,56 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, s), 7,45-7,39 (2H, m), 7,00-6,89 (3H, m), of 4.13 (2H, q, J=7.2 Hz), 3,93-3,91 (5H, m)to 3.41 (2H, t, J=6.6 Hz), 2,99 (2H, t, J=6,6 Hz)and 1.51 (3H, t, J=7.2 Hz), 1,47 (1H, m), 0.67 and-of 0.64 (2H, m), 0,40-0,36 (2H, m).

Example 103

0.3 g of 1-(2-ethoxyphenyl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she obtained in example 101, suspended in 10 ml of ethanol to the mixture was added to 0.37 g of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.26 g of ethyliodide and the suspension was stirred for 4 hours while heating and boiling under reflux. After distillation of the ethanol under reduced pressure was added water, was carried out by extraction with ethyl acetate, and then dried over anhydrous magnesium sulfate and drove the solvent. The residue was subjected to purification on a column of silica gel (n-hexane:ethyl acetate = 3:1) obtaining, thus, 0.15 g of white powdery 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he is.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,56 (1H, DD, J=8,4, 1.8 Hz), 7,52-7,40 (2H, m), 6,99-6,89 (3H, m), is 4.21-4.09 to (4H, m), 3,91 (3H, s), 3,42 (2H, t, J=6.9 Hz), 2,99 (2H, t, J=6.9 Hz), 1,51-of 1.45 (6H, m).

Example 104

0.3 g of 1-(2-ethoxyphenyl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she obtained in example 101, suspended in 10 ml of ethanol to the mixture was added to 0.37 g of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.14 ml of allylbromide and was carried out by stirring for 3 hours while heating and boiling under reflux. After distillation of the ethanol under reduced pressure was added water, was carried out by extraction with ethyl acetate, and then dried over anhydrous magnesium sulfate and drove the solvent. The residue was subjected to purification on a column of silica gel (n-hexane:ethyl acetate = 3:1) obtaining, thus, 0.2 g of white powdery 3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), 7,58 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,45-7,40 (2H, m), 7,00-of 6.90 (3H, m), 6,18-6,05 (1H, m), 5,47-of 5.29 (2H, m), of 4.67 (2H, d, J=5,1 Hz), of 4.13 (2H, q, J=6,9 Hz), to 3.92 (3H, s), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), of 1.47 (3H, t, J=6.9 Hz).

Using 1-(2-ethoxyphenyl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-he obtained in example 101, the compounds of examples 105-110 was obtained in the same manner as in example 102.

Example 105

3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-the l]-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57-7,51 (2H, m), 7,45-7,39 (2H, m), 6,99-to 6.88 (3H, m), 4,88 (1H, users), of 4.12 (2H, q, J=6.9 Hz), 3,88 (3H, s), 3,42 (2H, t, J=6.9 Hz), 2,99 (2H, t, J=6.9 Hz), 2,04-to 1.87 (6H, m), 1,65-to 1.60 (2H, m)of 1.47 (3H, t, J=6.9 Hz).

Example 106

3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,55 (1H, DD, J=8,4, 1.8 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,45-7,40 (2H, m), of 4.13 (2H, q, J=6.9 Hz), 3,90 (3H, s), a-3.84 (2H, d, J=6.9 Hz), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7,2 Hz), 2,23 with 2.14 (1H, m)to 1.48 (3H, t, J=6.9 Hz), of 1.05 (6H, d, J=6,9 Hz).

Example 107

1-(2-ethoxyphenyl)-3-[2-(4-methoxy-3-propoxyphenyl)oxazol-4-yl]propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,56 (1H, DD, J=8,1, 1.8 Hz), 7,52 (1H, s), 7,45-7,40 (2H, m), 7,00-6,89 (3H, m), of 4.13 (2H, q, J=6.9 Hz), of 4.05 (2H, t, J=6.9 Hz), 3,90 (3H, s), 3,42 (2H, t, J=7.5 Hz), 3,00 (2H, t, J=7.5 Hz), 1,95-of 1.84 (2H, m)of 1.47 (3H, t, J=6.9 Hz), of 1.05 (3H, t, J=6.9 Hz).

Example 108

3-[2-(3-(3-butenyloxy)-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, s), 7,45-7,40 (2H, m), 6,97-6,89 (3H, m), 6,00-5,90 (1H, m), 5,22-5,10 (2H, m), 4,17-4,11 (4H, m), 3,90 (3H, s), 3,42 (2H, t, J=7.5 Hz,), to 3.00 (2H, t, J=7.5 Hz), 2,67-2,62 (2H, m)of 1.47 (3H, t, J=6.9 Hz).

Example 109

3-[2-(3-butoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), 7,53 (1H, d, J=2.1 Hz), 7,45-7,39 (2H, m), 7,00-6,89 (3H, m), 4,16-4,07 (4H, m), 3,98 (3H, s), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7,2 Hz), 1,90-to 1.86 (2H, m), 1,57-of 1.42 (5H, m), 99 (3H, t, J=7.2 Hz).

Example 110

1-(2-ethoxyphenyl)-3-[2-(4-methoxy-3-(2-propenyloxy)phenyl)oxazol-4-yl]propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), 7,66-7,63 (2H, m), 7,46-7,39 (2H, m), 7,00-6,92 (3H, m), a 4.83 (2H, d, J=2.1 Hz), of 4.13 (2H, q, J=6.9 Hz), to 3.92 (3H, s), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), 2,52 (1H, t, J=2.1 Hz), of 1.47 (3H, t, J=6.9 Hz).

Example 111

5.0 g of 1-(2-ethoxyphenyl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she obtained in example 101, was dissolved in 50 ml of dimethylformamide, to the mixture was added to 3.35 g of 2-bromopropane and 5.63 g of potassium carbonate and was carried out by stirring overnight at room temperature. To the mixture was added water, was carried out by extraction with ethyl acetate, and then dried over anhydrous magnesium sulfate and drove the solvent. The residue was subjected to purification on a column of silica gel (n-hexane:ethyl acetate = 4:1) and the crude crystals are recrystallized from ethanol to obtain, thus, 2,99 g of a white powder of 1-(2-ethoxyphenyl)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), to 7.59-rate of 7.54 (2H, m), 7,45-7,39 (2H, m), 7,00-6,89 (3H, m), 4,68-4,60 (1H, m), of 4.13 (2H, q, J=6.9 Hz), with 3.89 (3H, s), 3,42 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), 1,47 (3H, t, J=6.9 Hz), of 1.39 (6H, d, J=6.3 Hz).

Using 1-(2-ethoxyphenyl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-he obtained in example 101, the compounds of examples 112-122 who was lucali in the same way, as in example 111.

Example 112

1-(2-ethoxyphenyl)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propane-1-he

1H-NMR (CDCl3) δ: 7,72-to 7.68 (2H, m), 7,60 (1H, d, J=1,8 Hz), 7,45-7,39 (2H, m), 7,00-6,92 (3H, m), of 4.44 (2H, q, J=8,4 Hz), of 4.13 (2H, q, J=6.6 Hz), 3,90 (3H, s), 3,42 (2H, t, J=6.9 Hz), 2,99 (2H, t, J=6.9 Hz), to 1.48 (3H, t, J=6.6 Hz).

Example 113

3-[2-(3-cyclohexylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,55 (1H, DD, J=8,4, 1.8 Hz), to 7.50 (1H, d, J=1,8 Hz), 7,45-7,40 (2H, m), 7,00-to 6.88 (3H, m), 4,14 (2H, q, J=6.9 Hz), 3,90 (3H, s), 3,86 (2H, d, J=6.0 Hz), 3,42 (2H, t, J=7,2 Hz), 2,99 (2H, t, J=7.2 Hz), 2.00 in to 1.86 (3H, m), 1,79-and 1.63 (3H, m)of 1.45 (3H, t, J=6.9 Hz), 1,40-1,22 (2H, m), 1,10-1,02 (2H, m).

Example 114

3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,55 (1H, DD, J=8,4, 1.8 Hz), to 7.50 (1H, d, J=1,8 Hz), 7,45-7,40 (2H, m), 7,00-to 6.88 (3H, m), 4,14 (2H, q, J=6.9 Hz), 3,95 (2H, d, J=7,2 Hz), 3,90 (3H, s), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2,48 is 2.44 (1H, m), 2,04 is 1.86 (2H, m), 1,63 of 1.50 (4H, m)of 1.45 (3H, s), of 1.39 and 1.35 (2H, m).

Example 115

1-(2-ethoxyphenyl)-3-[2-(4-methoxy-3-(4-pentyloxy)phenyl)oxazol-4-yl]propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, and 2.1 Hz), 7,56 (1H, DD, J=8,1, 2,1 Hz), 7,51 (1H, d, J=2.1 Hz), 7,45-7,39 (2H, m), 7,00-6,89 (3H, m), by 5.87-of 5.81 (1H, m), 5,10-4,99 (2H, m), 4,17-4,08 (4H, m), 3,91 (3H, s), 3,42 (2H, t, J=7,2 Hz), 2,99 (2H, t, J=7.2 Hz), 2,27-2,22 (2H, m), 2,04-of 1.95 (2H, m)of 1.47 (3H, t, J=7.2 Hz).

Example 116

3-[2-(3-cyclobutylmethyl-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)is ropan-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, and 2.1 Hz), 7,56 (1H, DD, J=8,1, 2,1 Hz), 7,51 (1H, d, J=2.1 Hz), 7,45-7,39 (2H, m), 7,00-to 6.80 (3H, m), of 4.13 (2H, q, J=7.2 Hz), 4,07 (2H, d, J=7,2 Hz), 3,90 (3H, s), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2,96-to 2.85 (1H, m), 2,20-and 2.14 (2H, m), 1.91 a and 1.80 (2H, m)of 1.45 (3H, t, J=7.2 Hz).

Example 117

1-(2-ethoxyphenyl)-3-{2-[4-methoxy-3-(3-methyl-2-butenyloxy)phenyl]oxazol-4-yl}propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57 (1H, DD, J=8,1, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,00-6,89 (3H, m), of 5.55 (1H, t, J=6.6 Hz), with 4.64 (2H, d, J=6.6 Hz), of 4.13 (2H, q, J=6.9 Hz), 3,91 (3H, s), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 1.77 in (6H, d, J=6.6 Hz), a 1.45 (3H, t, J=6.9 Hz).

Example 118

3-{2-[3-(2-cyclohexyloxy)-4-methoxyphenyl]oxazol-4-yl}-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,60-EUR 7.57 (2H, m), 7,42-7,39 (2H, m), 7,00-6,89 (3H, m), 6,00-of 5.92 (2H, m), 4,88 (1H, users), is 4.15 (2H, q, J=7.2 Hz), with 3.89 (3H, s), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7,2 Hz), 2,04 and 1.80 (4H, m), 1,72-of 1.53 (2H, m)of 1.45 (3H, t, J=7.2 Hz).

Example 119

1-(2-ethoxyphenyl)-3-[2-(4-methoxy-3-penetrometer)oxazol-4-yl]propane-1-he

1H-NMR (CDCl3) δ: of 7.69 (1H, DD, J=7,8, 1.8 Hz), to 7.59 (1H, DD, J=8,4, 1.8 Hz), 7,56 (1H, d, J=1,8 Hz), 7,51-6,98 (7H, m), 6,95-of 6.90 (3H, m), 4,27 (2H, t, J=7.2 Hz), 4,11 (2H, q, J=6.9 Hz), 3,91 (3H, s)to 3.41 (2H, t, J=7,2 Hz), 3,20 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7,2 Hz), and 1.54 (3H, t, J=6.9 Hz).

Example 120

1-(2-ethoxyphenyl)-3-{2-[4-methoxy-3-(3-phenylpropoxy)phenyl]oxazol-4-yl}propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,58 (1H, DD, J=8,4, 1.8 Hz), 7,56 (1H, d, J=1,8 Hz), 7,49-7,39 (2H, m), 7,30-to 7.15 (5H, m), 6,99-6,90(3H, m), 4,16-4,08 (4H, m)to 3.92 (3H, s), 3,42 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), 2,84 (2H, t, J=8.1 Hz), 2,24-of 2.15 (2H, m)of 1.46 (3H, t, J=6.9 Hz).

Example 121

3-{2-[3-(2-cyclopropylmethoxy)-4-methoxyphenyl]oxazol-4-yl}-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57-of 7.55 (2H, m), 7,43-7,39 (2H, m), 7,00-6,89 (3H, m), 4,19-4,10 (4H, m), 3,91 (3H, s), 3,42 (2H, t, J=6.9 Hz), a 3.01 (2H, t, J=6.9 Hz), 1,81-of 1.74 (2H, m)to 1.48 (3H, t, J=6,9 Hz), 0.88 to 0,83 (1H, m), 0,52 of 0.47 (2H, m), of 0.16 and 0.12 (2H, m).

Example 122

3-{2-[3-(2-cyclopentyloxy)-4-methoxyphenyl]oxazol-4-yl}-1-(2-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), 7,56 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=2.1 Hz), 7,45-7,39 (2H, m), 7,00-6,89 (3H, m), 4,17-4,07 (4H, m), 3,90 (3H, s), 3,42 (2H, t, J=6,9 Hz)of 3.00 (2H, t, J=6,9 Hz), 2,00-of 1.81 (5H, m), 1,66-of 1.62 (4H, m)of 1.45 (3H, t, J=6.9 Hz), 1,28-of 1.15 (2H, m).

Example 123

1.0 g of methyl 3-{2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propionate obtained in reference example 49, and 0.54 g of methyl 3-methoxypyridine was added to 5 ml of dimethylformamide and the mixture was stirred under ice cooling for 10 minutes. To the mixture was added 0,83 g of tert-pentoxide, sodium, and then stirred under ice cooling for one hour, followed by stirring at room temperature for 1 hour. The reaction mixture was stirred under ice cooling, to the mixture was added a saturated solution of ammonium chloride and was again stirred for 30 minutes. To the mixture was added water, carried and extraction with ethyl acetate, and then was dried over anhydrous magnesium sulfate and drove the solvent. To the residue was added 5.0 ml of dimethyl sulfoxide, 84 mg of lithium chloride and 41 μl of distilled water and the mixture was stirred under heating at 110°C over night. The mixture was left to cool and then to the mixture was added water, was carried out by extraction with ethyl acetate, and then dried over anhydrous magnesium sulfate and drove the solvent. The obtained residue was subjected to purification on a column of silica gel (n-hexane:ethyl acetate = 4:1) and the crude crystals are recrystallized from a mixture of ethyl acetate and diisopropyl ether to obtain, thus, 0.11 g of white powdery 3-{2-[3-cyclopropylmethoxy-4-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-1-(3-methoxypyridine-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,24 (1H, d, J=4, 2 Hz), 7,55-7,47 (2H, m), the 7.43 (1H, s), 7,40-to 7.35 (2H, m), 7,03 (1H, d, J=8,4 Hz), to 4.46 (2H, q, J=7.2 Hz), of 3.94 (2H, d, J=6.6 Hz), 3,90 (3H, s), 3,51 (2H, d, J=7,2 Hz), 3,01 (2H, d, J=7,2 Hz), 1,31-of 1.26 (1H, m), 0,68-of 0.62 (2H, m), 0,39-0,34 (2H, m).

Example 124

2 g of methyl 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]propionate obtained in reference example 48, and 1.1 g of methyl 3-methoxypyridine was dissolved in 10 ml of dimethylformamide while stirring under ice cooling to the mixture was added of 1.81 g of a solution of tert-pentoxide, sodium, and was stirred for 30 minutes. The mixture was again stirred in t is the treatment for 5 hours at room temperature, to the reaction mixture were added ice followed by the addition of saturated aqueous solution of ammonium chloride and continued stirring the mixture. After stirring the reaction mixture for 30 minutes, to the mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 1:1) obtaining, thus, 1.55 g of white amorphous methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(3-methoxypyridine-2-yl)-3-oxopropionate.

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=4,5, 1.8 Hz), EUR 7.57-7,28 (10H, m)6,91 (1H, d, J=9.0 Hz), 5,18-5,13 (3H, m), 3,91-are 3.90 (6H, m)to 3.64 (3H, s), 3,36-3,18 (2H, m).

Example 125

1.5 g of methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(3-methoxypyridine-2-yl)-3-oxopropionate obtained in example 124, was dissolved in 22.5 ml of ethanol to the mixture was added 7.5 ml of 47%Hydrobromic acid and the mixture was stirred under heating at 80°C for 7.5 hours. While stirring under ice cooling, the reaction mixture was neutralized using 5N. the sodium hydroxide solution and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated under reduced pressure and the obtained residue was purified column of chromatography the th on silica gel (dichloromethane:methanol = 20:1) to obtain, thus, 0.65 g of pale yellow oily substance, 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-3-(3-methoxypyridine-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=7,2, 1.5 Hz), 7,55-7,27 (5H, m), to 6.88 (1H, d, J=8.7 Hz), 5,72 (1H, s), 3,92-to 3.89 (6H, m), 3,51 (2H, t, J=7.5 Hz), 3,03 (2H, t, J=7.5 Hz).

Example 126

Using 0.24 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-3-(3-methoxypyridine-2-yl)propane-1-she obtained in example 125, 0.11 g of white powdery 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-3-(3-methoxypyridine-2-yl)propane-1-she's got in the same way as in example 102.

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=4.2, and 1.2 Hz), to 7.59-to 7.32 (5H, m)6,91 (1H, d, J=8,4 Hz), 3,94-are 3.90 (8H, m), 3,51 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), 1,40-of 1.30 (1H, m), 0,69-of 0.62 (2H, m), 0,41-0,35 (2H, m).

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-3-(3-methoxypyridine-2-yl)propane-1-he obtained in example 125, the compounds of examples 127 and 128 were obtained in the same manner as in example 102.

Example 127

3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]-3-(3-methoxypyridine-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=4.2, and 1.5 Hz), 7,58-7,30 (5H, m)6,91 (1H, d, J=8,4 Hz), 3,92-are 3.90 (6H, m), a-3.84 (2H, d, J=6.9 Hz), 3,52 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), measuring 2.20 (1H, q, J=6.9 Hz), of 1.06 (6H, d, J=6,9 Hz).

Example 128

3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methoxypyridine-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=4,5, 1.5 Hz), 7,60-7,30 (5H, m), 6.90 to (1H, d, J=8 Hz), 4,90-is 4.85 (1H, m), 3,90-3,88 (6H, m), 3,51 (2H, d, J=6.9 Hz), a 3.01 (2H, t, J=6.9 Hz), 2.00 in is 1.81 (6H, m), 1,64-to 1.60 (2H, m).

Example 129

Using 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-3-(3-methoxypyridine-2-yl)propane-1-she obtained in example 125, 44 mg of a white powder of 1-(3-methoxypyridine-2-yl)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propane-1-she's got in the same way as in example 111.

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=4.2, and 1.2 Hz), of 7.70 (1H, DD, J=8,4, 1.8 Hz), 7,60 (1H, d, J=1,8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,47-to 7.32 (2H, m), of 6.96 (1H, d, J=8,4 Hz), of 4.45 (2H, q, J=8,4 Hz), 3.95 to 3,88 (6H, m), 3,52 (2H,, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz).

Example 130

2 g of methyl 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]propionate obtained in reference example 48, and 1 g of methyl 3-ethoxypyridine was dissolved in 10 ml of dimethylformamide while stirring, to the mixture was added a solution of 1.81 g of tert-pentoxide, sodium under ice cooling and stirred for 30 minutes. The mixture was again stirred for 4 hours at room temperature and the reaction mixture was added ice followed by the addition of saturated aqueous solution of ammonium chloride for further mixing. After stirring the reaction mixture for 30 minutes, to the mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated under reduced pressure. The obtained residue eyes is Ali column chromatography on silica gel (n-hexane:ethyl acetate = 1:1) to obtain, thus, 1.5 g of a colorless oily substance methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(3-ethoxypyridine-2-yl)-3-oxopropionate.

1H-NMR (CDCl3) δ: by 8.22 (1H, DD, J=4.2, and 1.2 Hz), EUR 7.57-7,27 (10H, m)6,91 (1H, d, J=9.0 Hz), 5,18-5,12 (3H, m), of 4.12 (2H, q, J=6.9 Hz), to 3.92 (3H, s), the 3.65 (3H, s), 3,30 is 3.23 (2H, m)of 1.46 (3H, t, J=6.9 Hz).

Example 131

Using 1.5 g of methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(3-ethoxypyridine-2-yl)-3-oxopropionate obtained in example 130, 0.7 g of pale yellow oily substance, 1-(3-ethoxypyridine-2-yl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she's got in the same way as in example 125.

1H-NMR (CDCl3) δ: 8,23 (1H, DD, J=4.2, and 1.2 Hz), 7,55-7,49 (2H, m), 7,45 (1H, s), 7,42-7,28 (2H, m), to 6.88 (1H, d, J=8.7 Hz), 5,70 (1H, s), 4,11 (2H, q, J=6.9 Hz), 3,49 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=6.9 Hz), of 1.46 (3H, t, J=6.9 Hz).

Example 132

Using 0.2 g of 1-(3-ethoxypyridine-2-yl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she obtained in example 131, 0.2 g of pale yellow oily substance, 3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-ethoxypyridine-2-yl)propane-1-he was received in the same manner as in example 102.

1H-NMR (CDCl3) δ: 8,23 (1H, DD, J=4,5, 1.5 Hz), EUR 7.57 was 7.45 (2H, m), 7,44 (1H, d, J=0.9 Hz), 7,38-7,28 (2H, m), 6.89 in (1H, d, J=8.7 Hz), 4,89-to 4.87 (1H, m), of 4.12 (2H, q, J=6.9 Hz), 3,94-3,91 (5H, m), 3,88 (3H, s)to 3.49 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), 2,01-of 1.81 (6H, m), 1,65 is 1.58 (2H, m)of 1.47 (3H, t, J=6.9 Hz).

Using 1-(3-toxified the h-2-yl)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-it, obtained in example 131, the compounds of examples 133 and 134 received in the same manner as in example 102.

Example 133

3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-ethoxypyridine-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,23 (1H, DD, J=4.2, and 1.5 Hz), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), to 7.50 (1H, d, J=1,8 Hz), was 7.45 (1H, d, J=1,8 Hz), 7,38-7,28 (2H, m)6,91 (1H, d, J=8,4 Hz), of 4.12 (2H, q, J=6.9 Hz), 3,94-3,91 (5H, m), 3,49 (2H,, t, J=7.2 Hz), to 3.02 (2H, t, J=7.2 Hz), of 1.46 (3H, t, J=6.9 Hz), 1,42-1,32 (1H, m), 0,69-of 0.62 (2H, m), and 0.40 and 0.35 (2H, m).

Example 134

1-(3-ethoxypyridine-2-yl)-3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-he

1H-NMR (CDCl3) δ: 8,23 (1H, DD, J=4,5, 1.5 Hz), 7,56 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,45 (1H, s), 7,38-7,28 (2H, m), 6.90 to (1H, d, J=8,4 Hz), of 4.12 (2H, q, J=6.9 Hz), 3,90 (3H, s), 3,85 (2H, d, J=6,6 Hz), a 3.50 (2H, t, J=6.9 Hz), to 3.02 (2H, t, J=6.9 Hz), 2,19 (2H, cut, J=6,6 Hz)of 1.47 (3H, t, J=6.9 Hz), of 1.05 (6H, d, J=6,6 Hz).

Example 135

5 g of methyl 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]propionate obtained in reference example 48, and 3.2 g of methyl 3-methylpyridine was dissolved in 150 ml of dimethoxyethane. While stirring the solution under ice cooling to the mixture was added 1.2 g of sodium hydride and continued stirring. The reaction mixture was heated and boiled under reflux for 4 hours. Upon completion of the reaction, to the mixture was added saturated aqueous solution of ammonium chloride while stirring under cooling with ice and continued mixing of the sm is si. After stirring the reaction mixture for 30 minutes, to the mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1) obtaining, thus, 5.5 g of colorless oily substance methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(3-methylpyridin-2-yl)-3-oxopropionate.

1H-NMR (CDCl3) δ: 8,49 (1H, DD, J=4,8, 1.2 Hz), to 7.59-7,28 (10H, m)6,91 (1H, d, J=9.0 Hz), 5,23-5,16 (3H, m), 3,91 (3H, s), the 3.65 (3H, s), 3,37-3,18 (2H, m) at 2.59 (3H, s).

Example 136

5.5 g of methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(3-methylpyridin-2-yl)-3-oxopropionate obtained in example 135 was dissolved in 20 ml of ethanol, to the mixture was added 80 ml of 5N. an aqueous solution of hydrochloric acid and the mixture was stirred under heating at 80°C for 1.5 hours. While stirring and cooling with ice, the reaction mixture was neutralized using 5N. an aqueous solution of sodium hydroxide and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained crude crystals was recrystallized using a mixture of 20 ml ethanol and 40 ml of n-hexane to obtain, thus, 1.92 g of pale yellow is th powdery 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,49 (1H, DD, J=4,5, 1.2 Hz), 7,60-7,51 (3H, m), 7,44 (1H, d, J=0.9 Hz), 7,41-7,29 (1H, m), 6.89 in (1H, DD, J=7,8, 1.2 Hz), of 5.68 (1H, s), 3,93 (3H, s)to 3.58 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), 2.57 m (3H, s).

Example 137

0.3 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, and 0.4 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 5 ml of ethanol to the mixture was added 0.24 g (methyl bromide)cyclopropane and the mixture was heated and boiled under reflux for 4.5 hours. The mixture was left to cool and then to the reaction mixture was added water and was carried out by extraction with ethyl acetate. The extract is washed twice with water, the organic layer was then concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1) obtaining, thus, 0.2 g of white powdery 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), 7,60-rate of 7.54 (2H, m), 7,49 (1H, d, J=1,8 Hz), 7,45 (1H, s), 7,34-7,29 (1H, m)6,91 (1H, d, J=8.7 Hz), 3,94-3,91 (5H, m), of 3.60 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), 2.57 m (3H, s), 1,40-1,32 (1H, m), 0,69-of 0.62 (2H, m), 0,41-0,35 (2H, m).

Example 138

to 0.23 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, and 0.3 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 5 ml of ethanol to the mixture was added 0.21 g e is elided and the mixture was heated and boiled under reflux for 4 hours. The mixture was left to cool and then to the reaction mixture was added water and was carried out by extraction with ethyl acetate. The extract is washed twice with water, the organic layer was then concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1) obtaining, thus, 0.17 g of white powdery 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,24 (1H, d, J=4, 2 Hz), 7,58-of 7.55 (2H, m), 7,51 (1H, d, J=2.1 Hz), 7,45 (1H, s), make 6.90 (1H, d, J=8,4 Hz), 4,19 (2H, q, J=7.2 Hz), 3,91 (3H, s)and 3.59 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2.57 m (3H, s), for 1.49 (3H, t, J=7.2 Hz).

Example 139

0.3 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, and 0.4 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 5 ml of ethanol to the mixture was added to 0.23 g of 2-bromopropane and the mixture was heated and boiled under reflux for 4.5 hours. The mixture was left to cool, then to the reaction mixture was added water and was carried out by extraction with ethyl acetate. The extract is washed twice with water, the organic layer was then concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1) obtaining, thus, 0.16 g of white powdery 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol--yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.59-7,53 (3H, m), 7,45 (1H, s), 7,34-7,31 (1H, m)6,91 (1H, d, J=8.7 Hz)and 4.65 (1H, Sept., J=6.0 Hz), with 3.89 (3H, s)and 3.59 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), 2,62 (3H, s)of 1.39 (6H, d, J=6.0 Hz).

Example 140

0.3 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, and 0.3 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 6 ml of ethanol, to the mixture was added to 0.22 g allylbromide and the mixture was heated and boiled under reflux for 4 hours. The mixture was left to cool and then to the reaction mixture was added water and was carried out by extraction with ethyl acetate. The extract is washed twice with water, the organic layer was then concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1) obtaining, thus, 0.18 g of white powdery 3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,51-8,48 (1H, m), 7,60-7,56 (2H, m), 7,52 (1H, d, J=2.1 Hz), 7,45 (1H, s), 7,34-7,29 (1H, m), 6,92 (1H, d, J=8.7 Hz), 6,16-6,05 (1H, m), 5,48 is 5.28 (2H, m), 4,69-of 4.66 (2H, m)to 3.92 (3H, s), of 3.60 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), to 2.57 (3H, s).

Example 141

0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, and 0.15 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 5 ml of ethanol to the mixture was added to 0.13 g (methyl bromide)cyclob the Tana and the mixture was heated and boiled under reflux during the night. The mixture was left to cool and then to the reaction mixture was added water and was carried out by extraction with ethyl acetate. The extract is washed twice with water, the organic layer was then concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 2:1) obtaining, thus, 90 mg of white powdery 3-[2-(3-cyclobutylmethyl-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), 7,60-7,51 (3H, m), 7,45 (1H, d, J=2.1 Hz), 7,34-7,29 (1H, m), 6.89 in (1H, d, J=8.7 Hz), 4,07 (2H, d, J=6.9 Hz), with 3.89 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz,), 2,89-and 2.83 (1H, m), to 2.57 (3H, s), 2,22 and 2.13 (2H, m), 2.00 in of 1.84 (4H, m).

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he obtained in example 136, the compounds of examples 142-154 was obtained in the same manner as in example 137.

Example 142

3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), 7,60-7,53 (2H, m)to 7.50 (1H, d, J=1,8 Hz), 7,45 (1H, s), 7,34-7,28 (1H, m), 6.90 to (1H, d, J=8,4 Hz), 3,90 (3H, s), a-3.84 (2H, d, J=6.9 Hz), of 3.60 (2H, t, J=7.8 Hz), 3,01 (2H,, t, J=7.8 Hz), to 2.57 (3H, s), measuring 2.20 (1H, cut, J=6,9 Hz)of 1.05 (6H, d, J=6,9 Hz).

Example 143

3-[2-(4-methoxy-3-propoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.59-rate of 7.54 (2H, m), 7,51 (1H, d, J=1,8 Hz), to 7.50 (1H, s), 7,34-7,29 (1H, m), 6.90 to (1H, d, J=8,4 Hz), of 4.05 (2H, t, J=6.9 Hz), 3,91 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s), 1,90 (2H, cut, J=6,9 Hz)of 1.24 (3H, t, J=6.9 Hz).

Example 144

3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.59-to 7.50 (3H, m), 7,44 (1H, d, J=1.2 Hz), 7,34-7,31 (1H, m), 6.89 in (1H, d, J=8,4 Hz), 4,90-4,84 (1H, m), 3,88 (3H, s)and 3.59 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2.57 m (3H, s), 2,03 and 1.80 (6H, m), 1,64 is 1.58 (2H, m).

Example 145

3-[2-(4-methoxy-3-(2-propenyloxy)phenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), to 7.67-7,63 (2H, m), 7,58 (1H, d, J=8.1 Hz), 7,46 (1H, s), 7,34-7,30 (1H, m), 6,93 (1H, DD, J=6,6, 2.4 Hz), 4,82 (2H, d, J=2.4 Hz), to 3.92 (3H, s), of 3.60 (2H, t, J=7.2 Hz), 3,01 (2H,, t, J=7.2 Hz), 2,58 (3H, s), 2,53 (1H, t, J=2,4 Hz).

Example 146

3-[2-(3-(3-butenyloxy)-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4.2, and 1.5 Hz), to 7.59-of 7.55 (2H, m), 7,52 (1H, d, J=2.1 Hz), was 7.45 (1H, d, J=2.1 Hz), 7,34-7,29 (1H, m), 5,97-to 5.85 (1H, m), 5,23-5,09 (2H, m), 4,14 (2H, t, J=6.9 Hz), 3,91 (3H, s), of 3.60 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), 2,68-2.57 m) (5H, m).

Example 147

3-[2-(3-butoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4,8 Hz), to 7.59-7,51 (3H, m), 7,45 (1H, s), 7,34-7,30 (1H, m), 6.90 to (1H, d, J=8.7 Hz), 4.09 to (2H, t, J=6.6 Hz), 3,90 (3H, s), of 3.60 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), to 2.57 (3H, ), to 1.86 (2H, TD, J=7,2, and 6.6 Hz), 1.56 to to 1.45 (2H, m), 0,99 (3H, t, J=7.2 Hz).

Example 148

3-[2-(3-cyclohexylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), to 7.61-7,53 (2H, m), 7,49 (1H, d, J=1,8 Hz), 7,45 (1H, s), 7,34-7,28 (1H, m), 6.89 in (1H, d, J=8.7 Hz), 3,90-3,86 (5H, m), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H with), 1,94-of 1.85 (3H, m), 1,79-of 1.57 (3H, m), 1,38-0,88 (5H, m).

Example 149

3-[2-(4-methoxy-3-(4-pentyloxy)phenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.59-rate of 7.54 (2H, m), 7,51 (1H, d, J=2.1 Hz), 7,45 (1H, s), 7,34-7,29 (1H, m)6,91 (1H, d, J=8,4 Hz), 5,91-5,80 (1H, m), 5,11-equal to 4.97 (2H, m), 4,10 (2H, d, J=6.6 Hz), 3,91 (3H, C)of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s), 2,30-2,22 (2H, m), 2.05 is-of 1.92 (2H, m).

Example 150

3-[2-(4-methoxy-3-penetrometer)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,48 (1H, DD, J=4,5, and 0.9 Hz), 7,60-7,49 (3H, m), the 7.43 (1H, s), 7,35-7,20 (6H, m)6,91 (1H, d, J=8.7 Hz), 4,27 (2H, t, J=7.5 Hz), 3,91 (3H, s)to 3.58 (2H, t, J=7.2 Hz), 3,19 (2H, t, J=7.5 Hz), of 3.00 (2H,, t, J=7.2 Hz), to 2.55 (3H, s).

Example 151

3-{2-[4-methoxy-3-(3-phenylpropoxy)phenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), 7,58 (1H, d, J=2.1 Hz), 7,55 (1H, d, J=2.1 Hz), 7,49 (1H, d, J=2.1 Hz), 7,44 (1H, s), 7,34-to 7.15 (6H, m)6,91 (1H, d, J=8,4 Hz), 4,11 (2H, t, J=6.6 Hz), to 3.92 (3H, s), of 3.60 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), 2,84 (2H, t, J=7.5 Hz), to 2.57 (3H, s), measuring 2.20 (2H, TT, J=7,5, and 6.6 Hz).

Example 152

Using 0.5 g cyclopentadienylmanganese obtained in reference example 52, and 0.2 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, 90 mg of a white poroshkoobraz the th 3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-he received in the same way, as in example 137.

1H-NMR (CDCl3) δ: 8,49 (1H, d, J=3,9 Hz), to 7.59-to 7.50 (3H, m), 7,45 (1H, s), 7,34-7,29 (1H, m), 6.90 to (1H, d, J=8,4 Hz), 3,95 (2H, d, J=7,2 Hz), 3,90 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, ), 2,54-to 2.41 (1H, m), 1.91 a-1,82 (2H, m), 1,68-of 1.56 (4H, m), 1,42-1,24 (2H, m).

Example 153

Using 0.16 g of 2-cyclopropylacetylene obtained in reference example 50, and 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, 0.1 g of white powdery 3-{2-[3-(2-cyclopropylmethoxy)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-it was received in the same manner as in example 137.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.5 Hz), 7,60-rate of 7.54 (3H, m), 7,46 (1H, s), 7,35-7,27 (1H, m)6,91 (1H, d, J=8.1 Hz), 4,18 (2H, t, J=6.9 Hz), 3,91 (3H, s), 3,61 (2H, t, J=7.5 Hz), to 3.02 (2H, t, J=7.5 Hz), 2,58 (3H, (C), of 1.78 (2H, q, J=6.9 Hz), 0,91-0,80 (1H, m), 0,53-0,46 (2H, m), 0,16-0,11 (2H, m).

Example 154

Using 0,19 g 2-cyclopentylpropionate obtained in reference example 51, and 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, of 0.13 g of white powdery 3-{2-[3-(2-cyclopentyloxy)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-it was received in the same manner as in example 137.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), 7,60 is 7.50 (3H, m), 7,45 (1H, s), 7,34-7,30 (1H, m), 6.90 to (1H, d, J=8,4 Hz), 4,10 (2H, t, J=6.9 Hz), to 3.92 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H with), 2,01-to 1.79 (5H, what), 1,67 of 1.50 (5H, m), 1,24-1,12 (2H, m).

Example 155

to 0.23 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, and 0.28 g of potassium carbonate was dissolved in 5 ml of dimethylformamide. To the mixture was added 0.29 grams 1,1,1-Cryptor-2-iodata and the mixture was stirred under heating at 80°C during the night. The reaction mixture was allowed to cool, then to the mixture was added water and was carried out by extraction with ethyl acetate. The mixture was twice washed with water and then the organic layer was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (dichloromethane:ethyl acetate = 1:1) to obtain 0.14 g of white powdery 3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, and 0.9 Hz), of 7.70 (1H, DD, J=8,4, and 2.1 Hz), 7,60-7,56 (2H, m), 7,46 (1H, d, J=2.1 Hz), 7,35-7,30 (1H, m), of 6.96 (1H, d, J=8,4 Hz), of 4.45 (2H, q, J=8,4 Hz)to 3.92 (3H, s), of 3.60 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), to 2.57 (3H, s).

Example 156

Using 0.1 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, 45 mg of pale yellow powder of 3-{2-[4-methoxy-3-(3-methyl-2-butenyloxy)phenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-she's got such the same way as in example 155.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.59-7,52 (3H, m), 7,45 (1H, s), 7,34-7,29 (1H, m), 6.90 to (1H, d, J=8,4 Hz), 5,8-5,52 (1H, m), with 4.64 (2H, d, J=6.9 Hz), 3,91 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s)of 1.78 (3H, d, J=0.9 Hz), 1.77 in (3H, s).

Example 157

Using 0.6 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, 0.31 g of white powdery 3-{2-[3-(2-cyclohexyloxy)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-he was received in the same manner as in example 155.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), 7,60-7,56 (3H, m), 7,45 (1H, s), 7,34-7,29 (1H, m)6,91 (1H, d, J=9.0 Hz), 5,99-5,88 (2H, m), 4,88 (1H, users), the 3.89 (3H, s), of 3.60 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7,2 Hz), to 2.57 (3H, s), 2,17-of 1.84 (5H, m), 1,71-to 1.61 (1H, m).

Example 158

0.3 g of 3-{2-[3-(2-cyclohexyloxy)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 157, was dissolved in 20 ml of ethanol. To the mixture was added 50 mg of 10% palladium-on-carbon in powder form and the mixture was stirred at room temperature for 2 hours. The catalyst was removed via filtration and the filtrate was then concentrated. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain 0.2 g of pale yellow oily 3-[2-(3-cyclohexyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), to 7.59-rate of 7.54 (3H, m), 7,45 (1H, s), 7,34-7,30 (1H, m)6,91 (1H, d, J=8.1 Hz), 4,35-of 4.25 (1H, m)to 3.89 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s), 2,07-2,02 (2H, m), of 1.84 and 1.80 (2H, m), 1,60-is 1.51 (4H, m), 1,43 is 1.23 (2H, m).

Example 159

0.26 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 136, was dissolved in 10 ml of tetrahydrofuran. To the resulting solution were added 0.2 g of 2-hydroxyindole, 0.75 ml of diisopropylcarbodiimide (40%solution in toluene) and 0.31 g three(n-butyl)phosphine, and the mixture was stirred at 50°C. After 3 hours the mixture was again added 0.2 g of 2-hydroxyindole, 0.75 ml of diisopropylcarbodiimide (40%solution in toluene) and 0.31 g three(n-butyl)phosphine, and the mixture was stirred at 50°C during the night. The reaction mixture was concentrated under reduced pressure. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate:dichloromethane = 1:1:1) and recrystallized from a mixture of acetone/diisopropyl ether to obtain of 0.13 g of colorless powdery 3-{2-[3-(indan-2-yloxy)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,51 (1H, userd, J=4,8 Hz), 7,62-7,16 (9H, m)6,91 (1H, d, J=8.7 Hz), from 5.29 (1H, TT, J=6,6, 3,9 Hz), 3,85 (3H, s), 3,63 (2H, t, J=7.2 Hz), of 3.45 (2H, DD, J=16,8, and 6.6 Hz), 3,26 (2H, DD, J=16,8, 3,9 Hz), 3,01 (2H,, t, J=7.2 Hz), 2,58 (3H, s).

Example 160

2 g of methyl 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]propionate obtained in reference example 48, and 1.5 g of methylpyridine was dissolved in 40 ml of dimethoxyethane. To the mixture was added 0.33 g of sodium hydride under ice cooling and paramasivan the and and the stirring continued. The reaction mixture was heated and boiled under reflux for 2 hours. Upon completion of the reaction, to the mixture was added saturated aqueous solution of ammonium chloride under ice cooling and stirring and the mixture was stirred. The reaction mixture was stirred for 30 minutes, then to the mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated by removing the solvent under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain 2 g of colorless, oily methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-oxo-3-pyridin-2-ylpropionic.

1H-NMR (CDCl3) δ: 8,67 (1H, DD, J=4.2, and 0.9 Hz), 8,07 (1H, DD, J=7,8, and 2.1 Hz), 7,83 (1H, TD, J=7,8, 1.8 Hz), 7,55-7,30 (9H, m), 6.90 to (1H, d, J=9.0 Hz), from 5.29 (1H, t, J=7.8 Hz), 5,16 (2H, s), 3,91 (3H, s), 3,66 (3H, s), 3,36 of 3.28 (2H, m).

Example 161

Using 2 g of methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-oxo-3-(pyridin-2-yl)propionate obtained in example 160, of 0.48 g of white powdery 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(pyridine-2-yl)propane-1-she's got in the same way as in example 136.

1H-NMR (CDCl3) δ: 8,67 (1H, DD, J=4.2, and 0.9 Hz), with 8.05 (1H, DD, J=7,8, and 2.1 Hz), 7,83 (1H, TD, J=7,8, 1.8 Hz), 7,55-the 7.43 (4H, m), to 6.88 (1H, DD, J=7,8, and 2.1 Hz), 5,72 (1H, s), 3,93 (3H, s)to 3.64 (2H, t, J=7.5 Hz), 3,03 (2H, t, J=7.5 Hz).

Example 162

0.15 g 3[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(pyridine-2-yl)propane-1-it, obtained in example 161, and 0.2 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 5 ml of ethanol. To the mixture was added 0.14 g (methyl bromide)CYCLOBUTANE and the mixture was heated and boiled under reflux during the night. The reaction mixture was allowed to cool, then to the mixture was added water and was carried out by extraction with ethyl acetate. The mixture was twice washed with water and then the organic layer was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel (dichloromethane:ethyl acetate = 5:1) to obtain 50 mg of white powdery 3-[2-(3-cyclobutylmethyl-4-methoxyphenyl)oxazol-4-yl]-1-(pyridine-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,68 (1H, d, J=4.5 Hz), with 8.05 (1H, d, J=7.8 Hz), 7,83 (1H, TD, J=7,8, 1.8 Hz), 7,58-7,44 (4H, m), 6.90 to (1H, d, J=8,4 Hz), 4,07 (2H, d, J=6.9 Hz), with 3.89 (3H, s), the 3.65 (2H, t, J=7.5 Hz), 3,05 (2H, t, J=7.5 Hz), 2,94-of 2.81 (1H, m), 2,24-2,04 (2H, m), 2.00 in is 1.81 (4H, m).

Example 163

Using 0.3 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(pyridine-2-yl)propane-1-she obtained in example 161, 0.28 g of white powdery 3-[2-(4-methoxy-3-(4-pentyloxy)phenyl)oxazol-4-yl]-1-(pyridine-2-yl)propane-1-she's got in the same way as in example 102.

1H-NMR (CDCl3) δ: 8,69 (1H, DD, J=4.2, and 1.5 Hz), with 8.05 (1H, d, J=7.8 Hz), the 7.85 (1H, t, J=7.8 Hz), 7,60-7,46 (4H, m)6,91 (1H, d, J=8,4 Hz), of 5.92-of 5.83 (1H, m), 5,11-4,99 (2H, m), 4,11 (2H, d, J=6.9 Hz), 3,91 (3H, s), 3,65 (2H, t, J=7.5 Hz), 3,05 (2H, t, J=7.5 Hz), 2,28-of 2.23 (2H, m)to 1.98 (2H, t, J=7.5 Hz).

Example 164

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), 7,62-7,58 (2H, m), 7,49-7,30 (7H, m), 7,02-6,91 (3H, m), 6,12-of 6.02 (1H, m), 5,42 (1H, DD, J=17.4 years, 1.5 Hz), and 5.30 (1H, DD, J=a 10.5, 1.5 Hz), 5,19 (2H, s), 4,65-to 4.62 (2H, m)to 3.92 (3H, (C), of 3.42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz).

Example 165

Using 1.4 g of 1-(2-allyloxyphenyl)-3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she obtained in example 164, 0.55 g of pale yellow oily 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-hydroxyphenyl)p is opan-1-she's got in the same way, as in example 101.

1H-NMR (CDCl3) δ: 12,5 (1H, s), 7,81 (1H, DD, J=7,8, 1.5 Hz), EUR 7.57-7,30 (4H, m), 6,98 (1H, d, J=8.1 Hz), 6,92-6,86 (2H, m), 5,73 (1H, users), of 3.94 (3H, s), 3,44 (2H, t, J=7.5 Hz), to 3.02 (2H, t, J=7.5 Hz).

Example 166

Using 0.5 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-hydroxyphenyl)propane-1-she obtained in example 165, and 0.61 g of white powdery 3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-allyloxyphenyl)propane-1-she's got in the same way as in example 111.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, and 2.1 Hz), 7,58 (1H, DD, J=8,1, 2,1 Hz), 7,52 (1H, d, J=2.1 Hz), 7,45-7,40 (2H, m), 7,02-of 6.90 (3H, m), 6,16-6,03 (2H, m), 5,47 at 5.27 (4H, m), 4,68-to 4.62 (4H, m)to 3.92 (3H, s), 3,42 (2H, t, J=6,9 Hz)to 2.99 (2H, t, J=6.9 Hz).

Example 167

Using 1.1 g of methyl 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]propionate obtained in reference example 48, 1 g of a yellow oily methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(2-methoxyphenyl)-3-oxopropionate was obtained in the same manner as in example 100.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57-7,53 (3H, m), of 7.48-7,30 (6H, m), 6,97 (1H, t, J=7.2 Hz), 6,91 (2H, d, J=7,8 Hz)to 5.17 (2H, s), 4,99 (1H, t, J=6.9 Hz), to 3.92 (3H, s), 3,90 (3H, s), of 3.69 (3H, s), 3.27 to-3,19 (2H, m).

Example 168

Using 1 g of methyl 2-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-3-(2-methoxyphenyl)-3-oxopropionate obtained in example 167, 0,63 g of white powdery 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-she's got t is Kim the same way, as in example 101.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=8,4, and 2.1 Hz), 7,56-7,52 (2H, m), 7,44-7,41 (2H, m), 6,99-6,87 (3H, m), of 3.95 (3H, s)to 3.89 (3H, s)to 3.38 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz).

Example 169

Using 0,22 g 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-she obtained in example 168, 90 mg of colorless, oily 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-she's got in the same way as in example 102.

1H-NMR (CDCl3) δ: of 7.70 (1H, d, J=7.5 Hz), EUR 7.57 (1H, d, J=8.1 Hz), 7,54 (1H, s), 7,47-7,40 (2H, m), 7,01-6,89 (3H, m), 4,67-to 4.62 (1H, m), 3,91 (6H, s)to 3.38 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), of 1.39 (6H, d, J=6,3 Hz).

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-he obtained in example 168, the compounds of examples 170-173 was obtained in the same manner as in example 102.

Example 170

3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: 7,69-7,40 (4H, m), 6,99-6,89 (4H, m), 3,94-3,89 (8H, m), 3,37 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), of 1.40 and 1.35 (1H, m), 0.67 and is 0.65 (2H, m), 0,38-0,36 (2H, m).

Example 171

3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,56 (1H, DD, J=8,4, and 2.1 Hz), 7,51 (1H, s), the 7.43 (1H, TD, J=8,4, 1.8 Hz), 6,99-to 6.88 (3H, m), 4,48 (1H, users), the 3.89 (3H, s), 3,88 (3H, s)to 3.38 (2H, t, J=6.6 Hz), 2,98 (2H, t, J=6.6 Hz), 2,04-of 1.85 (4H, m), 1,63-of 1.55 (4H, m).

Example 172

3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl-1-(2-methoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57 (1H, DD, J=8,1, 2,1 Hz), 7,51 (1H, d, J=1,8 Hz), 7,47-7,41 (2H, m), 7,01-6,89 (3H, m), 4,18 (2H, q, J=7.8 Hz), of 3.94 (3H, s), 3,90 (3H, s)to 3.38 (2H, t, J=6.6 Hz), 2,99 (2H, t, J=6.6 Hz), for 1.49 (3H, t, J=7,8 Hz).

Example 173

3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,58 and 7.36 (4H, m), 7,01-6,89 (3H, m), 3,90 (6H, s), a-3.84 (2H, d, J=6.6 Hz), to 3.38 (2H, t, J=6.9 Hz), 2,99 (2H, t, J=6.9 Hz), 2,22-2,10 (1H, m)of 1.05 (6H, d, J=6,6 Hz).

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-he obtained in example 168, the compounds of examples 174-175 was obtained in the same manner as in example 111.

Example 174

3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), to 7.59 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), of 7.48-7,41 (2H, m), 7,02-of 6.90 (3H, m), 6,12-6,07 (1H, m), 5,43 (1H, DD, J=17 and 1.5 Hz), 5,31 (1H, d, J=10 Hz), and 4.68 (2H, d, J=5.4 Hz), to 3.92 (3H, s), 3,90 (3H, s)to 3.38 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz).

Example 175

1-(2-methoxyphenyl)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propane-1-he

1H-NMR (CDCl3) δ: of 7.69 (1H, DD, J=7,5, 1.8 Hz), 7,60 (1H, d, J=1,8 Hz), of 7.48-7,42 (2H, m), 7,02-to 6.95 (3H, m), 4,43 (2H, q, J=8,1 Hz)to 3.92 (3H, s), 3,90 (3H, s)to 3.38 (2H, t, J=6.9 Hz), 2,99 (2H, t, J=6.9 Hz).

Example 176

0.4 g of sodium hydride suspended in 20 ml of tetrahydrofuran, and to the mixture was added sequentially 1.13 g of 1-(2-benzyloxy)ethanone and of 1.46 g of 4-chloromethyl-2-(3-cyclopropylmethyl the XI-4-methoxyphenyl)oxazole, obtained in reference example 11, while cooling with ice. The mixture was stirred for 4 hours under heating and boiling under reflux. To the reaction mixture were added saturated aqueous solution of ammonium chloride under ice cooling. After stirring for 15 minutes, to the mixture was added water and was carried out by extraction with ethyl acetate. Was carried out by drying using anhydrous magnesium sulfate and the solvent was removed. Purification was performed using column with silica gel (n-hexane:ethyl acetate = 4:1) and the compound obtained was dissolved in 12 ml of ethanol. Added 35 mg of 10% palladium-on-carbon in powder form and was carried out by stirring in an atmosphere of hydrogen overnight. The catalyst was removed via filtration and the resulting filtrate was concentrated. The residue was purified using a column with silica gel (n-hexane:ethyl acetate = 4:1) obtaining of 0.43 g of white powdery 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-hydroxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: 12,2 (1H, s), 7,83 (1H, d, J=1.5 Hz), 7,80-7,44 (4H, m), 7,00-6,87 (3H, m), 3,94-to 3.92 (5H, m), 3,44 (2H, t, J=7.2 Hz), 3,03 (2H, t, J=7.2 Hz), 1,37-of 1.26 (1H, m), 0.70 to of 0.65 (2H, m), 0,41 is 0.37 (2H, m).

Example 177

2 g of 4-chloromethyl-2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazole obtained in reference example 11, and 3.6 g of 1-(2-allyloxyphenyl)ethanone obtained in reference example 53, astoral in 40 ml of tetrahydrofuran. To the mixture was added 0.55 g of sodium hydride under ice cooling and stirring and the mixture was stirred. The reaction mixture was heated and boiled under reflux for 6 hours. Upon completion of the reaction was added saturated aqueous solution of ammonium chloride under ice cooling and the mixture was stirred. The reaction mixture was stirred for 30 minutes, then to the mixture was added water and was carried out by extraction with ethyl acetate. The organic layer twice washed with water and concentrated by removing the solvent under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain 0.5 g of powdered 1-(2-allyloxyphenyl)-3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, and 2.1 Hz), 7,49 (1H, d, J=2.1 Hz), 7,45-7,39 (2H, m), 7,02-6,89 (3H, m), 6,09-of 6.02 (1H, m), the 5.45 of 5.26 (2H, m), 4,65-to 4.62 (2H, m), 3,94-3,91 (5H, m), 3,42 (2H,, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), of 1.45 and 1.35 (1H, m), 0,68-of 0.62 (2H, m), 0,40-0,36 (2H, m).

Example 178

Using 1.4 g of 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole obtained in reference example 35, and 0.88 g of 1-(2-allyloxyphenyl)ethanone obtained in reference example 53, of 0.42 g of a white powder of 1-(2-allyloxyphenyl)-3-[2-(3,4-dioxyphenyl)oxazol-4-yl]propane-1-she's got in the same way as in example 177.

1H-NMR (CDCl3) δ: of 7.69 (1H, DD, =7,5, and 2.1 Hz), 7,56-7,51 (2H, m), 7,45-7,39 (2H, m), 7,02-6,89 (3H, m), 6,14-6,01 (1H, m), 5,42 (1H, DD, J=17 and 1.5 Hz), from 5.29 (1H, DD, J=a 10.5, 1.5 Hz), 4,65-to 4.62 (2H, m), 4,20-4,10 (4H, m), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), 1,50 (6H, t, J=7.2 Hz).

Example 179

Using 0.31 g of 1-(2-chlorophenyl)ethanone and 0.59 g of 4-chloromethyl-2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazole obtained in reference example 11, 0.11 g of colorless oily 1-(2-chlorophenyl)-3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she's got in the same way as in example 177.

1H-NMR (CDCl3) δ: 7,60-of 7.55 (2H, m), 7,49-the 7.43 (2H, m), 7,40 (1H, s), 7,39-7,30 (2H, m)6,91 (1H, d, J=8.7 Hz), 3,94-3,91 (5H, m)to 3.36 (2H, t, J=6.9 Hz), a 3.01 (2H, t, J=6.9 Hz), 1,37-of 1.29 (1H, m), is 0.69 to 0.63 (2H, m), 0,40-0,37 (2H, m).

Example 180

Using 2 g of methyl 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]propionate obtained in reference example 54, and 1.3 g of ethyl 3-methylpyridine, 0.8 g of yellow oily methyl 2-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-3-(3-methylpyridin-2-yl)-3-oxopropionate was obtained in the same manner as in example 124,

1H-NMR (CDCl3) δ: 8,50 (1H, m), 7,60-7,40 (4H, m), 7,30 (1H, m), to 6.88 (1H, d, J=8,4 Hz), 5,20 (1H, t, J=7.2 Hz), 4,20-of 4.05 (4H, m), 2,99 (3H, s), 3,35-3,20 (2H, m), 2,59 (3H, s)of 1.47 (3H, t, J=6.9 Hz), of 1.47 (3H, t, J=6,9 Hz).

Example 181

0.8 g of methyl 2-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-3-(3-methylpyridin-2-yl)-3-oxopropionate obtained in example 180 was added to a mixture of 5 ml of acetic acid and 1.5 ml of concentrated hydrochloric acid and the resulting mixture is stirred at 110°C for 4 hours. After cooling the resulting solution to room temperature was slowly added 30 ml of ethyl acetate and 30 ml of saturated sodium hydrogen carbonate solution under stirring and stirring is then continued. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified column chromatography on silica gel (ethyl acetate:n-hexane = 3:1) and then recrystallized from a mixture of ethyl acetate/n-hexane to obtain 0.28 g of white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,49 (1H, m), 7,60 is 7.50 (3H, m), 7,44 (1H, s), 7,32 (1H, m), 6.90 to (1H, d, J=8.1 Hz), 4,17 (2H, q, J=6.9 Hz), of 4.13 (2H, q, J=6.9 Hz), 3,51 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), to 2.57 (3H, s), to 1.48 (3H, t, J=6.9 Hz), of 1.47 (3H, t, J=6.9 Hz).

Example 182

2 g of methyl 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]propionate obtained in reference example 54, and 1.5 g of ethyl 2-ethoxybenzoate was dissolved in 10 ml of dimethylformamide. To the mixture was added 1,81 g of tert-pentoxide, sodium under ice cooling and stirring and the mixture was stirred for 30 minutes. The reaction mixture is again stirred at room temperature for 5 hours and to the mixture was added to ice. To the mixture was added saturated aqueous solution of ammonium chloride and the mixture was stirred. The reaction mixture was stirred for 30 minutes, then to the mixture was added water and implement the Yali extraction with ethyl acetate. The organic layer twice washed with water and concentrated by removing the solvent under reduced pressure. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 1:1). The obtained yellow oily substance was added to a mixture of 5 ml of acetic acid and 1.5 ml of concentrated hydrochloric acid and the resulting mixture was stirred at 110°C for 4 hours. After cooling the mixture to room temperature was slowly added 30 ml of ethyl acetate and 30 ml of saturated sodium hydrogen carbonate solution under stirring and the stirring was continued further. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified column chromatography on silica gel (ethyl acetate:n-hexane = 3:1) and the crude crystals are recrystallized from a mixture of ethyl acetate/n-hexane to obtain and 0.46 g of white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, and 2.1 Hz), 7,60 is 7.50 (2H, m), 7,45-to 7.35 (2H, m), 7,00-to 6.80 (2H, m)to 4.17 (2H, q, J=7.2 Hz), of 4.13 (2H, q, J=7.2 Hz), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=7,2 Hz), to 1.48 (3H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Using methyl 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]propionate obtained in reference example 54, the compounds of examples 183-185 was obtained in the same way, CA is in example 182.

Example 183

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(3-ethoxypyridine-2-yl)propane-1-he

1H-NMR (CDCl3) δ: 8,23 (1H, DD, J=4,5, 1.2 Hz), 7,55 is 7.50 (2H, m), 7,40-of 7.25 (2H, m), 7,45 (1H, s), make 6.90 (1H, d, J=8.1 Hz), 4,20-of 4.05 (6H, m), 3,49 (2H, t, J=7.2 Hz), to 3.02 (2H, t, J=7.2 Hz), of 1.47 (3H, t, J=7.2 Hz), 1,47 (3H, t, J=7.2 Hz), of 1.46 (3H, t, J=7.2 Hz).

Example 184

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(3-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: 8,00-of 7.95 (2H, m), 7,60 is 7.50 (2H, m), the 7.43 (1H, s), 6,95-6,85 (3H, m)to 4.17 (2H, q, J=7.2 Hz), 4,17 (2H, q, J=7.2 Hz), 4.09 to (2H, q, J=7.2 Hz), to 3.34 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz), the 1.44 (3H, t, J=7.2 Hz).

Example 185

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(4-ethoxyphenyl)propane-1-he

1H-NMR (CDCl3) δ: 7,60 is 7.50 (4H, m), 7,44 (1H, s), 7,35 (1H, t, J=7.8 Hz), to 7.09 (1H, DD, J=9,0, 2.4 Hz), 6,10 (1H, d, J=5.4 Hz), of 4.16 (2H, q, J=7.2 Hz), is 4.15 (2H, q, J=7.2 Hz), 4,08 (2H, q, J=7.2 Hz), to 3.38 (2H, t, J=7,2 Hz), to 3.02 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz), of 1.40 (3H, t, J=7.2 Hz).

Example 186

Using 2 g of dimethyl 2-[2-(3,4-bis(benzyloxy)phenyl)oxazol-4-ylmethyl]malonate obtained in reference example 56, 2.2 g of pale yellow oily methyl 2-[2-(3,4-bis-benzyloxyphenyl)oxazol-4-ylmethyl]-3-(3-methylpyridin-2-yl)-3-oxopropionate was obtained in the same manner as in example 100.

1H-NMR (CDCl3) δ: 8,49 (1H, DD, J=4,5, 1.2 Hz), to 7.59-7,28 (15H, m)6,94 (1H, d, J=8,4 Hz), 5,23-5,17 (5H, m), of 3.69 (3H, s), 3,32 is 3.23 (2H, m), 2,59 (3H, s).

Example 187

Using 2.2 g of methyl 2-[2-(3,4-bis-benzyloxyphenyl)oxazol-4-yl is ethyl]-3-(3-methylpyridin-2-yl)-3-oxopropionate, obtained in example 186, 0.24 g of white powdery 3-[2-(3,4-dihydroxyphenyl)oxazol-4-ylmethyl]-1-(3-methylpyridin-2-yl)propane-1-she's got in the same way as in example 136.

1H-NMR (CDCl3) δ: 9,46 (1H, users), to 9.32 (1H, users), 8,54 (1H, d, J=3.0 Hz), 7,80-7,76 (2H, m), 7,54-7,49 (1H, m), 7,32 (1H, d, J=2.1 Hz), 7.23 percent (1H, DD, J=8,4, and 2.1 Hz), PC 6.82 (1H, d, J=8,4 Hz), 3,47 (2H, t, J=7.5 Hz), and 2.83 (2H,, t, J=7.5 Hz), of 2.51 (3H, s).

Example 188

Using 0.12 g of 3-[2-(3,4-dihydroxyphenyl)oxazol-4-ylmethyl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 187, 35 mg of white powdery 3-{2-[3,4-bis-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-she's got in the same way as in example 111.

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), to 7.68 (1H, DD, J=8,4, 1.8 Hz), 7,63 (1H, d, J=1,8 Hz), 7,58 (1H, d, J=8,4 Hz), 7,49 (1H, s), 7,35-7,28 (1H, m),? 7.04 baby mortality (1H, d, J=8,4 Hz), 4,50-4,39 (4H, m), of 3.60 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), at 2.59 (3H, s).

Example 189

Using 0,76 g of 4-chloromethyl-2-(3-ethoxy-4-methoxyphenyl)oxazole obtained in reference example 58, and 0.5 g of 1-(2-allyloxyphenyl)ethanone obtained in reference example 53, of 0.13 g of a white powder of 1-(2-allyloxyphenyl)-3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she's got in the same way as in example 177.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, and 2.1 Hz), 7,56 (1H, DD, J=8,4, and 2.1 Hz), 7,51 (1H, d, J=2.1 Hz), 7,45-7,40 (2H, m), 7,02-6,89 (3H, m), 6,12-6,01 (1H, m), 5,42 (1H, DD, J=17 and 1.5 Hz), 5,28 (1H, DD, J=17 and 1.5 Hz), 4,65-to 4.62 (2H, m), 4,18 (2H, q, J=6,9 is C), to 3.92 (3H, s), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), for 1.49 (3H, t, J=6.9 Hz).

Example 190

2 g of 4-chloromethyl-2-(4-benzyloxy-3-ethoxyphenyl)oxazole obtained in reference example 63, and 0.96 g of 1-(2-ethoxyphenyl)ethanone was dissolved in 20 ml of tetrahydrofuran, and to the mixture was added to 0.47 g of sodium hydride. After foaming, the reaction mixture was heated and boiled under reflux for 3 hours. After cooling, the reaction mixture was added to ice water and was carried out by extraction with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain 0.4 g of colorless powdery 3-[2-(4-benzyloxy-3-ethoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,55-7,30 (8H, m), 6,97 (2H, t, J=7.5 Hz), 6,93 (1H, d, J=7.5 Hz), 5,19 (2H, s), 4,18 (2H, q, J=6.9 Hz), of 4.13 (2H, q, J=6.9 Hz), to 3.41 (2H, t, J=6.9 Hz), 2,99 (2H, t, J=6,9 Hz)to 1.48 (3H, t, J=6.9 Hz), of 1.47 (3H, t, J=6.9 Hz).

Example 191

Using 3-[2-(4-benzyloxy-3-ethoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he obtained in example 190, colorless, oily 3-[2-(3-ethoxy-4-hydroxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he was received in the same manner as in example 2.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,52 (1H, DD, J=8,1, 2,1 Hz), 7,49 (1H, d, J=2.1 Hz), 7,45-7,38 (2H, m), 97 (1H, t, J=7.5 Hz), to 6.95 (1H, d, J=7.5 Hz), 6,93 (1H, d, J=8.1 Hz), of 5.89 (1H, s), 4,20 (2H, q, J=7.2 Hz), of 4.13 (2H, q, J=7.2 Hz), to 3.41 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), of 1.47 (3H, t, J=7.2 Hz), 1,47 (3H, t, J=7.2 Hz).

Example 192

Using 3-[2-(3-ethoxy-4-hydroxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he obtained in example 191, 3-[2-(3-ethoxy-4-isopropoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it is in the form of colorless needle-like crystals were obtained in the same manner as in example 111.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,54-7,51 (2H, m), 7,45-7,39 (2H, m), 6,97 (2H, ushort, J=7.5 Hz), 6,93 (1H, d, J=7.5 Hz), 4,55 (1H, Sept., J=6.0 Hz), 4,14 (2H, q, J=6.9 Hz), of 4.13 (2H, q, J=6.9 Hz), 3,42 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), of 1.47 (3H, t, J=6.9 Hz), a 1.45 (3H, t, J=6.9 Hz), of 1.37 (6H, d, J=6.0 Hz).

Example 193

2,98 g of 2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-carbaldehyde obtained in reference example 64 and 1,72 g of 1-(2-propoxyphenyl)ethanone was dissolved in 50 ml of pyridine. To the mixture was added 2.66 g of potassium carbonate and the mixture was heated and stirred at 120°C for 22 hours. After cooling, the reaction mixture was added to saturated salt solution and was carried out by extraction with ethyl acetate. The organic layer was washed with water and then dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain 1,82 g of colorless oily (E)-3-[2-(3-benzyloxy-4-methox is phenyl)oxazol-4-yl]-1-(2-propoxyphenyl)-2-propen-1-it.

1H-NMR (CDCl3) δ: 7,80 (1H, s), 7,79 (1H, d, J=15.3 Hz), 7,69-7,66 (3H, m), 7,51-to 7.32 (7H, m),? 7.04 baby mortality-to 6.95 (3H, m), a total of 5.21 (2H, s), of 4.05 (2H, t, J=6.3 Hz), of 3.94 (3H, s), a 1.88 (2H, Sextus., J=6.3 Hz), a 1.08 (3H, t, J=6.3 Hz).

Example 194

1,82 g (E)-3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)-2-propen-1-she obtained in example 193, was dissolved in 50 ml of methanol. To the mixture was added 200 mg of 5% palladium-on-carbon in powder form and the mixture is stirred in hydrogen atmosphere at room temperature for 2 hours. The catalyst was then removed by means of filtration. The filtrate was diluted with 100 ml of methanol was added 500 mg of 10% palladium-on-carbon in powder form. The mixture was stirred in hydrogen atmosphere at room temperature for 3 hours. The catalyst was removed via filtration and the solvent was removed under reduced pressure. To the residue was added diisopropyl ether for crystallization to obtain 0,78 g of colorless powdery 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), 7,55 (1H, d, J=2.1 Hz), 7,53 (1H, DD, J=8,1, 2,1 Hz), 7,42 (1H, DDD, J=8,1, to 7.5, 1.8 Hz), 7,40 (1H, s), 6,97 (1H, TD, J=7,5, and 0.9 Hz), 6,93 (1H, userd, J=8.1 Hz), 6.89 in (1H, d, J=8.1 Hz), was 4.02 (2H, t, J=6.6 Hz), of 3.94 (3H, s), of 3.43 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), a 1.88 (2H, Sextus., J=6.6 Hz), of 1.06 (3H, t, J=6.6 Hz).

Example 195

Using 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-it, the floor is built in example 194, 67 mg of colorless powdery 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-she's got in the same way as in example 102.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), to 7.59-7,40 (4H, m), 6,97 (1H, t, J=7.8 Hz), 6,94 (1H, d, J=7.8 Hz), 6,91 (1H, d, J=7.8 Hz), 4,18 (2H, q, J=6.6 Hz), was 4.02 (2H, t, J=6.6 Hz), to 3.92 (3H, s), of 3.43 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), to 1.87 (2H, Sextus., J=6.6 Hz), for 1.49 (3H, t, J=6.6 Hz), of 1.06 (3H, t, J=6.6 Hz).

Example 196

Using 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-she obtained in example 194, 67 mg of colorless, oily 3-[2-(3-cyclopentyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-she's got in the same way as in example 102.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,5, 1.8 Hz), 7,55 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,42 (1H, ushort, J=7.5 Hz), 7,39 (1H, s), 6,97 (1H, t, J=7.5 Hz), 6,93 (1H, d, J=7.5 Hz), 6.89 in (1H, d, J=8,4 Hz), 4,90-4,84 (1H, m), was 4.02 (2H, t, J=6.6 Hz), 3,88 (3H, s), of 3.43 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), 2,03 is 1.60 (10H, m)of 1.05 (3H, t, J=7.2 Hz).

Example 197

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-he obtained in example 194, colorless, oily 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-he was received in the same manner as in example 102.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, and 2.1 Hz), 7,54 (1H, d, J=2.1 Hz), 7,42 (1H, DDD, J=8,4, to 7.2, 1.8 Hz), 7,39 (1H, s), 6,97 (1H, ushort, J=7,2 Hz), of 6.96 (1H, userd, J=8,4 Hz, 6,91 (1H, d, J=8,4 Hz)and 4.65 (1H, Sept., J=6.0 Hz), was 4.02 (2H, t, J=7.2 Hz), 3,90 (3H, s), of 3.43 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), to 1.87 (2H, Sextus., J=7,2 Hz), of 1.40 (6H, d, J=6.0 Hz), of 1.06 (3H, t, J=7.2 Hz).

Example 198

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-he obtained in example 194, colorless powdery 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-he was received in the same manner as in example 102.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), to 7.50 (1H, d, J=1,8 Hz), 7,45-7,39 (2H, m), 6,97 (1H, ushort, J=7.5 Hz), 6,93 (1H, userd, J=7.5 Hz), 6,91 (1H, userd, J=8,4 Hz), was 4.02 (2H, t, J=6.6 Hz), to 3.92 (2H, d, J=7,2 Hz), to 3.92 (3H, s), of 3.43 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), to 1.87 (2H, Sextus., J=6.6 Hz), 1.41 to to 1.32 (1H, m)of 1.06 (3H, t, J=6.6 Hz), 0,69 to 0.63 (2H, m), and 0.40 and 0.35 (2H, m).

Example 199

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-he obtained in example 194, 3-[2-(3-(3-butenyloxy)-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-it is in the form of colorless needle-like crystals were obtained in the same manner as in example 102.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,7, 1.5 Hz), 7,58 (1H, DD, J=8,5, 2.0 Hz), 7,52 (1H, d, J=2.0 Hz), 7,42 (1H, DDD, J=7,7, to 7.5, 1.8 Hz), 7,40 (1H, s), 6,97 (1H, DDD, J=7,7, to 7.5, 0.9 Hz), 6,93 (1H, userd, J=7,7 Hz)6,91 (1H, d, J=8.5 Hz), of 5.92 (1H, DDT, J=17,3, 10,3, 6,8 Hz), 5,19 (1H, DDD, J=17,3, 3,3, 1.5 Hz), 5,11 (1H, DDD, J=10,3, 3,3, 0.6 Hz), 4,14 (2H, t, J=7.2 Hz), was 4.02 (2H, t, J=7.2 Hz), 3,91 (3H, s), of 3.43 (2H, t, J=7.2 Hz), 2,99 (2H,, t, J=7.2 Hz), 2.63 in (2H, userc, J=6.9 Hz), 1,87 (H, Sextus., J=7,2 Hz), of 1.06 (3H, t, J=7.2 Hz).

Example 200

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-he obtained in example 194, 3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-it is in the form of colorless needle-like crystals were obtained in the same manner as in example 102.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,7, 1.8 Hz), to 7.59 (1H, DD, J=8,5, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,42 (1H, DDD, J=8,3, to 7.7, 1.8 Hz), 7,40 (1H, s), 6,97 (1H, TD, J=7,7, 1.1 Hz), 6,93 (1H, userd, J=8,3 Hz)6,91 (1H, d, J=8.5 Hz), 6,12 (1H, DDT, J=17,3, to 10.5, 5.5 Hz), 5,44 (1H, DDD, J=17,3, 3,0, 1.5 Hz), 5,31 (1H, DDD, J=10,5, 3,0, 1.5 Hz), of 4.67 (2H, dt, J=5,5, 1.5 Hz), was 4.02 (2H, t, J=6.3 Hz), to 3.92 (3H, s), of 3.43 (2H, t, J=7.2 Hz), 2,99 (2H,, t, J=7.2 Hz), to 1.87 (2H, Sextus., J=6.3 Hz), of 1.06 (3H, t, J=6.3 Hz).

Example 201

Using 0.1 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-she obtained in example 194, 67 mg of colorless powdery 3-[2-(3-cyclobutylmethyl-4-methoxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-she's got in the same way as in example 111.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), 7,56 (1H, DD, J=7,8, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,45-7,40 (2H, m), 6,98 (1H, t, J=7.8 Hz), 6,94 (1H, d, J=7.8 Hz), make 6.90 (1H, d, J=7.8 Hz), 4,07 (2H, d, J=6.9 Hz), as 4.02 (2H, t, J=6.6 Hz), 3,90 (3H, s), 3,44 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), of 2.86 (1H, Quint., J=7,2 Hz), 2.21 are of 2.16 (2H, m), 1,96-of 1.84 (6H, m)of 1.06 (3H, t, J=7.5 Hz).

Example 202

Using 2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-carbaldehyde obtained in reference p is the iMER 65, pale yellow oily (E)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-1-(2-propoxyphenyl)-2-propen-1-he was received in the same manner as in example 193.

1H-NMR (CDCl3) δ: 7,83 (1H, d, J=15,0 Hz), 7,81 (1H, s), 7,76 (1H, DD, J=8,4, and 2.1 Hz), 7,69 (1H, DD, J=7,8, 1.8 Hz), 7,69 (1H, d, J=2.1 Hz), to 7.50 (1H, d, J=15,0 Hz), was 7.45 (1H, DDD, J=8,4, and 7.8, 1.8 Hz), 7,01 (1H, ushort, J=8,4 Hz), of 6.99 (1H, d, J=8,4 Hz), 6,98 (1H, userd, J=7.8 Hz), to 4.46 (2H, q, J=8,4 Hz)4,06 (2H, t, J=6.3 Hz), of 3.94 (3H, s), 1,90 (2H, Sextus., J=6.3 Hz), of 1.09 (3H, t, J=6.3 Hz).

Example 203

Using (E)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-1-(2-propoxyphenyl)-2-propen-1-he obtained in example 202, colorless powdery 3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-1-(2-propoxyphenyl)propane-1-he was received in the same manner as in example 194.

1H-NMR (DMSO-d6) δ: 7,83 (1H, s), a 7.62 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57 (1H, DD, J=7,8, 1.5 Hz), 7,55 (1H, d, J=1.5 Hz), 7,51 (1H, ushort, J=7.8 Hz), 7,17 (1H, d, J=7.8 Hz), to 7.15 (1H, d, J=7.8 Hz), 7,01 (1H, t, J=7.8 Hz), 4,80 (2H, q, J=9.0 Hz), 4,06 (2H, t, J=6.6 Hz), 3,86 (3H, s)to 3.33 (2H, t, J=7.2 Hz), 2,84 (2H, t, J=7.2 Hz), to 1.79 (2H, Sextus., J=6.6 Hz), 0,99 (3H, t, J=6.6 Hz).

Example 204

Using 2-(3,4-dioxyphenyl)oxazol-4-carbaldehyde obtained in reference example 66, pale yellow powder (E)-3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)-2-propen-1-he was received in the same manner as in example 193.

1H-NMR (CDCl3) δ: 7,81 (1H, d, J=15,0 Hz), 7,79 (1H, userd, J=7.5 Hz), to 7.68 (1H, DD, J=7,8, 1.8 Hz), a 7.62 (1H, d,J=1.8 Hz), to 7.59 (1H, users), 7,49 (1H, d, J=15,0 Hz), 7,44 (1H, ushort, J=7.5 Hz), 7,01 (1H, ushort, J=7.5 Hz), 6,97 (1H, userd, J=7.5 Hz), 6,93 (1H, d, J=7.8 Hz), 4,18 (2H, q, J=6.9 Hz), of 4.16 (2H, q, J=6.9 Hz), of 4.05 (2H, t, J=6,3 Hz), 1,89 (1H, usernext., J=6.9 Hz), 1,50 (3H, t, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz), of 1.09 (3H, t, J=7.2 Hz).

Example 205

Using (E)-3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)-2-propen-1-he obtained in example 204, colorless powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-propoxyphenyl)propane-1-he was received in the same manner as in example 194.

1H-NMR (CDCl3) δ: 7,60 (1H, DD, J=7,8, 1.8 Hz), 7,54 (1H, DD, J=8,4, and 2.1 Hz), 7,52 (1H, d, J=2.1 Hz), 7,42 (1H, DDD, J=7,8, 7,2, 1.8 Hz), 7,39 (1H, s), 6,97 (1H, TD, J=7,8, 1.2 Hz), 6,93 (1H, userd, J=7,2 Hz), make 6.90 (1H, d, J=and 8.4 Hz), 4,17 (2H, q, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), was 4.02 (2H, t, J=6.6 Hz), of 3.43 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), to 1.87 (2H, Sept., J=6.6 Hz), to 1.48 (6H, t, J=6.9 Hz), of 1.05 (3H, t, J=6.6 Hz).

Example 206

Using 2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-carbaldehyde obtained in reference example 64, pale yellow powder (E)-3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)-2-propen-1-he was received in the same manner as in example 193.

1H-NMR (CDCl3) δ: 7,79 (1H, s), 7,79 (1H, d, J=15.3 Hz), 7,69-the 7.65 (3H, m), 7,50-to 7.32 (7H, m), 7.03 is-to 6.95 (3H, m), a total of 5.21 (2H, s), of 4.66 (1H, Sept., J=6.0 Hz), of 3.94 (3H, s)of 1.41 (6H, d, J=6.0 Hz).

Example 207

Using (E)-3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)-2-propen-1-he obtained in example 206, colorless on osteopathy 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he got the same way as in example 194.

1H-NMR (CDCl3) δ: to 7.67 (1H, DD, J=7,5, 1.8 Hz), 7,55 (1H, users), 7,54 (1H, DD, J=7,5, 1.8 Hz), 7,40 (1H, TD, J=7,5, 1.8 Hz), 7,40 (1H, s), to 6.95 (1H, ushort, J=7.5 Hz), 6,93 (1H, userd, J=7.5 Hz), 6.89 in (1H, d, J=7.5 Hz), 5,64 (1H, ), and 4.68 (1H, Sept., J=6.0 Hz), of 3.94 (3H, s), 3,40 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), of 1.40 (6H, d, J=6.0 Hz).

The above compound was also obtained in the following way. 10 g of 2-(3-benzyloxy-4-methoxyphenyl-4-chlorothioxanthone obtained in reference example 5, and 5.4 g of 1-(2-isopropoxyphenyl)ethanone was dissolved in 100 ml of tetrahydrofuran, and to the mixture was added to 2.42 g of sodium hydride. After foaming, the reaction mixture was heated and boiled under reflux for 3 hours. After cooling, the reaction mixture was added to ice water and was carried out by extraction with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to obtain 4,30 g of pale yellow oily 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-it. Then 1,84 obtained 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-it was dissolved in 100 ml of methanol. To the mixture was added 800 mg of 10% palladium-on-carbon in powder form. The mixture was stirred in hydrogen atmosphere at room temperature for 1 the Asa. The catalyst was removed via filtration and the solvent was removed. The residue is then recrystallized from a mixture of acetone/diisopropyl ether to obtain to 1.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-it.

Example 208

Using 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-she obtained in example 207, 0.12 g of pale yellow oily 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-she's got in the same way as in example 102.

1H-NMR (CDCl3) δ: to 7.67 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,41 (1H, TD, J=7,8, 1.8 Hz), 7,39 (1H, s), to 6.95 (1H, ushort, J=7.8 Hz), 6,93 (1H, userd, J=7,8 Hz)6,91 (1H, d, J=8,4 Hz), and 4.68 (1H, Sept., J=6.0 Hz), 3,92 (2H, d, J=6,9 Hz)to 3.92 (3H, s)to 3.41 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), of 1.40 (6H, d, J=6.0 Hz), 1,46-1,32 (1H, m), 0,69-of 0.62 (2H, m), and 0.40 and 0.35 (2H, m).

Example 209

Using 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-she obtained in example 207, 42 mg of colorless powdery 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-she's got in the same way as in example 102.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=7,7, 1.8 Hz), EUR 7.57 (1H, DD, J=8,5, 2.0 Hz), 7,52 (1H, d, J=2.0 Hz), 7,41 (1H, TD, J=7,7, 1.8 Hz), 7,40 (1H, s), to 6.95 (1H, ushort, J=7,7 Hz)6,94 (1H, userd, J=7,7 Hz)6,91 (1H, d, J=8.5 Hz), 4,69 (1H, Sept., J=6.0 Hz), 4,18 (2H, q, J=6.9 Hz), to 3.92 (3H, s)to 3.41 (2H, t, J=6,GC), to 2.99 (2H, t, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz), of 1.40 (6H, d, J=6.0 Hz).

Example 210

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he obtained in example 207, pale yellow oily 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he was received in the same manner as in example 102.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57 (1H, DD, J=7,5, 1.8 Hz), 7,54 (1H, d, J=1,8 Hz), 7,44-7,38 (2H, m), to 6.95 (1H, ushort, J=7.5 Hz), 6,94 (1H, d, J=7.5 Hz), 6,91 (1H, d, J=7.5 Hz), of 4.67 (2H, Sept., J=6.0 Hz), 3,90 (3H, s), 3,40 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), of 1.40 (12H, d, J=6.0 Hz).

Example 211

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he obtained in example 207, colorless, oily 3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he was received in the same manner as in example 102.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=7,7, 1.8 Hz), 7,58 (1H, DD, J=8,3, 1.8 Hz), 7,53 (1H, d, J=1,8 Hz), 7,41 (1H, DDD, J=7,9, and 7.7, 1.8 Hz), 7,40 (1H, s), 6,98 (1H, TD, J=7,9, 1.8 Hz), 6,94 (1H, userd, J=7,7 Hz), 6,92 (1H, d, J=8,3 Hz), 6,12 (1H, DDT, J=17,3, 10,5, a 5.3 Hz), 5,44 (1H, DDD, J=17,3, 3,0, 1.7 Hz), 5,31 (1H, DDD, J=10,5, 3,0, 1.5 Hz), 4.75 V-4,60 (3H, m)to 3.92 (3H, s)to 3.41 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), of 1.40 (6H, d, J=6,0 Hz).

Example 212

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he obtained in example 207, 3-[2-(3-(3-butenyloxy)-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-W is colored needle-shaped crystals were obtained in the same way, as in example 102.

1H-NMR (CDCl3) δ: to 7.67 (1H, DD, J=7,9, 1.8 Hz), EUR 7.57 (1H, DD, J=8,5, 2.0 Hz), 7,53 (1H, d, J=2.0 Hz), 7,40 (1H, DDD, J=7,9, and 7.5, 1.8 Hz), 7,40 (1H, s), to 6.95 (1H, ushort, J=7.5 Hz), 6,93 (1H, userd, J=7.5 Hz), 6,91 (1H, d, J=8,5 Hz), of 5.92 (1H, DDT, J=17.1 to, 10,3, 6,8 Hz), 5,19 (1H, DDD, J=17,3, 3,3, 1.5 Hz), 5,10 (1H, DDD, J=10,3, 3,3, 1.3 Hz), and 4.68 (1H, Sept., J=6.0 Hz), 4,14 (2H, t, J=7.2 Hz), 3,91 (3H, s)to 3.41 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), 2.63 in (2H, userc, J=7,2 Hz), of 1.40 (6H, d, J=6.0 Hz).

Example 213

Using 0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-she obtained in example 207, 40 mg of a colorless powder of 1-(2-isopropoxyphenyl)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propane-1-she's got in the same way as in example 111.

1H-NMR (CDCl3) δ: 7,70-of 7.60 (2H, m), 7,44-7,38 (2H, m), 6,98-6,91 (4H, m), 4,69 (1H, Sept., J=6.0 Hz), 4,48-to 4.41 (2H, m), 3,93 (3H, s), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), of 1.41 (6H, d, J=6.0 Hz).

Example 214

Using 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he obtained in example 207, colorless powdery 3-[2-(3-cyclobutylmethyl-4-methoxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he was received in the same manner as in example 111.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=8,4, 1.8 Hz), 7,56 (1H, DD, J=8,4, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,44-7,38 (2H, m), to 6.95 (1H, ushort, J=8,4 Hz)6,94 (1H, userd, J=8,4 Hz), make 6.90 (1H, d, J=8,4 Hz), 4,69 (1H, Sept., J=6.0 Hz), 4,07 (2H, d, J=6.9 Hz), 3,90 (3H, s)to 3.41 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), 2,86 (1H, Queen is., J=7,2 Hz), 2,22 with 2.14 (2H, m), 1,99-of 1.84 (4H, m)of 1.40 (6H, d, J=6.0 Hz).

Example 215

Using 2-(3,4-dioxyphenyl)oxazol-4-carbaldehyde obtained in reference example 66, yellow oily (E)-3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)-2-propen-1-he was received in the same manner as in example 193.

1H-NMR (CDCl3) δ: 7,81 (1H, d, J=15.3 Hz), 7,79 (1H, users), 7,69-7,53 (3H, m), 7,46 (1H, d, J=15.3 Hz), the 7.43 (1H, TD, J=7,8, 1.2 Hz), 7,00 (1H, ushort, J=7.8 Hz), 6,93 (1H, userd, J=7,8 Hz)6,91 (1H, userd, J=7.8 Hz), of 4.67 (1H, Sept., J=6.0 Hz), 4,22-4,11 (4H, m), 1,52-of 1.45 (6H, m)of 1.41 (6H, d, J=6.0 Hz).

Example 216

Using (E)-3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)-2-propen-1-he obtained in example 215, pale yellow oily 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-isopropoxyphenyl)propane-1-he was received in the same manner as in example 194.

1H-NMR (CDCl3) δ: to 7.67 (1H, DD, J=7,5, 1.5 Hz), 7,60-7,38 (4H, m), 6,97-6,89 (3H, m), and 4.68 (1H, Sept., J=6.0 Hz), 4,21-4,10 (4H, m)to 3.41 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), to 1.48 (6H, ushort, J=7,2 Hz), of 1.40 (6H, d, J=6.0 Hz).

Example 217

Using 2-(3,4-dioxyphenyl)oxazol-4-carbaldehyde obtained in reference example 66, colorless powder (E)-3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-o-tolyl-2-propen-1-he was received in the same manner as in example 193.

1H-NMR (CDCl3) δ: 7,81 (1H, s)of 7.64-7,28 (8H, m), 6,93 (1H, d, J=8.1 Hz), 4,20 (2H, q, J=6.9 Hz), of 4.16 (2H, q, J=6.9 Hz), 2,47 (3H, s)of 1.50 (3H, t, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz).

Example 218

Use the Zuya (E)-3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-o-tolyl-2-propen-1-it, obtained in example 217, 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-it is in the form of colorless needle-like crystals were obtained in the same manner as in example 194.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=7,5, 1.8 Hz), 7,55 (1H, DD, J=8,1, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), the 7.43 (1H, users), was 7.36 (1H, TD, J=7,5, 1.5 Hz), 7,27-7,22 (2H, m), 6.90 to (1H, d, J=8.1 Hz), 4,17 (2H, q, J=6.9 Hz), 4,14 (2H,, kV, J=6.9 Hz), 3,32 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2.49 USD (3H, s)to 1.48 (6H, t, J=6.9 Hz).

Example 219

Using 2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-carbaldehyde obtained in reference example 64, pale yellow powder (E)-3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolyl-2-propen-1-he was received in the same manner as in example 193.

1H-NMR (CDCl3) δ: 7,81 (1H, s), 7,69-7,26 (13H, m), of 6.96 (1H, d, J=9.0 Hz), 5,23 (2H, s), of 3.94 (3H, s), 2,47 (3H, s).

Example 220

Using (E)-3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolyl-2-propen-1-he obtained in example 219, colorless powdery 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-he was received in the same manner as in example 194.

1H-NMR (CDCl3) δ: to 7.67 (1H, DD, J=7,2, 1.8 Hz), 7,56 (1H, d, J=1,8 Hz), 7,53 (1H, DD, J=8,1, 1.8 Hz), the 7.43 (1H, s), 7,35 (1H, TD, J=7,2, 1.8 Hz), 7,26-7,22 (2H, m), 6.89 in (1H, d, J=8.1 Hz), 5,69 (1H, s), of 3.94 (3H, s), 3,31 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2.49 USD (3H, s).

Example 221

0.15 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-she obtained in example 220, was dissolved in 10 ml isopropylate what about alcohol. To the mixture was added 86 μl (methyl bromide)cyclopropane and 200 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene and the mixture was heated and boiled under reflux for 24 hours. To the reaction mixture were added water and then carried out the extraction with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) and recrystallized from a mixture of acetone/diisopropyl ether/n-hexane to obtain 71 mg of 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-it is in the form of colorless needle-like crystals.

1H-NMR (CDCl3) δ: to 7.68 (1H, DD, J=7,5, 1.5 Hz), EUR 7.57 (1H, DD, J=8,1, 2,1 Hz), 7,49 (1H, d, J=2.1 Hz), the 7.43 (1H, t, J=0.9 Hz), was 7.36 (1H, TD, J=7,5, 1.5 Hz), 7,25-7,22 (2H, m)6,91 (1H, d, J=8.1 Hz), 3,93 (2H, d, J=6,9 Hz), to 3.92 (3H, s), of 3.32 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2.49 USD (3H, s), 1.41 to to 1.32 (1H, m), is 0.69 to 0.63 (2H, m), and 0.40 and 0.35 (2H, m).

Example 222

Using 2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-carbaldehyde obtained in reference example 69, yellow powder (E)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-benzyloxyphenyl)-2-propen-1-he was received in the same manner as in example 193.

1H-NMR (CDCl3) δ: 7,76 (1H, s), 7,69-6,92 (14H, m), 5,20 (2H, s), 4,63 (1H, Sept., J=6.0 Hz), to 1.38 (6H, d, J=6.0 Hz).

Example 223

Using (E)-3-[2-(3-isopropoxy-4-IU is oxyphenyl)oxazol-4-yl]-1-(2-benzyloxyphenyl)-2-propen-1-it, obtained in example 222, colorless plastinchatoklyuvye 1-(2-hydroxyphenyl)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-he was received in the same manner as in example 194.

1H-NMR (CDCl3) δ: 12,25 (1H, s), 7,82 (1H, DD, J=8,4, 1.5 Hz), 7,58 (1H, DD, J=8,4, 1.8 Hz), 7,54 (1H, d, J=1,8 Hz), 7,46 (1H, DDD, J=8,4, to 7.2, 1.5 Hz), 7,45 (1H, s), 6,98 (1H, DD, J=8,4, 1.2 Hz), 6,92 (1H, d, J=8,4 Hz), 6.89 in (1H, DDD, J=8,4, to 7.2, 1.2 Hz)and 4.65 (1H, Sept., J=6.0 Hz), 3,90 (3H, s), 3,44 (2H, t, J=7.5 Hz), 3,03 (2H, t, J=7.5 Hz), of 1.40 (6H, d, J=6.0 Hz).

Example 224

67 mg of 1-(2-hydroxyphenyl)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-she obtained in example 223, was dissolved in 5 ml of dimethylformamide. To the mixture was added 31 μl of allylbromide and 73 mg of potassium carbonate and the mixture was stirred at room temperature overnight. To the mixture was again added 50 μl of allylbromide and the mixture was stirred at 50°C for 8 hours and at room temperature over night. The reaction mixture was added to water and then carried out the extraction with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) and was led from n-hexane to obtain 33 mg of a colorless powder of 1-(2-allyloxyphenyl)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, and 2.1 Hz), 7,54 (1H, d, J=2.1 Hz), 7,44 (1H, DDD, J=7,8, and 7.5, 1.8 Hz), 7,40 (1H, users), of 6.99 (1H, TD, J=7,8, 1.2 Hz), 6,94 (1H, userd, J=7.5 Hz), 6,91 (1H, d, J=and 8.4 Hz), between 6.08 (1H, DDT, J=17.1 to, 10,5, a 5.4 Hz), 5,42 (1H, DDD, J=17.1 to, 3,0, 1.5 Hz), from 5.29 (1H, DDD, J=10,5, 2.7, and 1.5 Hz), 4,69-br4.61 (3H, m)to 3.89 (3H, s), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), of 1.39 (6H, d, J=6,3 Hz).

Example 225

Using 0.3 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-she obtained in example 220, 0.15 g of white powdery 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-she's got in the same way as in example 3.

1H-NMR (CDCl3) δ: 7.68 per (1H, m), EUR 7.57 (1H, DD, J=8,1, 2,1 Hz), 7,51 (1H, d, J=2.1 Hz), 7,44 (1H, d, J=0.9 Hz), was 7.36 (1H, m), 7,30-7,20 (3H, m)6,91 (1H, d, J=8,4 Hz), 4,18 (2H, q, J=6.9 Hz), to 3.92 (3H, s), 3,35-of 3.25 (2H,, m), 3,05-2,95 (2H, m)of 2.50 (3H, s)of 1.50 (3H, t, J=6.9 Hz).

Example 226

Using 0.3 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-she obtained in example 220, 0.1 g of white powdery 3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-she's got in the same way as in example 3.

1H-NMR (CDCl3) δ: 7.68 per (1H, m), to 7.59 (1H, DD, J=8,4, and 2.1 Hz), 7,52 (1H, d, J=2.1 Hz), the 7.43 (1H, s), 7,38 (1H, m), 7,35-of 7.25 (2H, m), 6,92 (1H, d, J=8,4 Hz), 6,13 (1H, DDD, J=17.1 to, 10,5, a 5.4 Hz), 5,44 (1H, DDD, J=17.1 to, 2.7, and 1.5 to Hz), 5,31 (1H, DDD, J=10,5, 2.7, and 1.5 Hz), and 4.68 (1H, dt, J=5,4, 1.5 Hz), to 3.92 (3H, s), of 3.32 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2,50 (3H, s).

Example 227

Using 0.2 g of 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-the l]-1-o-tolylpropan-1-it, obtained in example 220, 0.1 g of pale yellow oily 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-1-o-tolylpropan-1-she's got in the same way as in example 3.

1H-NMR (CDCl3) δ: of 7.69 (1H, m), 7,60 is 7.50 (2H, m), 7,50-7,30 (3H, m), 7,24 (1H, m)6,91 (1H, DD, J=5,1, 3,0 Hz)and 4.65 (1H, m), 3,90 (3H, s), 3,35-of 3.25 (2H, m), 3,05-2,95 (2H, m), 2.49 USD (3H, s)of 1.40 (6H, d, J=6.0 Hz).

Example 228

65 mg of sodium hydride suspended in 5 ml of tetrahydrofuran. To the mixture was sequentially added 0.27 g of 1-(2-ethoxyphenyl)ethanone and 0.3 g of 2-(3-benzyloxy-4-deformational)-4-chlorothioxanthone obtained in reference example 44, with ice cooling and stirring and the mixture was stirred for 3 hours under heating and boiling under reflux. To the reaction mixture were added saturated aqueous solution of ammonium chloride under ice cooling and stirring. After stirring for 15 minutes, to the mixture was added water and was carried out by extraction with ethyl acetate. The mixture was dried over anhydrous magnesium sulfate and the solvent was removed. The obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 4:1) to give 75 mg of colorless, oily 3-[2-(3-benzyloxy-4-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: 7,72-of 7.69 (2H, m), to 7.59 (1H, DD, J=8,1, 1.8 Hz), 7,47-to 7.32 (7H, m), 7,00-6,92 (3H, m), is 6.61 (1H, t, J=74,7 Hz), 5,20 (2H, s), is 4.15 (2H, q, J=7.2 Hz), of 3.43 (2H, t, J=7 Hz), of 3.00 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Example 229

75 mg of 3-[2-(3-benzyloxy-4-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-she obtained in example 228, dissolved in 1 ml ethanol. To the mixture was added 7 mg of 10% palladium-on-carbon in powder form and the mixture is stirred in hydrogen atmosphere at room temperature for 45 minutes. The catalyst was removed through filtration, the filtrate was concentrated and the obtained residue was purified column chromatography on silica gel (dichloromethane:ethanol = 100:1) to give 32 mg of white powdery 3-[2-(4-deformedarse-3-hydroxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,5, 1.8 Hz), the 7.65 (1H, d, J=1,8 Hz), 7,56-the 7.43 (3H, m), 7,16 (1H, d, J=6.0 Hz), 6,98-6,92 (2H, m), to 6.57 (1H, t, J=74,7 Hz), to 5.57 (1H, s), of 4.13 (2H, q, J=7.2 Hz), 3,42 (2H, t, J=7.2 Hz), to 3.00 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Example 230

30 mg of 3-[2-(4-deformedarse-3-hydroxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-she obtained in example 229, was dissolved in 0.5 ml of dimethylformamide. To the mixture was added 18 mg of 2-bromopropane and 30 mg of potassium carbonate and the mixture was stirred at room temperature overnight. To the reaction mixture was added water and was carried out by extraction with ethyl acetate. Was carried out by drying using anhydrous magnesium sulfate and the solvent was removed. The obtained residue was purified column chromatography on silicagel the (n-hexane:ethyl acetate = 4:1) to give 23 mg of white powdery 3-[2-(4-deformedarse-3-isopropoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), to 7.61 (1H, d, J=1,8 Hz), 7,55 (1H, DD, J=8,4, 1.8 Hz), 7,50-7,38 (2H, m), 7,19 (1H, d, J=8.1 Hz), 7,00-6,70 (2H, m), 6,60 (1H, t, J=74,7 Hz), 4.72 in with 4.64 (1H, m), of 4.13 (2H, q, J=7,2 Hz), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz), of 1.39 (6H, d, J=6.0 Hz).

Example 231

Using 2-(3-benzyloxy-4-methoxyphenyl)-4-chlorothioxanthone obtained in reference example 5 and 1-(2-methoxyethoxymethyl)ethanone obtained in reference example 70, yellow oily 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyethoxymethyl)propane-1-he was received in the same manner as in example 190.

1H-NMR (CDCl3) δ: 7,66 (1H, DD, J=7,8, 1.8 Hz), to 7.59 (1H, DD, J=7,8, 1.8 Hz), 7,51 (1H, users), 7,49-7,27 (7H, m), 7,17 (1H, userd, J=7.8 Hz),? 7.04 baby mortality (1H, TD, J=7,5, 1.2 Hz), 6,93 (1H, userd, J=7,8 Hz in), 5.25 (2H, s), 5,19 (2H, s), 3,92 (3H, s), of 3.48 (3H, s), 3,39 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz).

Example 232

Using 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyethoxymethyl)propane-1-she obtained in example 231, 3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyethoxymethyl)propane-1-he was received in the same manner as in example 194.

1H-NMR (CDCl3) δ: 7,66 (1H, DD, J=7,8, 1.8 Hz), 7,55 (1H, d, J=2.1 Hz), 7,53 (1H, DD, J=8,1, 2,1 Hz), 7,41 (1H, s), 7,41 (1H, DDD, J=7,8, and 7.5, 1.8 Hz), 7,17 (1H, userd, J=7.8 Hz),? 7.04 baby mortality (1H, TD, J=7,5, 0.8 Hz), 6.89 in (1H, d, J=8.1 Hz), 5,64 (1H, s), of 5.26 (2H, s), of 3.94 (3H, s), 3,49 (3H, s), 3,40 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz).

Example 233

Using 3-[2-(3-hydroxy-4-methoxy who enyl)oxazol-4-yl]-1-(2-methoxyethoxymethyl)propane-1-it, obtained in example 232, colorless, oily 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-methoxyethoxymethyl)propane-1-he was received in the same manner as in example 102.

1H-NMR (CDCl3) δ: 7,66 (1H, DD, J=7,5, 1.8 Hz), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), 7,53 (1H, d, J=1,8 Hz), 7,42 (1H, DDD, J=8,4, to 7.5, 1.8 Hz), 7,41 (1H, s), 7,17 (1H, DD, J=8,4, 1.2 Hz),? 7.04 baby mortality (1H, TD, J=7,5, 1.2 Hz), 6,91 (1H, d, J=8,4 Hz), of 5.26 (2H, s), with 4.64 (1H, Sept., J=6.0 Hz), 3,90 (3H, s), 3,49 (3H, s), 3,40 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), of 1.39 (6H, d, J=6.0 Hz).

Example 234

Using 0,76 g of 4-chloromethyl-2-(3-ethoxy-4-methoxyphenyl)oxazole obtained in reference example 58, 60 mg of white powdery 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-[2-(2,2,2-triptoreline)phenyl]propane-1-she's got in the same way as in example 228.

1H-NMR (CDCl3) δ: 7,76 (1H, DD, J=7,8, and 2.1 Hz), 7,58-of 7.48 (3H, m), 7,39 (1H, s), 7,12 (1H, t, J=7.5 Hz), 6,92-to 6.88 (2H, m), to 4.46 (2H, q, J=7.8 Hz), 4,18 (2H, q, J=7.2 Hz), to 3.92 (3H, s), 3,40 (2H, t, J=7.5 Hz), of 3.00 (2H,, t, J=7.5 Hz), for 1.49 (3H, t, J=7.2 Hz).

Example 235

Using 0,76 g of 4-chloromethyl-2-(3-ethoxy-4-methoxyphenyl)oxazole obtained in reference example 58, and of 0.58 g of 1-(2-trifloromethyl)ethanone 0.18 g of pale yellow oily 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-trifloromethyl)propane-1-she's got in the same way as in example 228.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,5, 1.8 Hz), 7,58 is 7.50 (3H, m), 7,42 (1H, s), 7,38-7,30 (2H, m)6,91 (1H, d, J=8,4 Hz)to 4.17 (2H, q, J=6.6 Hz), 3,91 (3H, s), of 3.45 (2H, t, J=7,2 Hz), a 3.01 (2H, t, J=7.2 Hz), for 1.49 (3H, t, J=6.6 Hz).

Example 236

Using 0.5 g of 3-[2-(3,4-acid)oxazol-4-yl]propionic acid obtained in reference example 71, 0.32 g of white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-pyrrolidin-1-improper-1-she's got in the same way as in example 1.

1H-NMR (CDCl3) δ: at 7.55 (1H, DD, J=6.75 in, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,44 (1H, s)6,91 (1H, d, J=8.1 Hz), 4,20-4,10 (4H, m), 3,50 is 3.40 (4H, m), 3.00 and-2,90 (2H, m), 2,70-2,60 (2H, m), 1,95 is 1.75 (4H, m)to 1.48 (3H, t, J=7,2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Example 237

Using 0.3 g of 3-[2-(3,4-acid)oxazol-4-yl]propionic acid obtained in reference example 71, 0.28 g of white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(3-hydroxypyrrolidine-1-yl)propane-1-she's got in the same way as in example 1.

1H-NMR (CDCl3) δ: at 7.55 (1H, DD, J=6.75 in, 1.8 Hz), 7,52 (1H, d, J=1,8 Hz), 7,44 (1H, s)6,91 (1H, d, J=8.1 Hz), 4,20-4,10 (4H, m), 3,50 is 3.40 (4H, m), 3.00 and-2,90 (2H, m), 2,70-2,60 (2H, m), 2,10-1,90 (3H, m)to 1.48 (3H, t, J=6,9 Hz)to 1.48 (3H, t, J=6.9 Hz).

Example 238

Using 1 g of 3-[2-(4-benzyloxy-3-methoxyphenyl)oxazol-4-yl]propionic acid obtained in reference example 73, of 1.03 g of pale yellow powdery 3-[2-(4-benzyloxy-3-methoxyphenyl)oxazol-4-yl]-1-pyrrolidin-1-improper-1-she's got in the same way as in example 1.

1H-NMR (CDCl3) δ: to 7.61-7,27 (8H, m), 6,93 (1H, d, J=8,4 Hz), 5,20 (2H, s), of 3.97 (3H, s), 3,49-3,39 (4H, m)to 2.94 (2H, t, J=7.5 Hz), to 2.65 (2H, t, J=7,5 Hz), 1,95-of 1.78 (4H, m).

Example 239

Using 1 g of 3-[2-(4-benzyloxy-3-methoxyphenyl)oxazol-4-yl]-1-pyrrolidin-1-improper-1-she obtained in example 238, 0,59 g of white powdery 3-[2-(4-hydroxy-3-methoxyphenyl)oxazol-4-yl]-1-pyrrolidin-1-improper-1-she's got in the same way as in example 2.

1H-NMR (CDCl3) δ: 7,56-7,51 (2H, m), 7,44 (1H, s), make 6.90 (1H, d, J=8,4 Hz), 5,97 (1H, s), of 3.97 (3H, s), 3,49-3,39 (4H, m)to 2.94 (2H, t, J=7.5 Hz), to 2.66 (2H, t, J=7.5 Hz), 1,97-to 1.79 (4H, m).

Example 240

Using 0.15 g of 3-[2-(4-hydroxy-3-methoxyphenyl)oxazol-4-yl]-1-pyrrolidin-1-yl-propane-1-she obtained in example 239, of 0.13 g of white powdery 3-[2-(4-ethoxy-3-methoxyphenyl)oxazol-4-yl]-1-pyrrolidin-1-improper-1-she's got in the same way as in example 3.

1H-NMR (CDCl3) δ: EUR 7.57 (1H, DD, J=8,1, 2,1 Hz), 7,52 (1H, d, J=1,8 Hz), 7,45 (1H, s)6,91 (1H, d, J=8.1 Hz), is 4.15 (2H, q, J=6.9 Hz), of 3.96 (3H, s), 3,49 is 3.40 (4H, m)to 2.94 (2H, t, J=7.2 Hz), to 2.66 (2H, t, J=7.2 Hz), 1,97-to 1.79 (4H, m), for 1.49 (3H, t, J=6.9 Hz).

Example 241

N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-cryptomelane obtained in example 25 was dissolved in 1 ml of dimethylformamide. To the mixture was added 30 mg of sodium hydride under ice cooling and stirring and the mixture was stirred for 30 minutes. To the mixture was added 30 mg under the conditions and the reaction mixture was stirred at room temperature for 2 hours. Then to the mixture were added water and ethyl acetate and implemented the Yali extraction. The organic layer twice washed with water and concentrated by removing the solvent under reduced pressure. The residue was purified by chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to give 35 mg of a colorless oily N-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-ylmethyl]-N-methyl-2-cryptomelane.

1H-NMR (CDCl3) δ: 7,72-7,34 (7H, m)6,94 (1H, DD, J=8,4, 1.8 Hz), 4,88-4,11 (1H, m), 3,98-to 3.89 (5H, m), 3,17-is 2.88 (3H, m), 1,43 is 1.34 (1H, m), 0,71-of 0.64 (2H, m), 0,42-0,36 (2H, m).

Example 242

Using 0.14 g of [2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]methylamine obtained in reference example 74, 70 mg of colorless oily N-[2-(3,4-acid)oxazol-4-ylmethyl]-2-ethoxy-N-methylbenzamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 7,60-7,26 (5H, m), 7,00-6,87 (3H, m), 4,23-was 4.02 (8H, m), 3,19-2,96 (3H, m), 1,52-of 1.40 (6H, m)of 1.36 (3H, t, J=6.9 Hz).

Example 243

Using 0.2 g of 2-[2-(3,4-dioxyphenyl)oxazol-4-yl]ethylamine obtained in reference example 78, and 0.18 g of 2 - ethoxybenzoyl acid, 0.14 g of white powdery N-{2-[2-(3,4-acid)oxazol-4-yl]ethyl}-2-ethoxybenzene was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: by 8.22 (1H, DD, J=7,5, 4,8 Hz), 7,60 is 7.50 (2H, m), 7,47 (1H, s), 7,39 (1H, m), 7,06 (1H, m), 6,95-6,85 (2H, m), 4,30-of 4.05 (6H, m), 4.09 to (2H, q, J=6.9 Hz), 3,85 (2H, q, J=6.6 Hz), only 2.91 (2H, t, J=6,6 Hz), to 1.48 (6H, t, J=6.9 Hz), of 1.28 (6H, t, J=6.9 Hz).

Example 244

With the use of 0.3 is 2-(3,4-dioxyphenyl)oxazol-4-carboxylic acid, obtained in reference example 80, and 0.28 g of 1-(2-amino)ethanone 0.32 g of white powdery N-(2-oxo-2-phenylethyl)-2-(3,4-dioxyphenyl)oxazol-4-carboxamide was obtained in the same manner as in example 1.

1H-NMR (DMSO-d6) δ: 8,67 (1H, d, J=0.9 Hz), 8,49 (1H, t, J=5.7 Hz), 8,10-of 8.00 (2H, m), 7,70-to 7.50 (5H, m), 7,16 (1H, m), to 4.81 (2H, d, J=5.7 Hz), of 4.13 (4H, q, J=6.9 Hz), to 1.38 (6H, t, J=6.9 Hz), of 1.37 (3H, t, J=6.9 Hz).

Example 245

Using 2-(3,4-dioxyphenyl)oxazol-4-carboxylic acid obtained in reference example 80, 0.32 g of a white powder of 1-(4-{4-[2-(3,4-dioxyphenyl)oxazol-4-carbonyl]piperazine-1-yl}phenyl)ethanone was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: to 8.20 (1H, s), 7.95 is-a 7.85 (2H, m), a 7.62 (1H, DD, J=8,4, and 2.1 Hz), 7,54 (1H, d, J=2.1 Hz), 7,00-6,85 (3H, m), 4,40-4,20 (2H, m), 4,19 (2H, q, J=6.9 Hz), of 4.16 (2H, q, J=6.9 Hz), 4,00-of 3.80 (2H, m), 3,50-3,45 (4H, m), of 2.53 (3H, s)of 1.50 (3H, t, J=6.9 Hz), 1,50 (3H, t, J=6.9 Hz).

Example 246

Using 0.28 g of 2-(3,4-dioxyphenyl)oxazol-4-carboxylic acid obtained in reference example 80, and 0.2 g of 1-(4-methoxyphenyl)piperazine 0.36 g of a white powder of 4-(2-(3,4-dioxyphenyl)oxazol-4-yl)-1-(4-methoxyphenyl)piperazine was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,16 (1H, s), to 7.61 (1H, DD, J=8,7, and 2.1 Hz), 7,54 (1H, s), 6,95-6,84 (5H, m), 4,40-4,30 (2H, m), 4,21-4,12 (4H, m), 4,00-3,93 (2H, m), of 3.78 (3H, s), 3,14 (4H, t, J=4,8 Hz)of 1.47 (6H, t, J=7.2 Hz).

Example 247

Using 0.28 g of 2-(3,4-dioxyphenyl)oxazol-4-Carbo the OIC acid, obtained in reference example 80, and 1-(4-hydroxyphenyl)piperazine white powder of 4-(2-(3,4-dioxyphenyl)oxazol-4-yl)-1-(4-hydroxyphenyl)piperazine was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,16 (1H, s), to 7.61 (1H, DD, J=8,7, and 2.1 Hz), 7,54 (1H, s), 6,95-6,78 (5H, m), 4,40-4,30 (2H, m), 4,21-4,12 (4H, m), 4,00-3,93 (2H, m), 3,14 (4H, t, J=4,8 Hz), for 1.49 (6H, t, J=7.2 Hz).

Example 248

Using 0.28 g of 2-(3,4-dioxyphenyl)oxazol-4-carboxylic acid obtained in reference example 80, and 0.14 g of 2-phenethylamine 0.21 g of white powdery N-phenethyl-2-(3,4-acid)oxazol-4-carboxamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,17 (1H, s), 7,56 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=2.1 Hz), of 7.36-7,21 (5H, m), 7,12 (1H, users), 6,93 (1H, d, J=8,4 Hz), 4,22-4,12 (4H, m), 3,74-3,66 (2H, m), 2,95 (2H, t, J=7.2 Hz), 1,57 of 1.46 (6H, m).

Example 249

Using 0.28 g of 2-(3,4-dioxyphenyl)oxazol-4-carboxylic acid obtained in reference example 80, and 0.13 g of 1-(2-amino-ethyl)pyrrolidine 0.15 g of pale yellow powder of N-(2-(pyrrolidin-1-yl)ethyl)-2-(3,4-acid)oxazol-4-carboxamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 8,17 (1H, s), 7,60 (1H, DD, J=8,4, 1.8 Hz), 7,55 (1H, d, J=1,8 Hz), 7,44 (1H, users), 6,92 (1H, d, J=8,4 Hz), 4,23-4,12 (4H, m), 3,65-to 3.58 (2H, m), and 2.79 (2H, t, J=6.6 Hz), 2,70-of 2.58 (4H, m), 1,87 is 1.75 (4H, m), 1,53 of 1.46 (6H, m).

Example 250

Using 0.15 g of [2-(3,4-dioxyphenyl)oxazol-4-yl]acetic to the slots, obtained in reference example 81, and 0.11 g of o-phenetidine 0.12 g of white powdery 2-[2-(3,4-dioxyphenyl)oxazol-4-yl]-N-(2-ethoxyphenyl)ndimethylacetamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: a total of 8.74 (1H, users), of 8.37 (1H, DD, J=7,2, 1.8 Hz), 7,70-the 7.65 (2H, m), to 7.61(1H, d, J=1,8 Hz), 7,00-of 6.90 (3H, m), to 6.80 (1H, DD, J=7,8, 1.2 Hz), 4,18 (2H, q, J=6.9 Hz), of 4.16 (2H, q, J=6.9 Hz), of 3.97 (2H, q, J=7,2 Hz), 3,74(2H, s), for 1.49 (3H, t, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz), of 1.18 (3H, t, J=7.2 Hz).

Example 251

Using 0.15 g of [2-(3,4-dioxyphenyl)oxazol-4-yl]acetic acid obtained in reference example 81, and 85 mg of 2-amino-3-hydroxypyridine 0.11 g of white powdery 2-[2-(3,4-dioxyphenyl)oxazol-4-yl]-N-(3-hydroxypyridine-2-yl)ndimethylacetamide was obtained in the same manner as in example 1.

1H-NMR (CDCl3) δ: 10,37 (1H, users), 9,88 (1H, users), to 7.84 (1H, DD, J=4,8, 1.2 Hz), 7,65-of 7.60 (3H, m), 7,31 (1H, DD, J=4.2, and 1.2 Hz), 6,94 (1H, d, J=9.0 Hz), 4,22 (2H, q, J=6.9 Hz), of 4.16 (2H, q, J=6.9 Hz)and 1.51 (3H, t, J=6,9 Hz), for 1.49 (3H, t, J=6.9 Hz).

Example 252

0.5 g of 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole obtained in reference example 35, 0.36 g piperazine-2-she and 0.28 g of potassium carbonate were added to 10 ml of acetonitrile and the mixture was heated and boiled under reflux for 7 hours. The residue was diluted with ethyl acetate and washed with water and then saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated by removing the solvent is at reduced pressure. The residue was purified column chromatography on silica gel (dichloromethane:methanol = 1:0 to 50:1) and the crude crystals are recrystallized from ethyl acetate to obtain 0.25 g of colorless crystalline 4-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]piperazine-2-it.

1H-NMR (CDCl3) δ: to 7.59 (1H, d, J=8,1, 2,1 Hz), 7,56 (1H, d, J=2.1 Hz), 6,91 (1H, d, J=8.1 Hz), 6,03 (1H, users), to 4.17 (2H, q, J=6.9 Hz), is 4.15 (2H, q, J=6.9 Hz), 3,61 (2H, s), 3.45 points-to 3.35 (2H, m), with 3.27 (2H, s), 2,80-of 2.75 (2H,, m)to 1.48 (6H, t, J=6.9 Hz).

Example 253

Using 0.5 g of 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole obtained in reference example 35, and 0.5 g of the research 0.31 g of white powdery 4-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]the research was obtained in the same manner as in example 252.

1H-NMR (CDCl3) δ: 7,70 is 7.50 (2H, m), 7,54 (1H, s)6,91 (1H, d, J=8,4 Hz), 4,25-4,10 (4H, m), 3,80-3,70 (4H, m), 3,51 (2H, s), 2,60-of 2.50 (4H, m)to 1.48 (6H, t, J=6.9 Hz).

Example 254

0.5 g of 4-chloromethyl-2-(3,4-dioxyphenyl)oxazole obtained in reference example 35, 0.28 g of 2-mercaptopyridine and 0.28 g of potassium carbonate were added to 10 ml of dimethylformamide and the mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with ethyl acetate and washed with water and then with saturated saline. The organic layer was dried over anhydrous magnesium sulfate and concentrated by removing the solvent under reduced pressure. The residue was purified colon is the offered by chromatography on silica gel (ethyl acetate:n-hexane = 1:4 to 1:2) and the obtained crude crystals are recrystallized from a mixture of ethyl acetate and n-hexane to obtain 0,63 g of colorless crystalline 2-[2-(3,4-dioxyphenyl)oxazol-4-elmersolver]pyridine.

1H-NMR (CDCl3) δ: 8,45 (3H, m), 7,60 is 7.50 (3H, m), 7,47 (1H, m), 7,18 (1H, d, J=8.1 Hz), 6,99 (1H, m), 6.89 in (1H, d, J=8.1 Hz), to 4.38 (2H, s)to 4.17 (2H, q, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), 1,47 (6H, t, J=6.9 Hz).

Example 255

of 0.58 g of 2-[2-(3,4-dioxyphenyl)oxazol-4-elmersolver]pyridine obtained in example 254, was added to 20 ml of dichloromethane. To the mixture was gradually added 0.55 g of meta-chloroperbenzoic acid under ice cooling and the mixture is then stirred. The reaction mixture was diluted with 30 ml dichloromethane and washed with 10%aqueous sodium hydroxide solution and then with saturated saline. The organic layer was dried over anhydrous magnesium sulfate and concentrated by removing the solvent under reduced pressure. The residue was purified column chromatography on silica gel (ethyl acetate:n-hexane = 2:1 to 3:1) and the crude crystals are recrystallized from a mixture of ethyl acetate and n-hexane to obtain 0,49 g of colorless crystalline 2-[2-(3,4-dioxyphenyl)oxazol-4-elmersolver]pyridine.

1H-NMR (CDCl3) δ: 8,81 (1H, m), 8,00 (1H, m), to $ 7.91 (1H, m), to 7.61 (1H, s), 7,55 (1H, m), 7,50-7,40 (2H, m), 6.87 in (1H, d, J=8,4 Hz), 4,71 (2H, s), of 4.13 (4H, q, J=6.9 Hz), 1,47 (6H, t, J=6.9 Hz).

Example 256

0.27 g of [2-(3,4-dioxyphenyl)oxazol-4-yl]methylamine obtained in reference example 37, and 0.3 ml of triethylamine were dissolved in 10 ml of acetonitrile. To the mixture was added to 0.19 g o-toluensulfonate and the mixture premesis is whether at room temperature for 1 hour. To the reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer twice washed with water and the solvent was removed. The obtained residue was purified using a column with silica gel (n-hexane:ethyl acetate = 1:1). The crude crystals are recrystallized from a mixture of n-hexane and ethyl acetate to obtain 0.3 g of white powdery N-[2-(3,4-dioxyphenyl)oxazol-4-ylmethyl]-2-methylbenzenesulfonamide.

1H-NMR (CDCl3) δ: of 7.96 (1H, DD, J=7,5, 1.5 Hz), of 7.48-7,16 (6H, m), 6.90 to (1H, d, J=8,4 Hz), 5,11 (1H, users), 4,21-4,11 (6H, m)of 2.64 (3H, s), 1,52 of 1.46 (6H, m).

Example 257

0.5 g of 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-she obtained in example 102, and 0.18 ml of hydrazinoacetate were added to diethylene glycol. To the mixture was added 0.14 g of potassium hydroxide and the mixture was stirred at 150°C for 1 hour. The reaction mixture was allowed to cool, then to the mixture was added water and was carried out by extraction with ethyl acetate. Was carried out by drying using anhydrous magnesium sulfate and the solvent was removed. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 4:1) to give 0.1 g of colorless, oily 2-(3-cyclopropylmethoxy-4-methoxyphenyl)-4-[3-(2-ethoxyphenyl)propyl]oxazole.

1H-NMR (CDCl3) δ: 7,58 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,39 (1H, s), 7,17 for 7.12 (2H, m), 6,93-for 6.81 (3H, m, a 4.03 (2H, q, J=6.9 Hz), 3,94-to 3.92 (5H, m), of 2.72 (2H, t, J=7.5 Hz), 2,62 (2H, t, J=7.5 Hz), 2,03 is 1.96 (2H, m), USD 1.43-1,25 (4H, m), is 0.69 to 0.63 (2H, m), and 0.40 and 0.35 (2H, m).

Example 258

1.6 g of sodium hydride suspended in 100 ml of tetrahydrofuran. To the mixture while cooling with ice and stirring was sequentially added of 2.68 g of 1-(2-were)ethanone and to 6.58 g of 2-(3-benzyloxy-4-methoxyphenyl)-4-chlorothioxanthone obtained in reference example 5, and the mixture was heated and boiled under reflux for 4 hours. To the mixture was added saturated aqueous solution of ammonium chloride under ice cooling. After stirring for 15 minutes, to the mixture was added water and was carried out by extraction with ethyl acetate. Then was carried out by drying using anhydrous magnesium sulfate and the solvent was removed. The residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 4:1) and 1.6 g of the obtained crude product was dissolved in 20 ml of ethanol. To the mixture was added 0.16 g of 10% palladium-on-carbon in powder form and the mixture is stirred in hydrogen atmosphere for 18 hours. The reaction mixture was filtered and the obtained filtrate was concentrated. The residue was purified column chromatography on silica gel (dichloromethane:ethanol = 100:1) obtaining of 0.47 g of yellow oily 2-(3-hydroxy-4-methoxyphenyl)-4-(3-o-tolylpropan)oxazole.

1H-NMR (CDCl3) δ: 7,60-rate of 7.54 (2H, m), 7,38 (1H, s), 7,15-was 7.08 (4H, m), 6.90 to (1H, d, J=8.4 and the C), the 5.65 (1H, s), of 3.94 (3H, s), 2,72-2,62 (4H, m), is 2.37 (3H, s).

Example 259

With the use of 0.47 g of 2-(3-hydroxy-4-methoxyphenyl)-4-(3-o-tolylpropan)oxazole obtained in example 258, and 0.37 g of colorless, oily 2-(3-cyclopropylmethoxy-4-methoxyphenyl)-4-(3-o-tolylpropan)oxazole was obtained in the same manner as in example 111.

1H-NMR (CDCl3) δ: 7,58 (1H, DD, J=8,1, 2,1 Hz), 7,51 (1H, d, J=2.1 Hz), 7,38 (1H, s), 7,15-was 7.08 (4H, m), 6,92 (1H, d, J=8.1 Hz), 3,94-to 3.92 (5H, m), 2,72-2,62 (4H, m), 2,31 (3H, s), 2,04-of 1.92 (2H, m), of 1.40 and 1.35 (1H, m), 0,69 to 0.63 (2H, m), and 0.40 and 0.35 (2H, m).

Example 260

0.21 g of 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-she obtained in example 102 was added to 5 ml of ethanol and the mixture was stirred under ice cooling. To the mixture was gradually added 37 mg of sodium borohydride. After the temperature of the reaction mixture reached room temperature, was carried out by stirring for 2 hours. To the reaction mixture was added 5N. an aqueous solution of hydrochloric acid and the solvent is then removed. Was carried out by extraction with dichloromethane and the extract was washed with saturated saline solution. The extract is then dried over anhydrous magnesium sulfate, the solvent was removed and the residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1) to give 0.18 g of colorless, oily 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)PR is pan-1-ol.

1H-NMR (CDCl3) δ: 7,58 (1H, DD, J=8,4, and 2.1 Hz), to 7.50 (1H, d, J=1,8 Hz), 7,39-to 7.35 (2H, m), 7.23 percent-to 7.18 (1H, m), 6,97-6,84 (3H, m)5,00 (1H, users), 4,07 (2H, q, J=6.6 Hz), 3,94-to 3.92 (5H, m), 3,44 (1H, users), 2,80-2,60 (2H, m), 2,20-of 2.15 (2H, m), USD 1.43 to 1.37 (4H, m), is 0.69 to 0.63 (2H, m), 0,40-0,37 (2H, m).

Example 261

80 mg of 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-she obtained in example 139 was dissolved in 3 ml of dimethylformamide. To the mixture was added 0.2 g of sodium hydride under ice cooling and stirring and the mixture was stirred for 30 minutes. To the mixture was added 75 mg under the conditions and the reaction mixture was stirred at room temperature for 8 hours. To the reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer twice washed with water and the solvent was removed. The obtained residue was purified using a column with silica gel (n-hexane:ethyl acetate = 3:1) to give 35 mg of colorless, oily 3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]-2,2-dimethyl-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: to 8.41 (1H, DD, J=4,5, 1.2 Hz), 7,38-of 7.60 (3H, m), 7,34 (1H, s), 7,21-7,24 (1H, m), 6.90 to (1H, d, J=8.7 Hz), 4,63 (1H, Sept., J=6.0 Hz), of 3.94 (3H, s)and 3.15 (2H, s), of 2.28 (3H, s), 1,38-1,49 (12H, m).

Example 262

Using 0.9 g of methyl 3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}propionate obtained in reference example 83, of 1.05 g of a yellow oily methyl 3-(3-methoxypyridine-2-yl)-2-{2-[4-m is toxi-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-3-oxopropionate was obtained in the same way, as in example 100.

1H-NMR (CDCl3) δ: of 8.25 (1H, DD, J=4,5, 1.5 Hz), the 7.65 (1H, DD, J=8,4, and 2.1 Hz), 7,55 (1H, d, J=2.1 Hz), 7,47-7,33 (3H, m)6,94 (1H, d, J=8,4 Hz)to 5.17 (1H, t, J=6.9 Hz), 4,43 (2H, q, J=8,4 Hz), 3,93 (3H, s)to 3.92 (3H, ), the 3.65 (3H, s), 3,32 is 3.23 (2H, m).

Example 263

Using 0.7 g of methyl 3-(3-methoxypyridine-2-yl)-2-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-3-oxopropionate obtained in example 262, 0,42 g of colorless, oily methyl 2-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-methyl-3-(3-methylpyridin-2-yl)-3-oxopropionate was obtained in the same manner as in example 261.

1H-NMR (CDCl3) δ: 8,18 (1H, DD, J=6,9, 1.8 Hz), to 7.64 (1H, DD, J=8,4, and 2.1 Hz), 7,54 (1H, d, J=2.1 Hz), 7,42-7,34 (3H, m), 6,93 (1H, d, J=8.7 Hz), 4,43 (2H, q, J=8,4 Hz), 3,93 (3H, s), 3,91 (3H, s)to 3.64 (3H, s), 3,40 (1H, d, J=15 Hz), 3,26 (1H, d, J=15 Hz).

Example 264

With the use of 0.42 g of methyl 2-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-methyl-3-(3-methylpyridin-2-yl)-3-oxopropionate obtained in example 263, 0.25 g of colorless oily 1-(3-methoxypyridine-2-yl)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-2-methylpropan-1-she's got in the same way as in example 136.

1H-NMR (CDCl3) δ: 8,24 (1H, DD, J=4,5, 1.5 Hz), to 7.67 (1H, DD, J=8,4, and 2.1 Hz), EUR 7.57 (1H, d, J=2.1 Hz), 7,43-7,28 (3H, m)6,94 (1H, d, J=8.7 Hz), of 4.45 (1H, q, J=8,4 Hz), is 4.21 (1H, q, J=6.9 Hz), 3,91 (3H, s), 3,88 (3H, ), 3,15-of 3.06 (1H, m), 2,73-of 2.64 (1H, m)of 1.23 (3H, d, J=7,2 Hz).

Example 265

Using 0.2 g of 1-(3-methoxypyridine-2-yl)--{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-2-methylpropan-1-it, obtained in example 264, 80 mg of colorless oily 1-(3-methoxypyridine-2-yl)-3-{2-[4-methoxy-3-(2,2,2-triptoreline)phenyl]oxazol-4-yl}-2,2-DIMETHYLPROPANE-1-she's got the same method as in example 261.

1H-NMR (CDCl3) δ: 8,17 (1H, DD, J=4,5, 1.5 Hz), of 7.70 (1H, DD, J=8,4, 1.8 Hz), 7,60 (1H, d, J=1,8 Hz), 7,31-7,21 (2H, m), of 6.96 (1H, d, J=8,4 Hz), of 4.45 (2H, q, J=8,4 Hz)to 3.92 (3H, s), of 3.78 (3H, s), 3,05 (2H, s)of 1.34 (6H with).

Example 266

60 ml triperoxonane acid was stirred under ice cooling was added 12.3 g of the compound obtained in example 231, and was carried out by stirring for one hour. Upon completion of the reaction, the reaction mixture was neutralized by adding saturated aqueous sodium bicarbonate solution and the resulting mixture was added ethyl acetate. The organic layer was twice washed with water, separated, concentrated under reduced pressure and the obtained crude crystals are recrystallized from ethanol to obtain, thus, 5.9 g of white powdery 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-hydroxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: 12,2 (1H, s), 7,81 (1H, d, J=8.1 Hz), 7,62-7,26 (9H, m), 6,99-6,85 (3H, m), 5,19 (2H, s)to 3.92 (3H, s), of 3.43 (2H, t, J=7.5 Hz), to 3.02 (2H, t, J=7.5 Hz).

Example 267

Using the compound obtained in example 266, and Chlorodifluoromethane white powdery 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-deformational)propane-1-nolocal, following the procedure of example 19.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), of 7.90-6,60 (7H, m), 6,34 (1H, t, J=73,8 Hz), 5,20 (2H, s)to 3.92 (3H, s)to 3.36 (2H, t, J=7.2 Hz), to 2.29 (2H, t, J=7.2 Hz).

Reference example 84

Using 2-ftramadol colorless, oily 2-foretelltarot was obtained by following the procedure described in reference example 50.

1H-NMR (CDCl3) δ: 4,76-to 4.73 (1H, m), 4,60-4,58 (1H, m), 4.53-in-4,50 (1H, m), 4,43-to 4.41 (1H, m), is 3.08 (3H, s).

Reference example 85

Using 2,2-deperately colorless oily 2,2-deflorationshane was obtained by following the procedure described in reference example 50.

1H-NMR (CDCl3) δ: 6,01 (1H, TT, J=54,3, 3,9 Hz), to 4.38 (2H, TD, J=12,9, 3,9 Hz), of 3.12 (3H, s).

Example 268

Using the compound obtained in example 266, and the compound obtained in reference example 84, white powdery 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-[2-(2-floratone)phenyl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.8 Hz), to 7.61-to 7.59 (2H, m), 7,49-7,31 (7H, m), 7,07 (1H, t, J=7.8 Hz), 6,92 (2H, d, J=8.7 Hz), 5,20 (2H, s), 4,90-to 4.87 (1H, m), 4,74-4,71 (1H, m), 4,37 is 4.35 (1H, m), 4,28-4.26 deaths (1H, m,), to 3.92 (3H, s), 3,44 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz).

Example 269

Using the compound obtained in example 266, and the compound obtained in reference example 85, white powdery 3-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-yl]-1-[2-(2,2-diflorasone)f the Nile]propane-1-he got following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.8 Hz), to 7.61-7,28 (9H, m), was 7.08 (1H, t, J=7.8 Hz), 6,95-6,89 (2H, m), from 6.22 (1H, TT, J=54,9, 3,9 Hz), 5,19 (2H, s), the 4.29 (1H, dt, J=12,9, 3,9 Hz)to 3.92 (3H, s)to 3.38 (2H, t, J=7.5 Hz), 2,98 (2H, t, J=7.5 Hz).

Example 270

Using the compound obtained in example 267, white powdery 1-(2-deformational)-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 2.

1H-NMR (CDCl3) δ: 7,71 (1H, t, J=7.5 Hz), 7,54-7,41 (4H, m), 7,38-7,16 (2H, m), 6.89 in (1H, d, J=8.1 Hz), 6,59 (1H, t, J=74,7 Hz), 5,69 (1H, s), 3,93 (3H, s)to 3.36 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz).

Example 271

Using the compound obtained in example 268, white powder of 1-[2-(2-floratone)phenyl]-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 2.

1H-NMR (CDCl3) δ: 7,73 (1H, DD, J=7,8, 1.8 Hz), 7,55-7,42 (4H, m), 7,05 (1H, t, J=7.8 Hz), 6,91 (2H, d, J=8.7 Hz), 4,91-4,88 (1H, m), 4.75 V-4,72 (1H, m), of 4.38 is 4.35 (1H, m), the 4.29-4.26 deaths (1H, m), of 3.94 (3H, s), of 3.43 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz).

Example 272

Using the compound obtained in example 269, white powder of 1-[2-(2,2-diflorasone)phenyl]-3-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 2.

1H-NMR (CDCl3) δ: 7,73 (1H, DD, J=7,8, 1.8 Hz), 7,56-7,41 (4H, m), was 7.08 (1H, t, J=7.8 Hz), 6,92-6,87 (2H, m), 6,21 (1H, TT, J=54,9, 3,9 Hz), 5,67 (1H, s), the 4.29 (1H, dt, J=12,9, 3,9 Hz), of 3.94 (3H, s)to 3.38 (2H, t, J=7,2 Hz), 2,98 (2H, t, J=7.2 Hz).

Example 273

Using the compound obtained in example 270, and 2-bromopropane white powdery 1-(2-deformational)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,70-of 7.25 (5H, m), 7,20-to 6.80 (2H, m), 6,59 (1H, t, J=73,5 Hz), with 4.64 (1H, m), 3,93 (3H, s)of 1.39 (3H, d, J=6.0 Hz).

Example 274

Using the compound obtained in example 270, and ethyliodide white powdery 1-(2-deformational)-3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), 7,60-7,46 (3H, m), 7,42 (1H, s), 7,31-7,16 (2H, m)6,91 (1H, d, J=8.1 Hz), 6,59 (1H, t, J=73,5 Hz), 4,18 (2H, q, J=7.2 Hz), to 3.92 (3H, s), 3,37 (2H, t, J=7,2 Hz)of 3.00 (2H,, t, J=7.2 Hz), for 1.49 (3H, t, J=7.2 Hz).

Example 275

Using the compound obtained in example 271 and 2-bromopropane white powdery 1-(2-toreconsider)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,73 (1H, d, J=7,2 Hz), 7,58-rate of 7.54 (2H, m), 7,45-7,41 (2H, m),? 7.04 baby mortality (1H, t, J=7.2 Hz), 6,92 (2H, t, J=8.1 Hz), to 4.81 (2H, dt, J=47,4 and 4.2 Hz), with 4.64-4,60 (1H, m), 4,32 (2H, dt, J=23,1, 4,2 Hz)to 3.89 (3H, s), of 3.43 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), of 1.39 (6H, d, J=5.7 Hz).

Example 276

Using the compound obtained in example 271 and 4-bromo-1-butene white powdery 3-[2-(3-but-3-enyloxy-4-methoxyphenyl)oxazol-4-yl]-1-[2-(2-floratone)phenyl]about the an-1 is received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,73 (1H, d, J=7.5 Hz), 7,58-7,53 (2H, m), 7,45-7,42 (2H, m), 7,03 (1H, t, J=7.8 Hz), 6,92 (2H, t, J=8,4 Hz), 6,00 of 5.84 (1H, m), to 5.21-5,09 (2H, m), to 4.81 (2H, dt, J=47,4 and 4.2 Hz), 4,32 (2H, dt, J=23,1, 4,2 Hz), 4,14 (2H, t, J=7.2 Hz), 3,90 (3H, s), of 3.43 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), 2,64-2,61 (2H, m).

Example 277

Using the compound obtained in example 271 and isobutyl bromide is a white powder of 1-[2-(2-floratone)phenyl]-3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,73 (1H, DD, J=7,8, 1.8 Hz), EUR 7.57-7,51 (2H, m), of 7.48-7,42 (2H, m), 7,40 (1H, t, J=7.5 Hz), 6,92 (2H, t, J=8.7 Hz), to 4.81 (2H, dt, J=47,4 and 4.2 Hz), 4,32 (2H, dt, J=23,1, 4,2 Hz), 3,90 (3H, s), a-3.84 (2H, d, J=6.9 Hz), of 3.43 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), 2,23 with 2.14 (1H, m), was 1.04 (6H, d, J=5.7 Hz).

Example 278

Using the compound obtained in example 272, and 2-bromopropane white powder of 1-[2-(2,2-diflorasone)phenyl]-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,5, 1.8 Hz), to 7.59-7,44 (3H, m), 7,41 (1H, s), was 7.08 (1H, t, J=7.5 Hz), 6,91 (1H, d, J=8,4 Hz), to 6.22 (1H, TT, J=54,6, 3,9 Hz)and 4.65 (1H, Sept., J=6.0 Hz), the 4.29 (2H, TD, J=12,9, 3,9 Hz), 3,90 (3H, s)to 3.38 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), of 1.40 (6H, d, J=6.0 Hz).

Example 279

Using the compound obtained in example 272, and 1-bromopropane white powder of 1-[2-(2,2-diflorasone)phenyl]-3-[2-(3-propoxy-4-methoxyphenyl)oxazol-4-yl]prop is n-1 is received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.8 Hz), to 7.61-the 7.43 (3H, m), 7,41 (1H, s), was 7.08 (1H, t, J=7.5 Hz), 6,92-6,89 (2H, m), 6,23 (1H, TT, J=54,6, 3,9 Hz), the 4.29 (2H, TD, J=12,9, 3,9 Hz)4,06 (2H, t, J=6.9 Hz), 3,91 (3H, s), to 3.38 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), 1,90 (2H, cut, J=7,2 Hz), of 1.06 (3H, t, J=7.2 Hz).

Example 280

Using the compound obtained in example 272, and ethyliodide white powder of 1-[2-(2,2-diflorasone)phenyl]-3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.8 Hz), to 7.61-7,44 (3H, m), 7,41 (1H, s), was 7.08 (1H, t, J=7.8 Hz), 6,93-of 6.90 (2H, m), 6,23 (1H, TT, J=54,6, 3,9 Hz), the 4.29 (2H, TD, J=12,9, 3,9 Hz), 4,18 (2H, q, J=6.9 Hz), to 3.92 (3H, s), to 3.38 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), 1,50 (3H, t, J=6.9 Hz).

Example 281

Using the compound obtained in example 272, and allylbromide white powdery 3-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-yl]-1-[2-(2,2-diflorasone)phenyl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.8 Hz), 7,60-7,44 (3H, m), 7,41 (1H, s), was 7.08 (1H, t, J=7.5 Hz), 6,94-6,89 (2H, m), 6,41-6,04 (2H, m), 5,44 (1H, DD, J=17.4 years, 1.5 Hz), 5,31 (1H, DD, J=10,2, 1.5 Hz), the 4.29 (2H, TD, J=12,9, 3,9 Hz)to 3.92 (3H, s)to 3.38 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz).

Example 282

Using the compound obtained in example 272, and 4-bromo-1-butene white powdery 3-[2-(3-but-3-enyloxy-4-methoxyphenyl)oxazol-4-yl]-1-[2-(2,2-diflorasone)phenyl]propane-1-he received following procedure is e of example 3.

1H-NMR (CDCl3) δ: of 7.75 (1H, DD, J=7,8, 1.8 Hz), 7,60-7,44 (3H, m), 7,42 (1H, s), to 7.09 (1H, t, J=7.5 Hz), 6,93-6,89 (2H, m), 6,23 (1H, TT, J=54,6, 3,9 Hz), 5,99-to 5.85 (1H, m), 5,23-5,10 (2H, m), the 4.29 (2H, TD, J=12,9, a 3.9 Hz), to 4.14 (2H, t, J=7.2 Hz), 3,91 (3H, s), 3,39 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), 2,68-2,60 (2H, m).

Example 283

Using the compound obtained in example 272, and (methyl bromide)cyclopropane white powdery 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-[2-(2,2-diflorasone)phenyl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: of 7.75 (1H, DD, J=7,8, 1.8 Hz), 7,58-7,44 (3H, m), 7,41 (1H, s), to 7.09 (1H, t, J=7.5 Hz), 6,93-of 6.90 (2H, m), 6,24 (1H, TT, J=54,6, 3,9 Hz), the 4.29 (2H, TD, J=12,9, 3,9 Hz), 3,94-3,91 (5H, m), 3,39 (2H, t, J=7,2 Hz), 2,99 (2H, t, J=7.2 Hz), USD 1.43 and 1.33 (1H, m), 0.70 to 0,63 (2H, m), 0,41-0,35 (2H, m).

Example 284

Using the compound obtained in example 272, and the compound obtained in reference example 85, white powdery 3-{2-[3-(2,2-diflorasone)-4-methoxyphenyl]oxazol-4-yl}-1-[2-(2,2-diflorasone)phenyl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.8 Hz), the 7.65 (1H, DD, J=7,8, 1.8 Hz), to 7.50 (1H, d, J=2.1 Hz), 7,50-7,42 (1H, m), 7,42 (1H, s), was 7.08 (1H, t, J=7.5 Hz), of 6.96-6.89 in (2H, m), 6.42 per-5,95 (2H, m), 4,35-to 4.23 (4H, m), 3,92 (3H, s), 3,39 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz).

Example 285

Using the compound obtained in example 272, and isobutyramide white powder of 1-[2-(2,2-diflorasone)phenyl]-3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]disappear to is-1 is received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, d, J=7.5 Hz), EUR 7.57-7,44 (3H, m), 7,41 (1H, s), was 7.08 (1H, t, J=7.5 Hz), 6,92-6,89 (2H, m), 6,23 (1H, TT, J=54,6, 3,9 Hz), the 4.29 (2H, TD, J=12,9, 3,9 Hz), 3,90 (3H, s), 3,85 (2H, d, J=6.6 Hz), 3,38 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), 2,19 (1H, cut, J=6.6 Hz), of 1.05 (6H, d, J=6,6 Hz).

Example 286

Using the compound obtained in reference example 35, compound obtained in reference example 70, pale yellow oily 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-methoxyethoxymethyl)propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: 7,66 (1H, DD, J=7,8, 1.8 Hz), 7,56-7,38 (3H, m), 7,17 (1H, d, J=8,4 Hz),? 7.04 baby mortality (1H, t, J=7.5 Hz), 6,92-to 6.88 (2H, m), of 5.26 (2H, s), 4,21-4,08 (4H, m), 3,49 (3H, s), 3,40 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7,2 Hz), 1,51-of 1.45 (6H, m).

Example 287

Using the compound obtained in example 286, white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-hydroxyphenyl)propane-1-received, following the procedure of example 266.

1H-NMR (CDCl3) δ: 12,25 (1H, s), 7,82 (1H, DD, J=8,1, 1.5 Hz), 7,60-the 7.43 (4H, m), 6,98 (1H, d, J=8,4 Hz), 6,92-6,86 (2H, m), 4,21-4,10 (4H, m), 3,44 (2H, t, J=7.2 Hz), 3,03 (2H, t, J=7.2 Hz), 1,51 was 1.43 (6H, m).

Example 288

Using the compound obtained in example 287, and Chlorodifluoromethane white powdery 3-[2-(3,4-detoxification-4-yl)-1-(2-deformational)propane-1-received, following the procedure of example 19.

1H-NMR (CDCl3) δ: 7,51 (1H, d, J=8.7 Hz), 7,60 was 7.45 (3H, m), 7,30 (1H, s), 7,28-7,19 (2H, m)6,0 (1H, d, J=8.7 Hz), to 6.58 (1H, t, J=75 Hz)to 4.15 (4H, q, J=7.2 Hz) to 3.36 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 1,47 (6H, t, J=7.2 Hz).

Example 289

Using the compound obtained in example 287, and the compound obtained in reference example 84, white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-[2-(2-floratone)phenyl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.8 Hz), 7,56-7,41 (4H, m),? 7.04 baby mortality (1H, TD, J=7,5, and 0.9 Hz), 6,95-to 6.88 (2H, m), to 4.81 (2H, dt, J=47,1, 4,2 Hz), 4,32 (2H, dt, J=27,3, 4,2 Hz), 4,21-4,10 (4H, m), of 3.43 (2H, t, J=7.2 Hz), 3.00 for (2H, t, J=7.2 Hz), 1,50-of 1.45 (6H, m).

Example 290

Using the compound obtained in example 287, and the compound obtained in reference example 85, white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-[2-(2,2-diflorasone)phenyl]propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,5, 1.8 Hz), 7,56-the 7.43 (3H, m), 7,41 (1H, s), was 7.08 (1H, t, J=7.5 Hz), make 6.90 (1H, d, J=7.8 Hz), 6,23 (1H, TT, J=54,9, 3,9 Hz), the 4.29 (2H, TD, J=13,2, 3,9 Hz), 4,21-4,10 (4H, m)to 3.38 (2H, t, J=7.5 Hz), 2,98 (2H, t, J=7.5 Hz), 1,50-of 1.45 (6H, m).

Example 291

0.2 g of the compound obtained in example 223, and 0.1 ml of triethylamine were dissolved in 5 ml of dichloromethane, the resulting solution was added 0.1 ml of acetylchloride and the mixture was stirred for 6 hours at room temperature. Upon completion of the reaction, to the reaction mixture were added water and the resulting mixture was extracted with ethyl acetate. The organic layer twice item is washed with water and the solvent drove by distillation. The residue was purified using a column with silica gel (n-hexane:ethyl acetate = 2:1) and the crude crystals are recrystallized from ethanol to obtain, thus, 15 mg of white powdery 2-{3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propionyl}phenylacetate.

1H-NMR (CDCl3) δ: 7,83 (1H, DD, J=7,8, 1.5 Hz), 7,60 is 7.50 (3H, m), 7,42 (1H, s), 7,34-7,28 (1H, m), 7,12 (1H, DD, J=8,1, 0.9 Hz), 6,92 (1H, d, J=8,4 Hz), 4,69-br4.61 (1H, m), 3,90 (3H, s), of 3.32 (2H, t, J=7.2 Hz), 2,97 (2H, t, J=7.2 Hz), to 2.35 (3H, s)of 1.40 (6H, d, J=6.0 Hz).

Example 292

Using the compound obtained in reference example 35, 1-(2-trifloromethyl)ethanone white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-trifloromethyl)propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), 7,58-7,41 (3H, m), 7,38 (1H, s), 7,35-7,29 (2H, m), 6.90 to (1H, d, J=8,4 Hz), 4,20-4,10 (4H, m)to 3.34 (2H, t, J=6,9 Hz)of 3.00 (2H, t, J=6.9 Hz), to 1.48 (6H, t, J=6.9 Hz).

Example 293

Using the compound obtained in reference example 11, and 1-(2-trifloromethyl)ethanone white powdery 3-[2-(3-cyclopropylmethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(2-trifloromethyl)propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: of 7.70 (1H, d, J=8.7 Hz), EUR 7.57-7,53 (3H, m), 7,49 (1H, s), 7,42-7,30 (2H, m), 6.90 to (1H, d, J=8.7 Hz), 3,94-3,91 (5H, m)to 3.34 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 1,42-of 1.30 (1H, m), 0.67 and-of 0.64 (2H, m)0,40-0,36 (2H, m).

Using with the organisations, obtained in reference example 35, and the corresponding derivatives of acetophenone was obtained compounds of examples 294-299, following the procedure of example 190.

Example 294

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2,5-acid)propane-1-he

White powder

1H-NMR (CDCl3) δ: EUR 7.57-7,52 (2H, m), 7,40 (1H, s), 7,01 (1H, DD, J=9,0, 3,3 Hz), 6,90 (2H, t, J=8,4 Hz), 4,20-4,10 (4H, m), 3,85 (3H, s), of 3.78 (3H, s), 3,39 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), 1,47 (6H, t, J=6,9 Hz).

Example 295

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-ethoxy-5-were)propane-1-he

White powder

1H-NMR (CDCl3) δ: to 7.61-7,49 (3H, m), 7,40 (1H, s), 7,25-7,20 (2H, m), 6.90 to (1H, d, J=8.1 Hz), 6,83 (1H, d, J=8,4 Hz), 4,21-4,06 (6H, m)to 3.41 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), 2,28 (3H, s), 1,53-of 1.40 (9H, m).

Example 296

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2,4-dimetilfenil)propane-1-he

Colorless powder

1H-NMR (CDCl3) δ: 7,63 (1H, d, J=8,4 Hz), 7,54 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,42 (1H, s), 7,06-7,02 (2H, m), 6.90 to (1H, d, J=8,4 Hz)to 4.17 (2H, q, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), 3,30 (2H, t, J=7,2 Hz), 2,99 (2H, t, J=7.2 Hz), 2.49 USD (3H, s), of 2.34 (3H, s)to 1.48 (6H, t, J=6.9 Hz).

Example 297

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2,5-dimetilfenil)propane-1-he

Colorless needle crystals

1H-NMR (CDCl3) δ: at 7.55 (1H, ushers, J=8.7 Hz), 7,52 (1H, users), 7,44 (1H, userd, J=8.7 Hz), 7,17-to 7.09 (2H, m), 6.90 to (1H, d, J=8.7 Hz), 4,17 (2H, q, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), 3,29 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7,2 Hz), 2,44 (3H, s), of 2.33 (3H, s)of 1.47 (6H, t, J=6.9 Hz).

Example 298

3-[2-(3,4-diethoxy the Nile)oxazol-4-yl]-1-(2-ethoxy-4-were)propane-1-he

White powder

1H-NMR (CDCl3) δ: 7,66 (1H, d, J=7.8 Hz), 7,60-7,51 (2H, m), 7,39 (1H, s), make 6.90 (1H, d, J=8,4 Hz), 6,79 (1H, d, J=8,4 Hz), was 6.73 (1H, s), 4,21-4,08 (6H, m), 3,40 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), a 2.36 (3H, ), 1,53-of 1.45 (9H, m).

Example 299

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-ethoxy-4-forfinal)propane-1-he

Colorless needle crystals

1H-NMR (CDCl3) δ: for 7.78 (1H, DD, J=8,7, 7,2 Hz), 7,54 (1H, DD, J=8,4, and 2.1 Hz), 7,51 (1H, d, J=2.1 Hz), 7,39 (1H, users), of 6.90 (1H, d, J=8,4 Hz), of 6.71-of 6.61 (2H, m)to 4.16 (2H, q, J=6.9 Hz), 4,14 (2H, q, J=6.9 Hz), 4,11 (2H, kV, J=6.9 Hz), 3,39 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), for 1.49 (3H, t, J=6.9 Hz), 1,47 (6H, t, J=6.9 Hz).

Example 300

Used the compound obtained in reference example 54, and methyl (2-methoxymethyl)benzoate and treated by following the procedure of example 100, with subsequent processing in accordance with a reference example 48 to obtain white powdery 3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-methoxymethyl)propane-1-it.

1H-NMR (CDCl3) δ: 7,74 (1H, DD, J=7,8, 1.2 Hz), of 7.64-7,27 (6H, m)6,91 (1H, d, J=8,4 Hz), to 4.73 (2H, s), 4,21-4,10 (4H, m), 3.43 points (3H, s)to 3.34 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 1,51 was 1.43 (6H, m).

Using the compound obtained in reference example 54, and the corresponding methylbenzoate derivatives were obtained compounds of examples 301-303, following the procedure of example 300.

Example 301

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-ethylphenyl)propane-1-he

1H-NMR (CDCl3) δ: 7,62-7,51 (4H, m), the 7.43 (1H, s), 7,38-7,30 (2H, m), 90 (1H, d, J=8.7 Hz), 4,18 is 4.13 (4H, m), and 3.31 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), of 2.81 (2H, q, J=7.5 Hz), to 1.48 (6H, t, J=6.9 Hz), of 1.20 (3H, t, J=7.5 Hz).

Example 302

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2,3-acid)propane-1-he

1H-NMR (CDCl3) δ: 7,56-7,51 (2H, m), 7,41 (1H, s), 7.18 in-7,01 (3H, m), 6.90 to (1H, d, J=8,4 Hz), 4,21-4,10 (4H, m)to 3.89 (6H, s)to 3.38 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), to 1.48 (6H, t, J=6.9 Hz).

Example 303

3-[2-(3,4-dioxyphenyl)oxazol-4-yl]-1-(2-ethoxy-3-were)propane-1-he

1H-NMR (CDCl3) δ: 7,55-7,51 (2H, m), 7,40 (1H, s), of 7.36-7.29 trend (2H, m),? 7.04 baby mortality (1H, t, J=7.2 Hz), make 6.90 (1H, d, J=8.1 Hz), 4,20-4,11 (4H, m), 3,83 (2H, q, J=7.5 Hz), 3,39 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), 2,30 (3H with), to 1.48 (6H, t, J=6.9 Hz), of 1.26 (3H, t, J=6.9 Hz).

Example 304

Using the compound obtained in reference example 58, and 1-(2-ethoxy-4-forfinal)ethanone pale yellow powder of 1-(2-ethoxy-4-forfinal)-3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: to 7.77 (1H, t, J=7.8 Hz), 7,56 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,40 (1H, s)6,91 (1H, d, J=8,4 Hz), of 6.71-of 6.61 (2H, m), 4,21-4,07 (4H, m)to 3.92 (3H, s), 3,39 (2H, t, J=7.2 Hz), 2,98 (2H,, t, J=7.2 Hz), 1,52 to 1.47 (6H, m).

Example 305

Using the compound obtained in reference example 58, and 1-(4-fluoro-2-isopropoxyphenyl)ethanone colorless, oily 3-[2-(3-ethoxy-4-methoxyphenyl)oxazol-4-yl]-1-(4-fluoro-2-isopropoxyphenyl)propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: to 7.77 (1H, t, J=7.8 for the TS) EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), 7,51 (1H, d, J=1,8 Hz), 7,40 (1H, s)6,91 (1H, d, J=8,4 Hz), of 6.71-of 6.61 (2H, m), 4,63 (1H, Sept., J=6.0 Hz), 4,18 (2H, q, J=6.9 Hz), to 3.92 (3H, s)to 3.38 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7.2 Hz), 1,50 (3H, t, J=6.9 Hz), of 1.42 (6H, d, J=6.0 Hz).

Example 306

Using the compound obtained in reference example 68, 1-(2-ethoxy-5-were)ethanone white powdery 1-(2-ethoxy-5-were)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: 7,60-7,40 (3H, m), 7,39 (1H, s), 7.24 to 7,19 (1H, m)6,91 (1H, d, J=8.1 Hz), 6,83 (1H, d, J=8,4 Hz), 4,69-4,58 (1H, m), 4,10 (2H, q, J=6.9 Hz), with 3.89 (3H, s)to 3.41 (2H, t, J=7.2 Hz), 2,98 (2H, t, J=7,2 Hz)to 2.29 (3H, s), 1,48-to 1.38 (9H, m).

Example 307

Using the compound obtained in reference example 68, 1-(2-ethoxy-4-were)ethanone white powdery 1-(2-ethoxy-4-were)-3-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-yl]propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: 7,66 (1H, d, J=8.1 Hz), to 7.59-7,53 (2H, m), 7,39 (1H, s)6,91 (1H, d, J=8,4 Hz), 6,79 (1H, d, J=8.1 Hz), 6.73 x (1H, s), 4,58-4,71 (1H, m), of 4.12 (2H, q, J=6.9 Hz), 3,90 (1H, s) 3,40 (2H, t, J=7.5 Hz), 2,98 (2H, t, J=7.5 Hz), a 2.36 (3H, s)to 1.48 (3H, t, J=6.9 Hz), of 1.40 (6H, d, J=6.0 Hz).

Example 308

Using the compound obtained in example 136, and Chlorodifluoromethane white powdery 3-[2-(3-deformedarse-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 4.

1H-NMR (CDCl3

Example 309

Using the compound obtained in example 136, and the compound obtained in reference example 85, white powdery 3-{2-[3-(2,2-diflorasone)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, and 0.9 Hz), 7,66 (1H, DD, J=8,4, and 2.1 Hz), 7,60-rate of 7.54 (2H, m), 7,46 (1H, s), 7,35-7,31 (1H, m)6,94 (1H, d, J=8.7 Hz), 6,16 (1H, TT, J=54,9, 1.2 Hz) 4,29 (2H, TD, J=12,9, 1.2 Hz), to 3.92 (3H, ), 3,61 (2H, t, J=6.9 Hz), a 3.01 (2H, t, J=6.9 Hz), 2,58 (3H, s).

Example 310

Using the compound obtained in example 136, and the compound obtained in reference example 84, white powdery 3-{2-[3-(2-floratone)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50-8,49 (1H, m), 7,63-rate of 7.54 (3H, m), 7,45 (1H, s), 7,34-7,27 (1H, m), 6,93 (1H, d, J=8.7 Hz), 4,88 (1H, t, J=4, 2 Hz), 4.72 in (1H, t, J=4,2 Hz) 4,39 (1H, t, J=4, 2 Hz), 4,30 (1H, t, J=4,2 Hz)to 3.92 (3H, C)of 3.60 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), to 2.57 (3H, s).

Example 311

Using the compound obtained in example 136, and 2-bromobutane yellow oily 3-[2-(3-sec-butoxy-4-methoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=45, 1.2 Hz), to 7.59-of 7.55 (3H, m), 7,54 (1H, s), 7,45-7,30 (1H, m)6,91 (1H, d, J=8,4 Hz), 4,43-4,37 (1H, m)to 3.89 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s), 1,86-of 1.62 (2H, m)of 1.34 (3H, d, J=6.6 Hz), and 1.00 (3H, t, J=6.6 Hz).

Example 312

Using the compound obtained in example 136, and 3-bromopentane white powdery 3-{2-[3-(1-ethylpropoxy)-4-methoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.61-7,53 (3H, m), 7,45 (1H, s), 7,34-7,30 (1H, m)6,91 (1H, d, J=8.1 Hz), 4,28-4,20 (1H, m)to 3.89 (3H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s), 1,78 by 1.68 (4H, m), and 0.98 (6H, t, J=6.6 Hz).

Example 313

Using the compound obtained in example 101, and Chlorodifluoromethane white powdery 3-[2-(3-deformedarse-4-methoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-received, following the procedure of example 4.

1H-NMR (CDCl3) δ: a 7.85-7,80 (2H, m), of 7.70 (1H, m), 7,50-7,40 (2H, m), 7,0-6,9 (3H, m), to 6.58 (1H, t, J=74,4 Hz), 4,14 (2H, q, J=6.9 Hz), 3,93 (3H, s), 3,42 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=6,9 Hz).

Example 314

Using the compound obtained in example 101, and the compound obtained in reference example 85, white powdery 3-{2-[3-(2,2-diflorasone)-4-methoxyphenyl]oxazol-4-yl}-1-(2-ethoxyphenyl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,73-7,63 (2H, m), 7,55 (1H, d, J=2.1 Hz), 7,46-7,39 (2H, m), 7,01-6,91 (3H, m), 6,16 (1H, TT, J=54,9, 1.2 Hz), the 4.29 (2H, TD, J=12,9, 1.2 Hz), 4,14 (2H, to the, J=6.9 Hz), 3,91 (3H, s), of 3.43 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), to 1.48 (3H, t, J=7.2 Hz).

Example 315

Using the compound obtained in example 101, and the compound obtained in reference example 84, white powdery 1-(2-ethoxyphenyl)-3-{2-[3-(2-floratone)-4-methoxyphenyl]oxazol-4-yl}propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: of 7.69 (1H, DD, J=7,8, 1.8 Hz), to 7.61 (1H, DD, J=8,4, 1.8 Hz), 7,55 (1H, s), 7,44-7,39 (2H, m), 7,00-6,91 (3H, m), to 4.81 (2H, dt, J=47,4 and 4.2 Hz), 4,32 (2H, dt, J=23,1, 4,2 Hz), 4,17-4,10 (2H, m), 3,90 (3H, s), to 3.41 (2H, t, J=7.2 Hz), 2,99 (2H, t, J=7.2 Hz), of 1.46 (3H, t, J=5.7 Hz).

Reference example 86

Using the compound obtained in reference example 59, and the compound obtained in reference example 85, white powdery ethyl 4-benzyloxy-3-(2,2-diflorasone)benzoate was obtained by following the procedure of example 4.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=8,4, and 2.1 Hz), to 7.61 (1H, d, J=2.1 Hz), 7,44-7,29 (5H, m), to 6.95 (1H, d, J=8,4 Hz), 6,11 (1H, TT, J=54,9 and 4.2 Hz), 5,19 (2H, s), to 4.38-is 4.21 (4H, m)of 1.39 (3H, t, J=7.2 Hz).

Reference example 87

Using the compound obtained in reference example 86, white powder 4-benzyloxy-3-(2,2-diflorasone)benzoic acid was obtained by following the procedure described in reference example 3.

1H-NMR (DMSO-d6) δ: to 7.61 (1H, DD, J=8,4, 1.8 Hz), 7,54 (1H, d, J=1,8 Hz), 7,50-7,30 (5H, m), 7,18 (1H, d, J=8,4 Hz), 6,38 (1H, TT, J=54,3, 3.6 Hz), with 5.22 (2H, s), 4,37 (2H, TD, J=14,7, 3.6 Hz).

Reference example 88

Using with the organisations, obtained in reference example 87, white powder 4-benzyloxy-3-(2,2-diflorasone)benzamide was obtained by following the procedure described in reference example 4.

1H-NMR (DMSO-d6) δ: 7,86 (1H, users), 7,56-7,29 (7H, m), 7,25 (1H, users), 7,14 (1H, d, J=8,4 Hz), 6,40 (1H, TT, J=54,3, 3.6 Hz), 5,20 (2H, s), 4,34 (2H, TD, J=14,7, 3.6 Hz).

Reference example 89

Using the compound obtained in reference example 88, a white powdery 2-[4-benzyloxy-3-(2,2-diflorasone)phenyl]-4-chlormethiazole was obtained by following the procedure described in reference example 5.

1H-NMR (CDCl3) δ: 7.68 per-of 7.60 (3H, m), 7,45-7,30 (5H, m), 7,01 (1H, d, J=8,4 Hz), 6,12 (1H, TT, J=54,9 and 4.2 Hz), is 5.18 (2H, s), 4,56 (2H, s), 4,30 (2H, TD, J=13,2, 4,2 Hz).

Reference example 90

Using the compound obtained in reference example 89, a white powdery dimethyl 2-{2-[4-benzyloxy-3-(2,2-diflorasone)phenyl]oxazol-4-ylmethyl}malonate was obtained by following the procedure described in reference example 47.

1H-NMR (CDCl3) δ: 7,63-EUR 7.57 (2H, m), 7,45-7,30 (6H, m), of 6.99 (1H, d, J=8.1 Hz), 6,12 (1H, TT, J=54,9 and 4.2 Hz), is 5.18 (2H, s), the 4.29 (2H, TD, J=13,2, 4,2 Hz)to 3.89 (2H, t, J=7.5 Hz), of 3.75 (6H, s)3,18 (2H, t, J=7.5 Hz).

Reference example 91

Using the compound obtained in reference example 90, brownish oily methyl 3-{2-[4-benzyloxy-3-(2,2-diflorasone)phenyl]oxazol-4-yl}propionate was obtained by following the procedure described in reference example 48.

1H-NMR (DCl 3) δ: of 7.64-to 7.59 (2H, m), 7,42-7,33 (6H, m), of 6.99 (1H, d, J=8.1 Hz), 6,12 (1H, TT, J=54,9 and 4.2 Hz), is 5.18 (2H, s), the 4.29 (2H, TD, J=13,2, 4,2 Hz), 3,68 (3H, s), only 2.91 (2H, t, J=7.5 Hz), of 2.72 (2H, t, J=7.5 Hz).

Example 316

Using the compound obtained in referential example 91, pale yellow oily methyl 2-{2-[4-benzyloxy-3-(2,2-diflorasone)phenyl]oxazol-4-ylmethyl}-3-(3-methylpyridin-2-yl)-3-oxopropionate was obtained by following the procedure of example 100.

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), 7,60-7,52 (3H, m), 7,46-7,30 (7H, m), 6,97 (1H, d, J=8.1 Hz), 6,11 (1H, TT, J=54,9 and 4.2 Hz), 5,24-5,16 (3H, m), 4,27 (2H, TD, J=13,2, 4,2 Hz), 3,66 (3H, s), 3,34-up 3.22 (2H, m)2,60 (3H, s).

Example 317

Using the compound obtained in example 316, white powdery 3-{2-[3-(2,2-diflorasone)-4-hydroxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 136.

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), to 7.61-EUR 7.57 (2H, m), 7,52 (1H, s), 7,45 (1H, s), 7,34-7,30 (1H, m), 7,00 (1H, d, J=8.1 Hz), 6,11 (1H, TT, J=54,9 and 4.2 Hz), 6,07 (1H, s), 4,32 (2H, TD, J=13,2, 4,2 Hz)and 3.59 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), to 2.57 (3H, s).

Example 318

Using the compound obtained in example 317, and under the conditions of white powdery 3-{2-[3-(2,2-diflorasone)-4-ethoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,51 (1H, d, J=4.5 Hz), 7,66-EUR 7.57 (3H, m), 7,46 (1H, s), 7,34-7,30 (1H, m)6,94 (1H, d, J=8,4 Hz), 6,14 (1H, TT, J=54,6, 3,9 Hz), 4,28 (2H, TD, J=12,9, 3,9 Hz), of 4.13 (2H, q, J=6.9 Hz), of 3.60 (2H, t, J7,5 Hz), to 3.02 (2H, t, J=7.5 Hz), to 2.57 (3H, s)of 1.47 (3H, t, J=6.9 Hz).

Example 319

Using the compound obtained in example 317, and 2-bromopropane white powdery 3-{2-[3-(2,2-diflorasone)-4-isopropoxyphenyl]oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,51 (1H, d, J=4.5 Hz), the 7.65 EUR 7.57 (3H, m), 7,46 (1H, s), 7,34-7,30 (1H, m), to 6.95 (1H, d, J=8,4 Hz), 6,12 (1H, TT, J=54,6, 3,9 Hz), 4,62-of 4.54 (1H, m), 4.26 deaths (2H, TD, J=12,9, 3,9 Hz), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s)to 1.37 (6H, d, J=6.0 Hz).

Example 320

Using the compound obtained in reference example 7 and 2-diplomatchisinau acid white powdery N-[2-(3-benzyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-deformational was obtained by following the procedure of example 1.

1H-NMR (CDCl3) δ: 8,10 (1H, DD, J=7,8, 1.8 Hz), of 7.64-EUR 7.57 (3H, m), 7,51 was 7.45 (4H, m), 7,40-7,26 (4H, m), to 7.15 (1H, d, J=8,4 Hz), to 6.95 (1H, d, J=9.0 Hz), 6,59 (1H, t, J=72,9 Hz), 5,20 (2H, s), br4.61 (2H, d, J=5.4 Hz), 3,93 (3H, s).

Example 321

Using the compound obtained in example 320, a white powdery 2-deformedarse-N-[2-(3-hydroxy-4-methoxyphenyl)oxazol-4-ylmethyl]benzamide was obtained by following the procedure of example 2.

1H-NMR (CDCl3) δ: of 8.09 (1H, d, J=7.8 Hz), of 7.64 was 7.45 (5H, m), 7,32 (1H, t, J=7.8 Hz), to 7.15 (1H, d, J=7.8 Hz), 6,91 (1H, d, J=8,4 Hz), 6,60 (1H, t, J=72,9 Hz), 5,77 (1H, s), br4.61 (2H, d, J=5,1 Hz), of 3.94 (3H, s).

Example 322

Using the compound obtained in example 321, and allylbromide Ely powdery N-[2-(3-allyloxy-4-methoxyphenyl)oxazol-4-ylmethyl]-2-deformational received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,10 (1H, d, J=7.8 Hz), of 7.64-7,30 (6H, m), to 7.15 (1H, d, J=8,4 Hz)6,94 (1H, d, J=8.1 Hz), is 6.61 (1H, t, J=75 Hz), 6,17-between 6.08 (1H, m), the 5.45 (1H, DD, J=17,1, 1.5 Hz), 5,32 (1H, DD, J=a 10.5, 1.5 Hz), 4,70 (2H,, t, J=5.4 Hz), to 4.62 (2H, t, J=5.4 Hz), 3,93 (3H, s).

Example 323

Using the compound obtained in example 321, and 2-bromopropane white powdery 2-deformedarse-N-[2-(3-isopropoxy-4-methoxyphenyl)oxazol-4-ylmethyl]benzamide was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,10 (1H, d, J=7.8 Hz), of 7.64-7,30 (6H, m), to 7.15 (1H, d, J=8,4 Hz)6,94 (1H, d, J=8.1 Hz), is 6.61 (1H, t, J=75 Hz), 4,70-br4.61 (5H, m), 3,91 (3H, s)of 1.39 (6H, d, J=6.0 Hz).

Example 324

Using the compound obtained in example 17 and 3-bromopentane white powdery N-{2-[3-(1-ethylpropoxy)-4-methoxyphenyl]oxazol-4-ylmethyl}-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, d, J=4.5 Hz), 7,63-of 7.55 (4H, m), 7,32-7,28 (1H, m), 6,92 (1H, d, J=8,4 Hz), 4,59 (2H, d, J=6.0 Hz), 4,28-4,20 (1H, m), 3,90 (3H, s), was 2.76 (3H, s), 1,82 by 1.68 (4H, m), 0,99 (6H, t, J=7.5 Hz).

Example 325

Using the compound obtained in example 2 and 3-bromopentane white powdery 2-ethoxy-N-{2-[3-(1-ethylpropoxy)-4-methoxyphenyl]oxazol-4-ylmethyl}benzamide was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,24 (1H, DD, J=8,1, 1.8 Hz), 7,62-7,56 (3H, m), 7,45-7,39 (1H, m), 7,07 (1H, t, J=8.1 Hz), of 6.96-6,91 (2H, m), 4,63 (2H, DD, J=5,4, and 0.9 Hz), 4.26 deaths-to 4.14 (3H, m), 90 (3H, C)1,79 was 1.69 (4H, m), for 1.49 (3H, t, J=7,2 Hz), and 1.00 (6H, t, J=7.2 Hz).

Reference example 92

Using the compound obtained in reference example 44, colorless oily dimethyl 2-[2-(3-benzyloxy-4-deformational)oxazol-4-ylmethyl]malonate was obtained by following the procedure described in reference example 47.

1H-NMR (CDCl3) δ: of 7.70 (1H, s), to 7.59 (1H, d, J=7.8 Hz), of 7.48-7,22 (6H, m), 6,62 (1H, t, J=74,7 Hz), to 5.21 (2H, s), 3,90 (1H, t, J=7.5 Hz), to 3.73 (6H, s), 3,20 (2H, t, J=7.5 Hz).

Reference example 93

Using the compound obtained in reference example 92, pale yellow oily methyl 3-[2-(3-benzyloxy-4-deformational)oxazol-4-yl]propionate was obtained by following the procedure described in reference example 48.

1H-NMR (CDCl3) δ: 7,71 (1H, d, J=1,8 Hz), of 7.48-7,31 (6H, m), 7,24 (1H, d, J=8,4 Hz), 6,62 (1H, t, J=74,7 Hz), to 5.21 (2H, s), 3,70 (3H, s), with 2.93 (2H, t, J=7.2 Hz), a 2.71 (2H, t, J=7.2 Hz).

Example 326

Using the compound obtained in reference example 93, colorless, oily methyl 2-[2-(3-benzyloxy-4-deformational)oxazol-4-ylmethyl]-3-(3-methylpyridin-2-yl)-3-oxopropionate was obtained by following the procedure of example 100.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,8, 1.2 Hz), to 7.67-7,30 (10H, m), 7,21 (1H, d, J=8,4 Hz), 6,60 (1H, t, J=74,7 Hz), is 5.18 (2H, s), 4,11 (1H, t, J=7.2 Hz), the 3.65 (3H, s), 3,45-3,20 (2H, m)2,60 (3H, s).

Example 327

Used the compound obtained in example 326, and was treated by following the procedure of example 125, with subsequent quenching is rigid in accordance with the procedure of example 2 to obtain white powdery 3-[2-(4-deformedarse-3-hydroxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.67 was 7.45 (4H, m), 7,33-7,30 (1H, m), 7,16 (1H, d, J=8.1 Hz), to 6.58 (1H, t, J=75 Hz), USD 5.76 (1H, s), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s).

Example 328

0,15 compound obtained in example 327, and 0.18 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 3 ml of ethanol, and then to the resulting solution was added 0.15 g (methyl bromide)cyclopropane and the resulting mixture was heated and boiled under reflux during the night. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water and concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from 80%aqueous solution of ethanol with obtaining, thus, 42 mg of white powdery 3-[2-(3-cyclopropylmethoxy-4-deformational)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,51 (1H, DD, J=4,8, 1.2 Hz), 7,60-7,53 (3H, m)to 7.50 (1H, s), 7,35-7,31 (1H, m), 7,21 (1H, d, J=8.1 Hz), of 6.68 (1H, t, J=75,3 Hz), 3,95 (2H, d, J=6.9 Hz), of 3.60 (2H, t, J=7.5 Hz), to 3.02 (2H, t, J=7.5 Hz,), 2,58 (3H, s), 1,37-1,25 (1H, m), is 0.69 to 0.63 (2H, m), 0,40-0,34 (2H, m).

Example 329

80 mg of the compound obtained in example 327, and 0.09 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 2 ml of ethanol, and then to the resulting solution were added 80 mg of 1-bromopropane on revali and boiled under reflux during the night. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from 80%aqueous solution of ethanol with obtaining, thus, 25 mg of white powdery 3-[2-(4-deformedarse-3-propoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,51 (1H, DD, J=4,8, 1.2 Hz), to 7.61-7,53 (3H, m)to 7.50 (1H, s), 7,35-7,31 (1H, m), 7,20 (1H, d, J=8.1 Hz), is 6.61 (1H, t, J=75 Hz), 4,07 (2H, t, J=6.6 Hz), of 3.60 (2H, t, J=7.5 Hz), to 3.02 (2H, t, J=7.5 Hz,), 2,58 (3H, s)to 1.87 (2H, TD, J=7,5, and 6.6 Hz), with 1.07 (3H, t, J=7.5 Hz).

Example 330

0.15 g of the compound obtained in example 327, and 0.18 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 3 ml of ethanol, and then to the resulting solution was added 0.15 g of allylbromide and was carried out by heating and boiling under reflux for 2 hours. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from 80%aqueous solution of ethanol with recip is observed thus, 70 mg of white powdery 3-[2-(3-allyloxy-4-deformational)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,51 (1H, DD, J=4,5, 1.2 Hz), 7,62-7,56 (3H, m)to 7.50 (1H, s), 7,50-7,31 (1H, m), 7,22 (1H, d, J=8,4 Hz), 6,62 (1H, t, J=75 Hz), 6,12-of 6.02 (1H, m), 5,46 (1H, DD, J=17.4 years, 1.5 Hz), 5,33 (1H, DD, J=10,8, 1,5 Hz), and 4.68 (2H, d, J=8.1 Hz), 3,61 (2H, t, J=7.2 Hz), to 3.02 (2H, t, J=7.2 Hz), 2,58 (3H, s).

Example 331

80 mg of the compound obtained in example 327, and 0.09 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene was dissolved in 2 ml of ethanol and then to the resulting solution were added 80 mg of 4-bromo-1-butene was carried out by heating and boiling under reflux overnight. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from 80%aqueous solution of ethanol with obtaining, thus, 22 mg of white powdery 3-[2-(3-but-3-enyloxy-4-deformational)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,51 (1H, DD, J=4,8, 1.2 Hz), to 7.61-rate of 7.54 (3H, m)to 7.50 (1H, s), 7,35-7,31 (1H, m), 7,20 (1H, d, J=8,4 Hz), 6,62 (1H, t, J=75 Hz), 5,98-of 5.83 (1H, m), 5,24-5,12 (2H, m)to 4.16 (2H, t, J=6.6 Hz), 3,61 (2H, t, J=7.2 Hz), 3,03 (2H, t, J=7.2 Hz), 2,64-of 2.58 (5H, m).

Example 332

,15 g of compound, obtained in example 327, and 0.18 ml of DBU were dissolved in 3 ml of ethanol, and then to the resulting solution was added 0.15 g of 2-bromopropane and was carried out by heating and boiling under reflux overnight. After cooling, to the reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from 80%aqueous solution of ethanol with obtaining, thus, 70 mg of white powdery 3-[2-(4-deformedarse-3-isopropoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-it.

1H-NMR (CDCl3) δ: 8,51 (1H, DD, J=4,8, and 0.9 Hz), 7,63-7,53 (3H, m)to 7.50 (1H, s), 7,35-7,31 (1H, m), 7,20 (1H, d, J=8.1 Hz), is 6.61 (1H, t, J=75 Hz), 4,73 with 4.65 (1H, m), 3,61 (2H, t, J=7.2 Hz), to 3.02 (2H, t, J=7.2 Hz), 2,58 (3H, s)of 1.39 (6H, d, J=6.0 Hz).

Example 333

Using the compound obtained in example 327, and ethyliodide white powdery 3-[2-(4-deformedarse-3-ethoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 330.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,5, 1.2 Hz), to 7.61-7,49 (4H, m), 7,35-7,30 (1H, m), 7,20 (1H, d, J=8,4 Hz), 6,62 (1H, t, J=75 Hz), 4,18 (2H, q, J=6.9 Hz), 3,61 (2H, t, J=7.2 Hz), to 3.02 (2H, t, J=7.2 Hz), 2,58 (3H, ), to 1.47 (3H, t, J=6.9 Hz).

Example 334

60 mg of the compound obtained in the ore 229, and 0.2 ml of DBU were dissolved in 4 ml of ethanol, and then to the resulting solution was added 0.2 ml of ethyliodide and was carried out by heating and boiling under reflux for 2 hours. After cooling, to the reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from ethanol to obtain, thus, 36 mg of white powdery 3-[2-(4-deformedarse-3-ethoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,5, 1.8 Hz), 7,60-7,34 (4H, m), 7,01-6,91 (2H, m), 7,20 (1H, d, J=8.1 Hz), 6,62 (1H, t, J=75 Hz), 4,22-4,07 (4H, m), of 3.43 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 1,50-of 1.40 (6H, m).

Example 335

0.15 g of the compound obtained in example 229, and 0.17 ml of DBU were dissolved in 4 ml of ethanol, and then to the resulting solution were added 0.14 g of allylbromide and was carried out by heating and boiling under reflux for 2 hours. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The floor is built of crystals was recrystallized from 80%aqueous solution of ethanol with obtaining, thus, 90 mg of white powdery 3-[2-(3-allyloxy-4-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,5, 1.8 Hz), 7,62-7,56 (2H, m), 7,46-7,40 (2H, m), 7,22 (1H, d, J=8.1 Hz), 7,01-6,92 (2H, m), 6,62 (1H, t, J=75 Hz), 6,15-6,00 (1H, m), the 5.45 (1H, DD, J=17,1, 1.5 Hz), 5,32 (1H, DD, J=10,5 and 1.5 Hz), of 4.67 (2H, d, J=8.1 Hz), 4,14 (2H, q, J=6.9 Hz), 3,42 (2H, t, J=7.5 Hz), of 3.00 (2H, t, J=7.5 Hz), to 1.48 (3H, t, J=6.9 Hz).

Example 336

0.12 g of the compound obtained in example 229, and 0.14 ml of DBU were dissolved in 3 ml of ethanol, and then to the resulting solution was added 0.12 g (methyl bromide)cyclopropane and was carried out by heating and boiling under reflux overnight. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from ethanol to obtain, thus, 80 mg of white powdery 3-[2-(3-cyclopropylmethoxy-4-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: 7,71 (1H, DD, J=7,8, 1.8 Hz), to 7.59-rate of 7.54 (2H, m), 7,46-7,40 (2H, m), 7,21 (1H, d, J=8.1 Hz), 7,01-to 6.95 (2H, m), of 6.68 (1H, t, J=75 Hz), 4,14 (2H, q, J=6.9 Hz), 3,95 (2H, d, J=6.9 Hz), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), of 1.47 (3H, t, J=6.9 Hz), 1,34 of 1.28 (1H, m), is 0.69 to 0.63 (2H, m), 0,40-0,34 (2H, m).

Por the measures 337

0.12 g of the compound obtained in example 229, and 0.14 ml of DBU were dissolved in 3 ml of ethanol, and then to the resulting solution was added 0.12 g of 4-bromo-1-butene was carried out by heating and boiling under reflux overnight. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from ethanol to obtain, thus, 80 mg of white powdery 3-[2-(3-but-3-enyloxy-4-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: of 7.70 (1H, DD, J=7,8, 1.8 Hz), to 7.61-rate of 7.54 (2H, m), 7,45-7,40 (2H, m), 7,20 (1H, d, J=8.1 Hz), 7,00-6,92 (2H, m), 6,62 (1H, t, J=75 Hz), 5,97-of 5.83 (1H, m), 5,23-5,12 (2H, m), 4,18-4,10 (4H, m), 3,42 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2,63-of 2.56 (4H, m)of 1.47 (3H, t, J=6.9 Hz).

Example 338

Using the compound obtained in example 97, and ethyliodide white powdery N-[2-(4-deformedarse-3-ethoxyphenyl)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,39 (1H, d, J=3.6 Hz), to 7.67-EUR 7.57 (4H, m), 7,33-7,20 (2H, m), 6,63 (1H, t, J=75 Hz), 4,60 (2H, d, J=5.7 Hz), 4,20 (2H, q, J=6.9 Hz), was 2.76 (3H, s)to 1.48 (3H, t, J=6.9 Hz).

Example 339

Using the compounds according to the scientists in example 97, and allylbromide white solid N-[2-(3-allyloxy-4-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,40-8,39 (1H, m), to 7.67 (1H, s), 7,65-7,58 (3H, m), 7,33-7,22 (3H, m), 6,63 (1H, t, J=75 Hz), 6,13-6,03 (1H, m), 5,50-5,32 (2H, m), 4,70-and 4.68 (2H, m), 4,60 (2H, d, J=8.7 Hz), was 2.76 (3H, ).

Example 340

Using the compound obtained in example 97, and 1-bromopropane white powdery N-[2-(4-deformedarse-3-propoxyphenyl)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, d, J=7,8 Hz), to 7.67-EUR 7.57 (4H, m), 7,33-7,20 (2H, m), 6,62 (1H, t, J=75 Hz), 4,60 (2H, d, J=6.0 Hz), 4,08 (2H, t, J=6.6 Hz), was 2.76 (3H, s), 1,94-to 1.82 (2H, m)of 1.07 (3H, t, J=7.5 Hz).

Example 341

Using the compound obtained in example 97, and 2-bromopropane white solid N-[2-(4-deformedarse-3-isopropoxyphenyl)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 is 8.38 (1H, m), to 7.67-EUR 7.57 (4H, m), 7,33-7,19 (2H, m), 6,62 (1H, t, J=75 Hz), 4,74-of 4.67 (1H, m), 4,59 (2H, d, J=6.0 Hz), was 2.76 (3H, s)of 1.39 (6H, d, J=6.0 Hz).

Example 342

Using the compound obtained in example 97, and 3-bromopentane colorless oily N-{2-[4-deformedarse-3-(1-ethylpropoxy)phenyl]oxazol-4-ylmethyl}-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,40 is 8.38 (1H, m), and 7.7 (1H, C), 7,63-of 7.55 (3H, m), 7,33-7,20 (3H, m), is 6.61 (1H, t, J=75 Hz), 4,59 (2H, d, J=6.0 Hz), 4,33 (1H, cut, J=6.0 Hz), was 2.76 (3H, s), 1,79 is 1.70 (4H, m), and 0.98 (6H, t, J=7.2 Hz).

Example 343

Using the compound obtained in example 97, and 4-bromo-1-butene colorless oily N-[2-(3-but-3-enyloxy-4-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,40 is 8.38 (1H, m), to 7.67 (1H, s)of 7.64-7,58 (3H, m), 7,33-7,20 (2H, m), 6,63 (1H, t, J=75 Hz), 5,95 of 5.84 (1H, m), 5,23-5,13 (2H, m), br4.61-4,59 (2H, m), 4,18 (2H, t, J=6.6 Hz), was 2.76 (3H, ), 2,64-of 2.58 (2H, m).

Example 344

Using the compound obtained in example 97, and isobutyramide colorless oily N-[2-(4-deformedarse-3-isobutoxide)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,39 (1H, users), to 7.68 (1H, s), a 7.62 EUR 7.57 (3H, m), 7,33-7,20 (2H, m), is 6.61 (1H, t, J=75 Hz), 4,60 (2H, d, J=6.0 Hz), 3,88 (2H, d, J=6.3 Hz), was 2.76 (3H, s), 2,19-2,04 (1H, m)of 1.06 (6H, d, J=6.3 Hz).

Example 345

Using the compound obtained in example 97, and (methyl bromide)CYCLOBUTANE colorless oily N-[2-(3-cyclobutylmethyl-4-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 3.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,40 (1H, users), to 7.68 (1H, s)of 7.64-to 7.59 (3H, m), 7,33-7,20 (2H, m), is 6.61 (1H, t, J=75 Hz), 4,60 (2H, d, J=6.0 Hz), 4,08 (2H, d, J=6.6 Hz), 2,89 was 2.76 (4H, m), 2,25-2,12 (2H, m), 2,04-1,92 (4H, m).

Example 346

the use of compounds obtained in reference example 46, and 2-ethoxybenzoyl acid white powdery N-[2-(3-benzyloxy-4-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 96.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,73 (1H, d, J=1.8 Hz), 7.68 per-to 7.61 (2H, m), of 7.48-7,24 (7H, m), 7,07 (1H, t, J=8.1 Hz), to 6.95 (1H, d, J=8,4 Hz), 6,63 (1H, t, J=75 Hz), to 5.21 (2H, s), 4,63 (2H,, d, J=5.4 Hz), 4,18 (2H, q, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz).

Example 347

Using the compound obtained in example 346, white powdery N-[2-(4-deformedarse-3-hydroxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 97.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,71-of 7.60 (2H, m), EUR 7.57 (1H, DD, J=8,4, 1.8 Hz), 7,46-7,39 (1H, m), 7,19 (1H, d, J=8,4 Hz), 7,07 (1H, t, J=8.1 Hz), to 6.95 (1H, d, J=8,4 Hz), is 6.61 (1H, t, J=73,2 Hz), of 6.02 (1H, users), with 4.64 (2H, DD, J=5,4, and 0.9 Hz), 4,19 (2H, q, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz).

Example 348

80 mg of the compound obtained in example 347, and 0.1 ml of DBU were dissolved in 2 ml of ethanol, and then to the resulting solution were added 80 mg of isobutyramide and was carried out by heating and boiling under reflux overnight. After cooling, to the resulting reaction mixture was added water and was carried out by extraction with ethyl acetate. The organic layer was twice washed with water, concentrated under reduced pressure and the obtained residue was purified column chromatography on silica compound is barely (n-hexane:ethyl acetate = 3:1). The obtained crystals are recrystallized from 80%aqueous ethanol to obtain, therefore, 30 mg of white powdery N-[2-(4-deformedarse-3-isobutoxide)oxazol-4-ylmethyl]-2-ethoxybenzene.

1H-NMR (CDCl3) δ: 8,54 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), to 7.67 (1H, s), 7,66-EUR 7.57 (2H, m), 7,45-7,39 (1H, m), 7.23 percent (1H, d, J=8.1 Hz), 7,07 (1H, t, J=8.1 Hz), to 6.95 (1H, d, J=7.5 Hz), 6,62 (1H, t, J=75 Hz), with 4.64 (2H,, d, J=5,1 Hz), 4,19 (2H, q, J=6.9 Hz), a 3.87 (2H, d, J=6.6 Hz), 2,17 (1H, cut, J=6.6 Hz), for 1.49 (3H, t, J=6.9 Hz), with 1.07 (6H, d, J=6,9 Hz).

Example 349

Using the compound obtained in example 347, and ethyliodide white powdery N-[2-(4-deformedarse-3-ethoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), to 7.67-7,58 (3H, m), 7,46-7,40 (1H, m), 7.24 to 7,21 (1H, m), was 7.08 (1H, t, J=7.8 Hz), to 6.95 (1H, d, J=7.8 Hz), only 6.64 (1H, t, J=75 Hz) 4,63 (1H, d, J=5,1 Hz), 4,23-to 4.15 (4H, m), 1,52 of 1.46 (6H, m).

Example 350

Using the compound obtained in example 347 1-bromopropane white powdery N-[2-(4-deformedarse-3-propoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,5, 1.8 Hz), to 7.67 (1H, s)of 7.64-EUR 7.57 (2H, m), 7,46-7,40 (1H, m), 7.23 percent (1H, d, J=7.8 Hz), 7,07 (1H, t, J=7.5 Hz), to 6.95 (1H, d, J=8,4 Hz), 6,63 (1H, t, J=75 Hz), with 4.64 (2H,, d, J=5.4 Hz), 4,19 (2H, q, J=7.2 Hz), 4,07 (2H, t, J=6.6 Hz), 1,90 (2H, cut, J=7,2, and 6.6 Hz), for 1.49 (3H, t, J=6.9 Hz), a 1.08 (3H, t, J=7.2 Hz)./p>

Example 351

Using the compound obtained in example 347, and allylbromide white powdery N-[2-(3-allyloxy-4-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,55 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,68 (1H, s), 7,65-of 7.60 (2H, m), 7,46-7,40 (1H, m), 7,25-of 7.23 (1H, m), was 7.08 (1H, t, J=7.8 Hz), of 6.96 (1H, d, J=8,4 Hz), only 6.64 (1H, t, J=74,7 Hz), 6,10-6,03 (1H, m), vs. 5.47 (1H, DD, J=17.4 years, 1.5 Hz), of 5.34 (1H, DD, J=a 10.5, 1.5 Hz), 4,69 (2H, dt, J=5,1, 1.5 Hz), 4,63 (2H, DD, J=5,4, 1.2 Hz), 4,19 (2H, q, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz).

Example 352

Using the compound obtained in example 347, and 2-bromopropane white powdery N-[2-(4-deformedarse-3-isopropoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,24 (1H, DD, J=7,5, 1.8 Hz), to 7.67 (1H, s), the 7.65 EUR 7.57 (2H, m), 7,46-7,40 (1H, m), 7,26-7,21 (1H, m), was 7.08 (1H, t, J=7.5 Hz), to 6.95 (1H, d, J=8,4 Hz), 6,63 (1H, t, J=75 Hz), 4,74-to 4.62 (3H, m), 4,19 (2H, q, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz), of 1.40 (6H, d, J=6.3 Hz).

Example 353

Using the compound obtained in example 347, and (methyl bromide)cyclopropane white powdery N-[2-(3-cyclopropylmethoxy-4-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,55 (1H, users), 8,24 (1H, DD, J=8,1, 1.8 Hz), to 7.67 (1H, s), to 7.61-7,58 (2H, m), 7,46-7,39 (1H, m), 7,26-7,21 (1H, m), 7,07 (1H, t, J=7.5 Hz), to 6.95 (1H, d, J=8,4 Hz), 6,70 (1H, t, J=75 Hz), 4,63 (2H, DD, J=5,4, 09 Hz), 4,19 (2H, q, J=6.9 Hz), for 1.49 (3H, t, J=6.9 Hz), 1,35-of 1.30 (1H, m), 0,71-of 0.64 (2H, m), 0,41-0,35 (2H, m).

Example 354

Using the compound obtained in example 347, and 4-bromo-1-butene white powdery N-[2-(3-but-3-enyloxy-4-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,5, 1.8 Hz), to 7.67 (1H, s)of 7.64-7,58 (2H, m), 7,46-7,40 (1H, m), 7,26-7,21 (1H, m), was 7.08 (1H, t, J=7.5 Hz), to 6.95 (1H, d, J=8,4 Hz), only 6.64 (1H, t, J=75 Hz), of 5.92 and 5.86 (1H, m), 5,24-5,13 (2H, m), with 4.64 (2H, d, J=5,1 Hz), 4,22-to 4.14 (4H, m), 2,65-of 2.58 (2H, m), for 1.49 (3H, t, J=6.9 Hz).

Example 355

Using the compound obtained in example 347, and 3-bromopentane white powdery N-{2-[4-deformedarse-3-(1-ethylpropoxy)phenyl]oxazol-4-ylmethyl}-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: to 8.57 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), to 7.67 (1H, s), 7,63-7,58 (2H, m), 7,46-7,40 (1H, m), 7.23 percent (1H, d, J=8,4 Hz), 7,07 (1H, t, J=8.1 Hz), to 6.95 (1H, d, J=8.1 Hz), 6,63 (1H, t, J=75 Hz), with 4.64 (2H,, d, J=5,1 Hz)to 4.33 (1H, cut, J=6,0, 5,1 Hz), 4,19 (2H, q, J=6.9 Hz), 1,79 is 1.70 (4H, m), for 1.49 (3H, t, J=6.9 Hz), 0,99 (6H, t, J=7.5 Hz).

Reference example 94

Using the compound obtained in reference example 59, and Chlorodifluoromethane white powdery ethyl 4-benzyloxy-3-deformationof was obtained by following the procedure of example 4.

1H-NMR (CDCl3) δ: of 7.90-7,80 (2H, m), 7,45-7,30 (5H, m), 7,03 (1H, d, J=8,4 Hz), 6,59 (1H, t, J=74,4 Hz), 5,23 (2H, s), 4,35 (2H, q, J=7.2 Hz), to 1.38 (3H, t, J=7.2 Hz)./p>

Reference example 95

Using the compound obtained in referential example 94, a white powdery 2-(4-benzyloxy-3-deformational)-4-chlormethiazole was obtained following the procedures of reference examples 3-5.

1H-NMR (CDCl3) δ: of 7.90-7,80 (2H, m), the 7.65 (1H, s), 7,45-7,30 (5H, m), 7,06 (1H, d, J=7,2 Hz), 6,60 (1H, t, J=74,7 Hz), 5,20 (2H, s), 4,56 (2H, s).

Example 356

Using the compound obtained in reference example 95, white powdery 3-{2-(3-deformedarse-4-hydroxyphenyl)oxazol-4-yl}-1-(3-methylpyridin-2-yl)propane-1-he received following the procedures of reference examples 92 and 93 and examples 326 and 327.

1H-NMR (CDCl3) δ: 8,49 (1H, d, J=4.5 Hz), 7,76-7,72 (2H, m), to 7.59 (1H, d, J=8,4 Hz), EUR 7.57 (1H, s), 7,37-7,30 (1H, m), 7,02 (1H, d, J=8,4 Hz), 6,59 (1H, t, J=75 Hz)and 3.59 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), to 2.57 (3H, s).

Example 357

Using the compound obtained in example 356, and 2-bromopropane white powdery 3-[2-(3-deformedarse-4-isopropoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), 7,83 for 7.78 (2H, m), 7,58 (1H, d, J=8,4 Hz), 7,47 (1H, s), 7,34-7,30 (1H, m), 7,01 (1H, d, J=8,4 Hz), to 6.58 (1H, t, J=75 Hz), 4,67-of 4.57 (1H, m)and 3.59 (2H, t, J=7.5 Hz), 3,01 (2H,, t, J=7.5 Hz), to 2.57 (3H, s)of 1.39 (6H, d, J=6.0 Hz).

Example 358

Using the compound obtained in example 356, and allylbromide white powdery 3-[2-(4-allyloxy-3-deformational)oxazol-4-yl]--(3-methylpyridin-2-yl)propane-1-he got following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,8, 1.2 Hz), 7,84-7,80 (2H, m), 7,60-7,56 (1H, m), 7,47 (1H, d, J=1.2 Hz), 7,34-7,30 (1H, m), 7,01 (1H, d, J=8,4 Hz), 6,60 (1H, t, J=74,7 Hz), 6,10-6,00 (1H, m), 5,44 (1H, DD, J=17.4 years, 1,5 Hz), 5,33 (1H, DD, J=a 10.5, 1.5 Hz)and 4.65 (2H, dt, J=5,1, 1.5 Hz), of 3.60 (2H, t, J=7.5 Hz), a 3.01 (2H, t, J=7.5 Hz), 2,58 (3H, s).

Example 359

Using the compound obtained in example 356, and 4-bromo-1-butene white powdery 3-[2-(4-but-3-enyloxy-3-deformational)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,8, 1.2 Hz), 7,84 for 7.78 (2H, m), 7,58 (1H, d, J=7.5 Hz), 7,46 (1H, s), 7,34-7,30 (1H, m), 7,00 (1H, d, J=8,4 Hz), 6,59 (1H, t, J=75 Hz), 5,94-to 5.85 (1H, m), 5,23-5,12 (2H, m), of 4.12 (2H, t, J=6.6 Hz), of 3.60 (2H, t, J=7,2 Hz)of 3.00 (2H, t, J=7.2 Hz), 2,63-of 2.56 (5H, m).

Example 360

Using the compound obtained in example 356, and (methyl bromide)cyclopropane white powdery 3-[2-(4-cyclopropylmethoxy-3-deformational)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,8, 1.2 Hz), 7,83-7,79 (2H, m), EUR 7.57 (1H, d, J=7.5 Hz), 7,46 (1H, s), 7,34-7,30 (1H, m), 6,98 (1H, d, J=8.1 Hz), of 6.65 (1H, t, J=75 Hz)to 3.92 (2H, d, J=7,2 Hz)and 3.59 (2H, t, J=7.2 Hz), to 3.00 (2H, t, J=7.2 Hz), to 2.57 (3H, s), 1,33-of 1.27 (1H, m), is 0.69 to 0.63 (2H, m), 0,40-0,34 (2H, m).

Example 361

Using the compound obtained in example 356, and 1-bromopropane white powdery 3-[2-(3-deformedarse-4-propoxyphenyl)oxazol-4-yl]-1-(3-what ethylpyridine-2-yl)propane-1-he got following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, DD, J=4,8, 1.2 Hz), 7,84 for 7.78 (2H, m), 7,58 (1H, d, J=8.1 Hz), 7,47 (1H, s), 7,43-7,30 (1H, m), 7,00 (1H, d, J=8,4 Hz), 6,59 (1H, t, J=75 Hz), a 4.03 (2H, t, J=6.6 Hz)and 3.59 (2H, t, J=7.5 Hz,), a 3.01 (2H, t, J=7.5 Hz), 2,58 (3H, s)to 1.87 (2H, cut, J=7,2 Hz), of 1.06 (3H, t, J=7.2 Hz).

Example 362

Using the compound obtained in example 356, and ethyliodide white powdery 3-[2-(3-deformedarse-4-ethoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 8,50 (1H, d, J=4.5 Hz), 7,84 for 7.78 (2H, m), to 7.59 (1H, d, J=8,4 Hz), 7,47 (1H, s), 7,34-7,30 (1H, m), of 6.99 (1H, d, J=8,4 Hz), 6,60 (1H, t, J=75 Hz)to 4.15 (2H, q, J=6.9 Hz)and 3.59 (2H, t, J=7.2 Hz), a 3.01 (2H, t, J=7.2 Hz), to 2.57 (3H, s)of 1.47 (3H, t, J=6.9 Hz).

Example 363

Used the compound obtained in reference example 95, and was treated by following the procedure of example 228, with subsequent processing in accordance with the procedure of example 229 obtaining a white powdery 3-[2-(3-deformedarse-4-hydroxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-it.

1H-NMR (CDCl3) δ: 7,80 to 7.75 (2H, m), 7,71 (1H, DD, J=7,8, 1.8 Hz), 7,46-7,40 (2H, m), 7,22-6,69 (3H, m), 6,59 (1H, t, J=75 Hz), 5,91 (1H, users), 4,14 (2H, q, J=7.2 Hz), 3,42 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), 1,48 (3H, t, J=7.2 Hz).

Example 364

Using the compound obtained in example 363, and 4-bromo-1-butene white powdery 3-[2-(4-but-3-enyloxy-3-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-he shall receive the Lee, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,84-7,79 (2H, m), 7,71 (1H, DD, J=7,8, 1.8 Hz), 7,46-7,39 (2H, m), 7,01-6,92 (3H, m), 6,59 (1H, t, J=75 Hz), 5,91-to 5.85 (1H, m), 5,23-5,12 (2H, m), 4,18-4.09 to (4H, m), 3,42 (2H, t, J=6.9 Hz), 2,99 (2H, t, J=6.9 Hz), 2,60 (2H, m)to 1.48 (3H, t, J=6.9 Hz).

Example 365

Using the compound obtained in example 363, and allylbromide white powdery 3-[2-(4-allyloxy-3-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,83-7,79 (2H, m), of 7.70 (1H, DD, J=7,8, 1.8 Hz), 7,46-7,39 (2H, m), 7,02-6,92 (3H, m), 6,60 (1H, t, J=74,7 Hz), 6,06-6,00 (1H, m), 5,47-and 5.30 (2H, m), 4,66-4,63 (2H, m), 4,14 (2H, q, J=6.9 Hz), 3,42 (2H, t, J=6,9 Hz)to 2.99 (2H, t, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz).

Example 366

Using the compound obtained in example 363, and ethyliodide white powdery 3-[2-(3-deformedarse-4-ethoxyphenyl)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-received, following the procedure of example 3.

1H-NMR (CDCl3) δ: 7,84-7,80 (2H, m), 7,71 (1H, DD, J=7,8, 1.8 Hz), 7,45-7,39 (2H, m), 7,00-6,91 (3H, m), 6,60 (1H, t, J=75 Hz) 4,18-4,10 (4H, m), 3,42 (2H, t, J=7.5 Hz), 2,99 (2H, t, J=7.5 Hz), 1,50-of 1.44 (6H, m).

Reference example 96

Used the compound obtained in reference example 95, and was treated by following the procedure described in reference example 45, with subsequent processing in accordance with the procedure of reference example 46 to obtain a pale yellow oily [2-(4-benzyloxy-3-deformational)oxazol-4-yl]meth is lamina.

1H-NMR (CDCl3) δ: 7,89-of 7.82 (2H, m), to 7.61 (1H, s), 7,56-7,31 (5H, m), 7,07 (1H, d, J=8.1 Hz), 6,62 (1H, t, J=75 Hz), 5,19 (2H, s), 3,83 (2H, s).

Example 367

Used the compound obtained in reference example 96, and was treated by following the procedure of example 96, followed by processing in accordance with the procedure of example 97 by obtaining a white powdery N-[2-(3-deformedarse-4-hydroxyphenyl)oxazol-4-ylmethyl]-3-methylphthalimide.

1H-NMR (CDCl3) δ: 8,59 (1H, users), 8,39 (1H, d, J=4.5 Hz), 7,79-7,76 (2H, m), 7,63-7,58 (2H, m), 7,37-7,28 (1H, m), 7,07 (1H, d, J=8.1 Hz), is 6.61 (1H, t, J=75 Hz), 6,16 (1H, s), 4,58 (2H, d, J=5.4 Hz), was 2.76 (3H, s).

Example 368

Using the compound obtained in example 367, and allylbromide white powdery N-[2-(4-allyloxy-3-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,39 (1H, d, J=4.5 Hz), 7,87-7,83 (2H, m), the 7.65 (1H, s), 7,60-EUR 7.57 (1H, m), 7,33-7,29 (1H, m), 7,10 (1H, d, J=8,4 Hz), is 6.61 (1H, t, J=75 Hz), 6,10-of 5.99 (1H, m), of 5.55 (1H, DD, J=17,1, 1,5 Hz), of 5.34 (1H, DD, J=a 10.5, 1.5 Hz)and 4.65 (2H, d, J=5.4 Hz), 4,58 (2H, d, J=5.4 Hz), was 2.76 (3H, s).

Example 369

Using the compound obtained in example 367, and (methyl bromide)CYCLOBUTANE white powdery N-[2-(4-cyclobutylmethyl-3-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, d, J=4.5 Hz), 7,87-of 7.82 (2H, m), of 7.64 (1H, s), and 7.9 (1H, d, J=8,4 Hz), 7,33-7,29 (2H, m), 7,01 (1H, d, J=8,4 Hz), 6,59 (1H, t, J=75 Hz), 4,59 (1H, d, J=5.4 Hz), a 4.03 (2H, d, J=6.9 Hz), 2,90-2,82 (1H, m), was 2.76 (3H, s), 2,22 and 2.13 (2H, m), 2.00 in of 1.84 (4H, m).

Example 370

Using the compound obtained in example 367, and isobutyramide white powdery N-[2-(3-deformedarse-4-isobutoxide)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, d, J=4.5 Hz), 7,87-7,83 (2H, m), of 7.64 (1H, s), 7,60-EUR 7.57 (1H, m), 7,33-7,28 (1H, m), 7,00 (1H, d, J=8,4 Hz), 6,59 (1H, t, J=75 Hz), 4,59 (1H, d, J=5.4 Hz), 3,81 (2H, d, J=6,9 Hz), was 2.76 (3H, s), 2,22-of 2.09 (1H, m)of 1.06 (6H, d, J=6,6 Hz).

Example 371

Using the compound obtained in example 367, and 4-bromo-1-butene white powdery N-[2-(4-but-3-enyloxy-3-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: 8,59 (1H, users), 8,39 (1H, d, J=4.5 Hz), 7,88-7,83 (2H, m), the 7.65 (1H, s), 7,60-EUR 7.57 (1H, m), 7,33-7,29 (1H, m), 7,01 (1H, d, J=8,4 Hz), is 6.61 (1H, t, J=75 Hz), 5,94-of 5.83 (1H, m), 5,24-5,12 (2H, m), 4,59 (1H, d, J=5.4 Hz), of 4.13 (2H, t, J=6.6 Hz), was 2.76 (3H, s), 2,63-to 2.57 (2H, m).

Example 372

Using the compound obtained in example 367, and (methyl bromide)cyclopropane white powdery N-[2-(4-cyclopropylmethoxy-3-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, d, J=4.5 Hz), 7,86-7,83 (2H, m), the 7.65 (1H, s), to 7.59 (1H, d, J=8,4 Hz), 7,33-7,28 (1H, m), 7,0 (1H, d, J=8,4 Hz), 6,66 (1H, t, J=75 Hz), 4,59 (2H, d, J=5.4 Hz), 3,93 (2H, d, J=6.9 Hz), was 2.76 (3H, s), 1,33-1,24 (1H, m), 0.70 to of 0.64 (2H, m), 0,41-0,35 (2H, m).

Example 373

Used the compound obtained in reference example 96, and was treated by following the procedure of example 96, followed by processing in accordance with the procedure of example 97 by obtaining a white powdery N-[2-(3-deformedarse-4-hydroxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene.

1H-NMR (CDCl3) δ: 8,59 (1H, users), 8,24 (1H, DD, J=7,8, 1.2 Hz), 7,81 for 7.78 (2H, m), 7,63 (1H, s), 7,46-7,40 (1H, m), 7,11-7,05 (2H, m), of 6.96 (1H, d, J=8,4 Hz), 6,62 (1H, t, J=75 Hz), by 5.87 (1H, users), to 4.62 (2H, d, J=5.4 Hz), 4,19 (2H, q, J=6.9 Hz), 1,50 (3H, t, J=6.9 Hz).

Example 374

Using the compound obtained in example 373, and 2-bromopropane white powdery N-[2-(3-deformedarse-4-isopropoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,24 (1H, DD, J=7,8, and 2.1 Hz), the 7.85-of 7.82 (2H, m), of 7.64 (1H, s), 7,45-7,39 (1H, m), 7,09-7,01 (2H, m), to 6.95 (1H, d, J=8.1 Hz), 6,59 (1H, t, J=75 Hz), 4,71-br4.61 (5H, m), 4,19 (2H, q, J=6,9 Hz)and 1.51 (3H, t, J=6.9 Hz), of 1.40 (6H, d, J=6,9 Hz).

Example 375

Using the compound obtained in example 373, and (methyl bromide)cyclopropane white powdery N-[2-(4-cyclopropylmethoxy-3-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: 8,59 (1H, users), 8,24 (1H, DD, J=7,8, and 2.1 Hz), the 7.85-of 7.82 (2H, m), of 7.64 (1H, is), 7,45-7,39 (1H, m), 7,09-6,94 (3H, m), of 6.66 (1H, t, J=75 Hz), to 4.62 (2H, d, J=5.4 Hz), 4,19 (2H, q, J=6.9 Hz), 3,93 (2H, d, J=8,4 Hz), 1,50 (3H, t, J=6.9 Hz), 1,34-1,24 (1H, m), 0,71-of 0.64 (2H, m), 0,41-0,35 (2H, m).

Example 376

Using the compound obtained in example 373, and 1-bromopropane white powdery N-[2-(3-deformedarse-4-propoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,87-7,83 (2H, m), of 7.64 (1H, s), 7,42 (1H, t, J=7.5 Hz), 7,09-6,85 (3H, m), 6.35mm (1H, t, J=75 Hz), to 4.62 (2H, d, J=6.0 Hz), 4,19 (2H, q, J=6.6 Hz), Android 4.04 (2H,, t, J=6.0 Hz), 1,91-of 1.84 (2H, m)of 1.50 (3H, t, J=6.9 Hz), with 1.07 (3H, t, J=6.9 Hz).

Example 377

Using the compound obtained in example 373, and allylbromide white powdery N-[2-(4-allyloxy-3-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 98.

1H-NMR (CDCl3) δ: at 8.60 (1H, users), 8,23 (1H, DD, J=7,8, 1.8 Hz), 7,86-7,83 (2H, m), of 7.64 (1H, s), 7,42 (1H, t, J=7.5 Hz), 7,10-6,97 (3H, m), is 6.61 (1H, t, J=75 Hz), 6,07-6,01 (1H, m), 5,49-5,32 (2H, m), 4,68-br4.61 (4H, m), 4,19 (2H, q, J=6.9 Hz), 1,50 (3H, t, J=6.9 Hz).

Reference example 97

Using ethyl 3,4-dihydroxybenzoate and Chlorodifluoromethane white powdery ethyl 3,4-bis-deformationof was obtained by following the procedure of example 4.

1H-NMR (CDCl3) δ: 8,00-of 7.90 (2H, m), 7,31 (1H, d, J=8.1 Hz), 6,60 (1H, t, J=72,9 Hz), to 6.57 (1H, t, J=72,9 Hz), 4,39 (2H, q, J=7.2 Hz), of 1.40 (3H, t, J=7.2 Hz).

Reference example 98

Using with the organisations, obtained in reference example 97, the white powdery 2-(3,4-bis-deformational)-4-chlormethiazole was obtained following the procedures of reference examples 3-5.

1H-NMR (CDCl3) δ: 7.95 is-of 7.90 (2H, m), 7,73 (1H, s), 7,35 (1H, d, J=8,4 Hz), 6,60 (1H, t, J=72,9 Hz), 6,59 (1H, t, J=72,9 Hz), of 4.57 (2H, s).

Example 378

Using the compound obtained in reference example 98, white powdery 3-[2-(3,4-bis-deformational)oxazol-4-yl]-1-(2-ethoxyphenyl)propane-1-received, following the procedure of example 190.

1H-NMR (CDCl3) δ: 7,89-to 7.84 (2H, m), 7,71 (1H, DD, J=7,5, 1.8 Hz), of 7.48-7,41 (2H, m), 7,32 (1H, d, J=8,4 Hz), 7,01-6,93 (2H, m), to 6.58 (1H, t, J=75 Hz), to 6.57 (1H, t, J=75 Hz), 4,14 (2H, q, J=6.9 Hz), of 3.43 (2H, t, J=6,9 Hz)of 3.00 (2H, t, J=6.9 Hz), to 1.48 (3H, t, J=6.9 Hz).

Reference example 99

Used the compound obtained in reference example 98, and was treated by following the procedure described in reference example 45, with subsequent processing in accordance with the procedure of reference example 46 to obtain a pale yellow oily [2-(3,4-bis-deformational)oxazol-4-yl]methylamine.

1H-NMR (CDCl3) δ: 7,92-7,88 (2H, m), 7,58 (1H, s), 7,34 (1H, d, J=8,4 Hz), 6,60 (1H, t, J=75 Hz), 6,59 (1H, t, J=75 Hz), 3,85 (2H, s).

Example 379

Using the compound obtained in reference example 99, white powdery N-[2-(3,4-bis-deformational)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 96.

1H-NMR (DCl 3) δ: 8,61 (1H, users), 8,40 (1H, DD, J=7,5, 1.5 Hz), 7,93-7,88 (2H, m), of 7.70 (1H, s), 7,60 (1H, d, J=1.5 Hz), 7,58-7,31 (2H, m), 6,60 (1H, t, J=75 Hz), to 6.58 (1H, t, J=75 Hz), 4,60 (2H, DD, J=6,0, 1.2 Hz), 2,77 (3H, s).

Example 380

Using the compound obtained in reference example 99, white powdery N-[2-(3,4-bis-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 1.

1H-NMR (CDCl3) δ: 8,59 (1H, users), 8,23 (1H, DD, J=7,5, 1.8 Hz), 7,94-7,88 (2H, m), of 7.70 (1H, s), 7,46-7,33 (2H, m), 7,07 (1H, t, J=7.5 Hz), to 6.95 (1H, d, J=8,4 Hz), 6,60 (1H, t, J=75 Hz), 6,59 (1H, t, J=75 Hz), 4,63 (2H,, d, J=6.0 Hz), 4,19 (2H, q, J=6.9 Hz), 1,50 (3H, t, J=6.9 Hz).

Example 381

Using the compound obtained in reference example 98, white powdery 3-[2-(3,4-bis-deformational)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propane-1-received, following the procedure of example 356.

1H-NMR (CDCl3) δ: 8,51 (1H, users), 7,88-a 7.85 (2H, m), to 7.59 (1H, d, J=8,4 Hz), 7,53 (1H, s), 7,35-7,30 (2H, m), to 6.58 (1H, t, J=75 Hz), to 6.57 (1H, t, J=75 Hz), of 3.60 (2H, t, J=6.3 Hz), to 3.02 (2H, t, J=6.3 Hz), 2,58 (3H, ).

Example 382

Using the compound obtained in example 347, and compounds obtained in reference example 85, white powdery N-{2-[4-deformedarse-3-(2,2-diflorasone)phenyl]oxazol-4-ylmethyl}-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,55 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,71-the 7.65 (3H, m), 7,46-7,41 (1H, m), 7,29 (1H, s), was 7.08 (1H, t, J=8.1 Hz), of 6.96 (1H, d, J=8.1 Hz), 6,59 (1H, t, J=74,1 Hz) x 6.15 (1H, TT, J=54,9, 4,2 Hz) with 4.64 (2H, d, J=5.4 Hz), 4,32 (2H, TD, J=12,9, 4,2 Hz), 4,20 (2H, q, J=6.9 Hz), 1,50 (3H, t, J=6.9 Hz).

Example 383

Using the compound obtained in example 347, and 1,1,1-Cryptor-2-iodata white powdery N-{2-[4-deformedarse-3-(2,2,2-triptoreline)phenyl]oxazol-4-ylmethyl}-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), 7,75-to 7.68 (3H, m), 7,46-7,40 (1H, m), 7,30 (1H, d, J=8,4 Hz), was 7.08 (1H, t, J=8.1 Hz), of 6.96 (1H, d, J=8.1 Hz), 6,60 (1H, t, J=74,1 Hz), 4,63 (2H, d, J=5.4 Hz), of 4.49 (2H, q, J=8.1 Hz), 4,20 (2H, q, J=6.9 Hz), 1,50 (3H, t, J=6.9 Hz).

Example 384

Using the compound obtained in example 17 and 2-bromopropane colorless oily N-[2-(4-methoxy-3-isopropoxyphenyl)oxazol-4-ylmethyl]-3-methylpyridine was obtained by following the procedure of example 19.

1H-NMR (CDCl3) δ: 8,58 (1H, users), 8,39 (1H, DD, J=4,8, 1.2 Hz), 7,63-EUR 7.57 (4H, m), 7,33-7,28 (1H, m), 6,93 (1H, d, J=8,4 Hz), and 4.68 (1H, Sept., J=6.3 Hz), 4,59 (2H, d, J=5.7 Hz), with 3.89 (3H, s), was 2.76 (3H, s)of 1.41 (6H, d, J=6.3 Hz).

Example 385

Using the compound obtained in example 347, and (methyl bromide)CYCLOBUTANE white powdery N-[2-(3-cyclobutylmethyl-4-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene was obtained by following the procedure of example 348.

1H-NMR (CDCl3) δ: 8,56 (1H, users), 8,24 (1H, DD, J=7,8, 1.8 Hz), to 7.67-7,58 (3H, m), 7,50-7,40 (1H, m), 7.23 percent (1H, d, J=8,4 Hz), was 7.08 (1H, t, J=8.1 Hz), of 6.96 (1H, d, J=8.1 Hz), 6,63 (1H, t, J=75 Hz), with 4.64 (2H, d, J=5,1 Hz), 4,19 (2H, q, J=6,9 is C), 4,08 (2H, d, J=6.6 Hz), 2,86-2,82 (1H, m), 2,19-2,12 (2H, m), 2,04-to 1.87 (4H, m)of 1.50 (3H, t, J=6.9 Hz).

The chemical structure of the compounds obtained above in reference examples and examples are given below in table 1-40.

Table 1
№ Ref. approx.RaRb
5MethylBenzil
11Methyl
17Methyl
23Methyl-CH2CF3
32-CH2CF3
35EthylEthyl
38MethylMethyl
44 -CHF2Benzil
55BenzilBenzil
58MethylEthyl
63BenzilEthyl
68MethylIsopropyl

Table 2

-OEt: amoxi
No. approx.Rc
1Benzil
2H
3
4-CH2CF3
5n-Butyl
6Cyclopentyl
7
8
9Ethyl
10
11n-Propyl
12Isopropyl
13
14Isobutyl
15-CH2CH2CF3
92Methyl

Table 3
No. approx.Ara
252-Triptoreline
322-(2,2,2-Triptoreline)phenyl
372-Isopropoxyphenyl
382-Were
392-Ethylphenyl
40 2-Chlorophenyl
415-fluoro-2-methoxyphenyl
424-fluoro-2-methoxyphenyl
436-fluoro-2-methoxyphenyl
442-Methylthiophenyl
462-Methoxyphenyl
472-Trifloromethyl
482-n-Propoxyphenyl
512-n-Butoxyphenyl
522-Isobutoxide
542-Ethylthiophene
562,6-Acid
602-Methanesulfonyl

Table 4
No. approx.Arb
632-Methoxyphenyl
642-Methylthiophenyl
664-fluoro-2-methoxyphenyl
672-Isopropoxyphenyl
686-fluoro-2-methoxyphenyl
712-n-Propoxyphenyl
722-n-Butoxyphenyl
732-Isobutoxide

Table 5
No. approx.Arc
782-Methoxyphenyl
792-Were
802-n-Propoxyphenyl
812-Isopropoxyphenyl
824-Chloro-2-methoxyphenyl

Table 6
No. approx.Ard
852-n-Propoxyphenyl
862-Triptoreline
882-Ethoxyphenyl
894-Ethoxyphenyl
905-Methoxy-2-trifloromethyl
913-Ethoxyphenyl

Table 7
No. approx.AreRdRe
232-TriptorelineMethylBenzil
242-TriptorelineMethylH
26Triptoreline Methyl
302-(2,2,2-Triptoreline)phenylMethylBenzil
312-(2,2,2-Triptoreline)phenylMethylH
332-MethoxyphenylMethylBenzil
342-MethoxyphenylMethylH
352-MethoxyphenylMethylCyclopentyl
832-Ethoxyphenyl-CH2CF3
932-EthoxyphenylMethylMethyl

Table 8
No. approx.RRg
16MethylBenzil
17MethylH
18MethylCyclopentyl
19Methyl-CH2CF3
20MethylEthyl
21MethylAllyl
22Methyl
36Methyl
62MethylIsobutyl
84-CH2CF3
94MethylMethyl
96-CHF2Benzil
97-CHF2H
98-CHF2
384MethylIsopropyl

Table 9
No. approx.RhRi
27EthylBenzil
28EthylH
29EthylCyclopentyl
45H
50Ethyl
53 Isopropyl
57Methyl
58Isobutyl
61n-Propyl
65EthylIsobutyl
69MethylIsobutyl
70IsobutylIsobutyl
74IsopropylIsobutyl
76Methyl-CH2CF3
77Ethyl-CH2CF3
95MethylMethyl

Table 10
No. approx.ArfRjRk
49Methyl
55Methyl
59Methyl
75MethylIsobutyl
87EthylEthyl
99Methyl
Me: Methyl

Table 11
-OEt: Amoxi
No. approx.RlRm
101MethylH
102Methyl
103MethylEthyl
104MethylAllyl
105MethylCyclopentyl
106MethylIsobutyl
107Methyln-Propyl
108Methyl
109Methyln-Butyl
110Methyl
111MethylIsopropyl
112Methyl-CH2CF3
113Methyl
114Methyl
115Methyl
116Methyl
117Methyl
118Methyl
119Methyl
120Methyl
121Methyl
122Methyl
182EthylEthyl
190BenzilEthyl
191HEthyl
192IsopropylEthyl
228-CHF2Benzil
229-CHF2H
230-CHF2Isopropyl

Table 12
-OMe: Methoxy
No. approx.Rn
169Isopropyl
170
171Cyclopentyl
172Ethyl
173Isobutyl
174Allyl
175-CH2CF3

Table 13
No. approx.Ro
194H
195Ethyl
196Cyclopentyl
197Isopropyl
198
199
200Allyl
201
203-CH2CF3

Table 14
No. approx.Rp
207H
208
209Ethyl
210Isopropyl
211Allyl
212
213-CH2CF3
214

Table 15
No. approx.R
164Benzil
166Allyl
189Ethyl
224Isopropyl

Table 16
No. approx.Rr
220H
221
225Ethyl
226Allyl
227Isopropyl

Table 17

-OEt: amoxi
No. approx.Arg
1782-Allyloxyphenyl
1843-Ethoxyphenyl
1854-This is xifei
2052-n-Propoxyphenyl
2162-Isopropoxyphenyl
2182-Were

Table 18
No. approx.Chemical structure
165
168
176
179
223
231
232
233
234
235

Table 19
No. approx.Rs
136H
137
138Ethyl
139Isopropyl
140Allyl
141
142Isobutyl
143n-Propyl
144Cyclopentyl
145
146
147n-Butyl
148
149
150-CH2CH2Ph
151-CH2CH2CH2Ph
152
153
154
155-CH2CF3
156
157
158Cyclohexyl
159
Ph: Phenyl

Table 20
No. approx.RtRu
125Methyl H
126Methyl
127MethylIsobutyl
128MethylCyclopentyl
129Methyl-CH2CF3
131EthylH
132EthylCyclopentyl
133Ethyl
134EthylIsobutyl

Table 21
No. approx.Chemical structure
123
161
162
163
181
183
187
188

Table 22
No. approx.ArhRvRw
1932-n-PropoxyphenylMethylBenzil
2022-n-PropoxyphenylMethyl-CH2CF3
2042-n-PropoxyphenylEthylEthyl
2-IsopropoxyphenylMethylBenzil
2152-IsopropoxyphenylEthylEthyl
2172-WereEthylEthyl
2192-WereMethylBenzil
2222-BenzyloxyphenylMethylIsopropyl

Table 23
No. approx.AriRxRy
1002-EthoxyphenylMethylBenzil
1243-MethoxypyridineMethylBenzil
1303-EthoxypyridineMethylBenzil
1353-MethylpyridylMethylBenzil
1602-PyridylMethylBenzil
1672-MethoxyphenylMethylBenzil
1803-MethylpyridylEthylEthyl
1863-MethylpyridylBenzilBenzil

Table 24
No. approx.Chemical structure
236
237
238
239
240

Table 25
No. approx.Chemical structure
241
242
243
244
245

Table 26
No. approx.Chemical structure
246
247
248
249
250

Table 27
No. approx.Chemical structure
251
252
253
254
255
256

Table 28
No. approx.Chemical structure
257
258
259
260
261

Table 29
No. approx.Chemical structure
262
263
264
265

Table 30
№ Ref. approx.Chemical structure
89
90
91
92
93
95

Table 31
№ Ref. approx.Chemical structure
96
98
99

Table 32
-OEt: Amoxi
No. approx.RARB
325Methyl1-Ethylpropyl
346DeformityBenzil
347Deformity H
348DeformityIsobutyl
349DeformityEthyl
350Deformityn-Propyl
351DeformityAllyl
352DeformityIsopropyl
353DeformityCyclopropylmethyl
354Deformity3-Butenyl
355Deformity1-Ethylpropyl
373HDeformity
374IsopropylDeformity
375CyclopropylmethylDeformity
376n-Propyl Deformity
377AllylDeformity
380DeformityDeformity
382Deformity2.2-Dottorati
383Deformity2,2,2-Triptorelin
385DeformityCyclobutylmethyl

Table 33
No. approx.RCRD
324Methyl1-Ethylpropyl
338DeformityEthyl
339DeformityAllyl
340Deformityn-Propyl
341DeformityIsopropyl
342Deformity1-Ethylpropyl
343Deformity3-Butenyl
344DeformityIsobutyl
345DeformityCyclobutylmethyl
367HDeformity
368AllylDeformity
369CyclobutylmethylDeformity
370IsobutylDeformity
3713-ButenylDeformity
379DeformityDeformity

Table 34
-OEt: Amoxi
No. approx.RERF
313MethylDeformity
314Methyl2.2-Dottorati
315Methyl2-Foradil
334DeformityEthyl
335DeformityAllyl
336DeformityCyclopropylmethyl
337Deformity3-Butenyl
363HDeformity
3643-ButenylDeformity
365Allyl366EthylDeformity
378DeformityDeformity

Isopropyl
Table 35
No. approx.RGRH
308MethylDeformity
309Methyl2.2-Dottorati
310Methyl2-Foradil
311Methylsecond-Butyl
312Methyl1-Ethylpropyl
317H2.2-Dottorati
318Ethyl2.2-Dottorati
3192.2-Dottorati
327DeformityH
328DeformityCyclopropylmethyl
329Deformityn-Propyl
330DeformityAllyl
331Deformity3-Butenyl
332DeformityIsopropyl
333DeformityEthyl
356HDeformity
357IsopropylDeformity
358AllylDeformity
3593-ButenylDeformity
360C is capability Deformity
361n-PropylDeformity
362EthylDeformity
381DeformityDeformity

Table 36
No. approx.RIRJRK
267MethylBenzilDeformity
268MethylBenzil2-Foradil
269MethylBenzil2.2-Dottorati
270MethylHDeformity
271 MethylH2-Foradil
272MethylH2.2-Dottorati
273MethylIsopropylDeformity
274MethylEthylDeformity
275MethylIsopropyl2-Foradil
276Methyl3-Butenyl2-Foradil
277MethylIsobutyl2-Foradil
278MethylIsopropyl2.2-Dottorati
279Methyln-Propyl2.2-Dottorati
280MethylEthyl 2.2-Dottorati
281MethylAllyl2.2-Dottorati
282Methyl3-Butenyl2.2-Dottorati
283MethylCyclopropylmethyl2.2-Dottorati
284Methyl2.2-Dottorati2.2-Dottorati
285MethylIsobutyl2.2-Dottorati
288EthylEthylDeformity
289EthylEthyl2-Foradil
290EthylEthyl2.2-Dottorati
292EthylEthylTrifluoromethyl
293MethylCyclopropylmethylTrifluoromethyl

Table 37
No. approx.Chemical structure
266
286
287
291
294
295

Table 38
No. approx.Chemical structure
296
297
298
299
300
301
302
303

Table 39
No. approx.Chemical structure
304
305
306
307
316
320
321

Table 40
No. approx.Chemical structure
322
323
326

The test example 1

The test for determining the activity of inhibiting phosphodiesterase(PDE)4

(1) preparation of plasmids in large scale

The plasmids containing genes (HPDE4D)encoding cDNA PDE4D3 person (stored in Otsuka America Pharmaceutical, Inc., Maryland Research Laboratories), transformed inE. colicultivated in large quantities, and was purified using a kit EndoFree™ Plasmid Maxi Kit (Qiagen).

(2) Abundant expression and purification PDE4D

Cells COS-7, isolated from the kidneys of African green monkeys were cultured with subcultures in the medium D-MEM containing 100 units/ml penicillin, 100 μg/ml streptomycin and 10% FBS. The cells were transfusional the plasmid obtained in (1) above, using Lipofectamine™ 2000 (hereinafter indicated as “LF2000”, Invitrogen)following the manufacturer's Protocol. Cells COS-7 inoculable 10-cm Cup for culturing the day before transfection to obtain on the day of transfection 90% confluence the t cells. Cups for cultivation, where each contained a solution of plasmid (solution A), in which 24 µg plasmid was diluted in 1.5 ml medium Opti-MEM I Reduced Serum Medium (Invitrogen), and the solution LF2000 (solution B), in which 60 μl of LF2000 was dissolved in 1.5 ml of medium Opti-MEM I Reduced Serum Medium, separately left to stand for 5 minutes at room temperature. Solutions A and B were then mixed and the mixture was allowed to stand for 20 minutes at room temperature. The mixture was added to cultured cells and incubated at 37°C (5% CO2) during the night. The next day the medium was replaced and the mixture is again incubated overnight to collect the cells as follows. Cells were washed once using PBS (Sigma), and in each Cup for cultivation was added 10 ml Trypsin-EDT (Sigma). After the solution was distributed into each Cup for cultivation, the cells were peeled off, and the cups were allowed to stand for approximately 5 minutes at 37°C. Separated from the cups of cells suspended in the medium, were collected in centrifuge tubes and centrifuged at 1200 rpm./min for 5 minutes at 4°C and supernatant was removed by means of filtration. Cells then were washed using PBS and stored at -80°C. the Buffer KHEM (100 mm Hepes, 50 mm KCl, 10 mm EGTA, 1,92 mm MgCl2, a pH of 7.4)containing 1 mm DTT, 1 μg/ml antipain, 1 μg/ml Aprotinin, 1 μg/ml leupeptin, 1 μg/ml peptide is Tatina A, 157 µg/ml of benzamidine and 120 μg/ml Pefabloc SC, was added to the collected cells and all of this was transferred to a glass homogenizer for homogenization on ice. The cell suspension was centrifuged at 1000 rpm./min for 5 minutes at 4°C and supernatant was again centrifuged at 14000 rpm./min for one hour. After centrifugation the supernatant was distributed in new tubes as PDE4D enzyme solution and kept in the freezer for a deep freeze.

(3) determination of the degree of dilution PDE4D enzyme solutions

Enzyme solutions PDE4D obtained in (2) above, was dissolved in a solution of 20 mm Tris-HCl (pH 7,4) with 10-, 25-, 50-, 100-, 200-, 400 - and 800-fold dilutions of enzyme solutions. The PDE4D activity was measured as described in (4) below. Expected percentage catalyzed cAMP to the total number of cAMP, and this dilution, in which the percentage ranged from 10% to 30%, used in the test of inhibition, described below.

(4) Measurement of activity of inhibition of PDE4D

Was given the required number of the test compounds was added thereto 100% dimethyl sulfoxide (DMSO) to bring the concentration to 10 mm. The solutions were stored in the freezer as a source of solutions of each test compound. After thawing, when it was necessary, solutions of 20-fold diluted using 100% DMSO with the doctrine of concentration of 500 μm. Then received a 10-fold serial dilution using 100% DMSO to obtain the test compounds in different concentrations. 2 μl of solutions containing one of the concentrations of the test compounds was separately added in 1.2-ml test tube, in which in advance had been made 23 μl of 20 mm Tris-HCl (pH 7,4). 25 μl of PDE4D enzyme solution with an optimal degree of dilution, defined in (3) above, was added to each tube on ice and in a test tube was added 50 μl of substrate solution containing 2 μm[3H]cAMP, obtained by dilution buffer 20 mm Tris-HCl (pH 7,4)containing 10 mm MgCl2. The final concentration of DMSO in the reaction liquid was 2%. After mixing, the mixture is incubated for 10 minutes at 30°C. after the incubation, the tubes were placed in a bath of boiling water for 3 minutes and the reaction stopped. After cooling the tubes on ice was added 25 μl of a solution of 0.2 mg/ml snake venom, and after mixing the mixture is incubated for 10 minutes at 30°C. after the incubation was added 0.4 ml of a solution of resin Dowex 1×8, obtained in EtOH:H2O (1:1). After mixing, the tubes were allowed to stand at room temperature for at least an hour. 50 μl of supernatant from each tube was placed in one of the holes of the accounts tablet topCount and the plate was dried over night.3H radioacti the activity (imp./min) was measured using a TopCount TM.

Values IR50(concentration providing 50% inhibition of the hydrolysis of the substrate) for the test compounds was determined using a statistical software package Excel (Microsoft Excel 2000 SR-1), using regression analysis.

The results are presented in table 41. The table shows that the compounds represented by formula (I)possess excellent activity of inhibiting PDE4.

In the structural formulas shown in the table below, Me means methyl group, Et means ethyl group, -OMe means methoxy group, -OEt means ethoxypropan and-SMe means metalcorp.

Table 41

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

Table 41 (continued)

The test example 2

Measurement of the activity of inhibiting production of TNF-α

The activity of inhibiting production of TNF-α was determined in accordance with the following tests.

(1) Isolation of mononuclear cells from the peripheral blood of the mouse

Mononuclear cells were isolated from heparinized blood obtained from male BALB/c mice (Charles River Laboratories, Japan), by centrifugation in a density gradient using Lympholyte-M (Cedarlane Laboratories). The number of viable cells in the mononuclear cells of peripheral blood were calculated using dye Trypanosoma blue and prepared in cell culture medium (RPMI medium 1640 containing 10% FCS) to 1.25×106cells/ml

(2) Induction of the production of TNF-α

Test compounds were dissolved in DMSO and solutions of the test compounds were diluted for use in cell culture medium. 20 μl of solutions of the test compounds at various concentrations and 160 μl suspensions of mononuclear peripheral blood cells were placed in 96-well plates and were cultured for 30 minutes. Added 20 μl (final concentration 1 μg/ml) of lipopolysaccharide (LPS)derived fromE. coli(serotype 055:B5)to induce production of TNF-α. The mixture was then cultured at 37°C for 5 hours and the culture supernatant was removed from each Lu is key.

(3) Measurement of the concentration of TNF-α

Concentrations of TNF-α in the culture supernatant was measured by the method of ELISA (OptEIATMSet Mouse TNF-α, BD Pharmingen). Values IR50(the concentration which provides 50% inhibition of production of TNF-α) for the test compounds was determined using a statistical software package Excel (Microsoft Excel 2000 SR-1) using regression analysis.

The results obtained are presented in table 42.

Table 42
Test connectionTNF-α IR50(nm)
The compound of example 18<50
The compound of example 43<50
The compound of example 126<50
The compound of example 157<50
The compound of example 177<50

1. Connection oxazole represented by the formula (1)

where R1represents a phenyl group which may contain one or two substituent selected from the following groups (1-1)to(1-11):
(1-1) a hydroxy-group,br/> (1-2) unsubstituted or halogen-substituted lower alkoxygroup,
(1-3) lower alkenylacyl,
(1-4) lower alkyloxy,
(1-5) ciclos3-8alkyl(lower)alkoxygroup,
(1-6) ciclos3-8alkyloxy,
(1-7) ciclos3-8alkenylacyl,
(1-8) dihydroindolone,
(1-9) hydroxy(lower)alkoxygroup,
(1-10) oxiranyl(lower)alkoxygroup, and
(1-11) phenyl(lower)alkoxygroup;
R2represents a phenyl group or a heterocyclic group selected from pyridine, pyrazine, isoquinoline, pyrrolidine, piperazine, the research, each of which may contain one or two substituent selected from the following groups (2-1)to(2-10):
(2-1) a hydroxy-group,
(2-2) unsubstituted or halogen-substituted lower alkoxygroup,
(2-3) unsubstituted or halogen-substituted lower alkyl group,
(2-4) of the lower alkenylacyl,
(2-5) the atoms of halogen,
(2-6) the lower alcoholnye group,
(2-7) of the lower allylthiourea,
(2-8) the lower alkylsulfonyl group,
(2-9) the carbonyl group and
(2-10) group, a lower alkoxy-lower alkoxy; and
W represents a divalent group represented by the formula (i) or (ii):
-Y1-A1(i)
-Y2-C(=O)- (ii)
where a1represents the lowest alkenylamine group or lower alkylenes group which may contain one Deputy, wybran the th group, consisting of hydroxy-group and lower alkoxycarbonyl group,
Y1represents a simple bond, -C(=O)-, -C(=O)-N(R3)-, -N(R4)-C(=O)-, -S(O)m-NH - or-S(O)n-,
where R3and R4each independently represent a hydrogen atom or a lower alkyl group, and m and n each independently represent an integer having a value of 2
Y2represents piperazinyl group, or a divalent group represented by the formula (iii) or (iv)
-C(=O)-And2-N(R5)- (iii)
And3-N(R6)- (iv)
where a2and3, each independently, represent lower alkylenes group, R5and R6each independently represent a hydrogen atom;
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where R1represents a phenyl group which has 1 or 2 substituent selected from the following groups: (1-2), (1-3), (1-4) and (1-5):
(1-2) unsubstituted or halogen-substituted lower alkoxygroup,
(1-3) lower alkenylacyl,
(1-4) lower alkyloxy and
(1-5) ciclos3-8alkyl(lower)alkoxygroup;
R2represents a phenyl group or pyridyloxy group, each of which may contain 1 or 2 substituent selected from the group consisting of the following: (2-2), (2-3), (2-4) and (2-5):
(2-2) unsubstituted or halogenation the e lower alkoxygroup,
(2-3) unsubstituted or halogen-substituted lower alkyl group,
(2-4) of the lower alkenylacyl and
(2-5) the atoms of halogen;
W represents a divalent group represented by the formula (i)
-Y1-And1-, (i)
in which And1represents the lowest alkylenes group, and
Y1represents-C(=O)- or-C(=O)-N(R3)-,
where R3represents a hydrogen atom.

3. The compound according to claim 2, where R1represents a phenyl group containing two substituent selected from the following groups: (1-2), (1-3), (1-4) and (1-5):
(1-2) unsubstituted or halogen-substituted lower alkoxygroup,
(1-3) lower alkenylacyl,
(1-4) lower alkyloxy and
(1-5) ciclos3-8alkyl(lower)alkoxygroup;
R2represents a phenyl group or pyridyloxy group, each of which may contain from 1 to 2 substituents, selected from the following groups: (2-2), (2-3), (2-4) and (2-5):
(2-2) unsubstituted or halogen-substituted lower alkoxygroup,
(2-3) unsubstituted or halogen-substituted lower alkyl group,
(2-4) of the lower alkenylacyl and
(2-5) halogen atoms; and
W represents a divalent group represented by the formula (i)
-Y1-A1-, (i)
in which And1represents the lowest alkylenes group and Y1represents-C(=O)- or-C(=O)-N(R3)-, g is e R 3represents a hydrogen atom.

4. The compound according to claim 3, where R1represents a phenyl group substituted in the phenyl ring two lowest alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one ciclos3-8alkyl-(lower)alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one halogen-substituted lower alkoxygroup, phenyl group, substituted phenyl group, a single lower alkoxygroup and one lower alkynylamino, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one lower alkynylamino, or phenyl group, substituted phenyl ring two halogen-substituted lower alkoxygroup;
R2represents the lowest alkoxyphenyl group, lower altneratively group, halogen-substituted lower alkoxyphenyl group, lower alkylpyridinium group or a phenyl group substituted in the phenyl ring by one lower alkoxygroup and one halogen atom; and
W represents a divalent group represented by the formula (i)
-Y1-Asup> 1-, (i)
in which And1represents a C1-4alkylenes group and
Y1represents-C(=O)- or-C(=O)-N(R3)-,
where R3represents a hydrogen atom.

5. The compound according to claim 4, where R1represents a phenyl group substituted in the phenyl ring two lowest alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one ciclos3-8alkyl-(lower)alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one halogen-substituted lower alkoxygroup, phenyl group, substituted phenyl ring one lower alkoxygroup and one lower alkynylamino, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, phenyl group, substituted phenyl ring with one halogen-substituted lower lower alkoxygroup and one lower alkynylamino, or phenyl group, substituted phenyl ring two halogen-substituted lower alkoxygroup;
R2represents the lowest alkoxyphenyl group, lower altneratively group, halogen-substituted lower alkoxyphenyl group, lower alkylpyridinium group or a phenyl group substituted in FeNi is enom ring one lower alkoxygroup and one halogen atom; and
W represents a divalent group represented by the formula (i)
-Y1-A1-, (i)
in which And1represents a C1-4alkylenes group and
Y1represents-C(=O)-.

6. The compound according to claim 4, where R1represents a phenyl group substituted in the phenyl ring by one lower alkoxygroup and one halogen-substituted lower alkoxygroup, phenyl group, substituted phenyl ring with one halogen-substituted lower alkoxygroup and one ciclos3-8alkyl(lower)alkoxygroup, or a phenyl group substituted in the phenyl ring with one halogen-substituted lower alkoxygroup and one lower alkynylamino;
R2represents the lowest alkoxyphenyl group or lower alkylpyridinium group; and
W represents a divalent group represented by the formula (i)
-Y1-And1-, (i)
in which And1represents a C1-4alkylenes group and
Y1represents-C(=O)-N(R3)-,
where R3represents a hydrogen atom.

7. Pharmaceutical composition for treatment or prevention of diseases mediated by phosphodiesterase 4 and/or mediated by tumor necrosis factor a, containing the compound or pharmaceutically acceptable salt according to any one of claims 1 to 6 as the active ingr diente and a pharmaceutically acceptable carrier.

8. Pharmaceutical composition for treatment or prevention of atopic dermatitis, where the composition includes a compound or pharmaceutically acceptable salt according to any one of claims 1 to 6.

9. The use of compound or pharmaceutically acceptable salt according to any one of claims 1 to 6 as a medicinal product having the properties of an inhibitor of phosphodiesterase (PDE) 4 and/or inhibitor of tumor necrosis factor α (TNF-α).

10. The use of compound or pharmaceutically acceptable salt according to any one of claims 1 to 6 as an inhibitor of phosphodiesterase 4, and/or inhibiting the production of tumor necrosis factor α.

11. Method for the treatment or prevention of diseases mediated by phosphodiesterase 4 and/or mediated by tumor necrosis factor α, including the introduction of an effective dose of a compound or pharmaceutically acceptable salt according to any one of claims 1 to 6 human or animal.

12. The compound or its pharmaceutically acceptable salt according to claim 6, which is chosen from the group consisting of the following compounds:
N-[2-(4-deformedarse-3-isobutoxide)oxazol-4-ylmethyl]-3-methylpyridine,
N-[2-(3-cyclobutylmethyl-4-deformational)oxazol-4-ylmethyl]-3-methylpyridine,
N-[2-(4-deformedarse-3-isobutoxide)oxazol-4-ylmethyl]-2-ethoxybenzene,
N-[2-(4-deformedarse-3-ethoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene,
N-[2-(3-allyloxy-4-debtor ethoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene,
N-[2-(4-deformedarse-3-isopropoxyphenyl)oxazol-4-ylmethyl]-2-ethoxybenzene,
N-[2-(3-cyclopropylmethoxy-4-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene and
N-[2-(3-but-3-enyloxy-4-deformational)oxazol-4-ylmethyl]-2-ethoxybenzene.



 

Same patents:

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SUBSTANCE: invention relates to (3-trifluromethylphenyl)amide 6-(6-hydroxymethylpyrimidin-4-yloxy)naphthalene-1-carboxylic acid or tautomer or salt thereof. The invention also relates to a pharmaceutical composition which has protein kinase inhibiting activity, based on the said compound and use of the said compound to prepare pharmaceutical compositions for use in treating protein kinase dependent diseases, preferably proliferative diseases, particularly tumorous diseases.

EFFECT: improved properties of compounds.

6 cl, 115 ex

FIELD: chemistry.

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Aromatic compound // 2416608

FIELD: chemistry.

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62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel benzo[d]isoxazol-3-ylamine compounds of formula I in free form or in form of salts with physiologically compatible acids, having antagonistic effect on KCNQ2/3 ion channel. In formula I , R1, R2, R3 and R4 independently denote H, F, CI, Br, I, -NR7R8, -OR9 or C1-C10alkyl, R5 denotes -C(=S)NR21R22 or (CHR6)n-R25, where n equals 1, 2 or 3, R6 denotes H or C1-C6 alkyl, R25 denotes aryl or heteroaryl, R7 and R8 independently denote H or C1-C10 alkyl, R9 denotes H, C1-C10alkyl or -(C1-C5alkylene)aryl, R21 denotes H, R22 denotes C1-C10alkyl, C2-C10alkenyl, C3-C8cycloalkyl, -(C1-C5alkylene)-C3-C8cycloalkyl, -(C1-C3alkylene)heterocycloalkyl, aryl, heteroaryl or -(C1-C5alkylene)aryl, wherein each of the heterocycloalkyl residues has 5-6 members, contains 1 or 2 heteroatoms in the ring, independently selected from oxygen and nitrogen, each of the aryl residues is phenyl, anthracenyl or naphthyl, each of the heteroaryl residues has 5 or 6 members and contains 1 or 2 heteroatoms in the ring, independently selected from oxygen, sulphur and nitrogen.

EFFECT: said compounds can be used to prepare a medicinal agent for curing pain, migraine, anxiety, uroclepsia or epilepsy.

17 cl, 203 ex

FIELD: chemistry.

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EFFECT: high efficiency of the composition.

84 cl, 12 tbl, 1 dwg, 217 ex

FIELD: chemistry.

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EFFECT: novel compounds are obtained and described, which have a wide range of curative effect on mental disorders, including central nervous system disorders, without side effects and with high degree of safety.

22 cl, 3110 ex, 314 tbl

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21 cl, 3 tbl, 151 ex

FIELD: medicine, pharmaceutics.

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EFFECT: production of the compounds for therapy of the disease which depends on renin activity.

28 cl, 1 tbl, 375 ex

FIELD: chemistry.

SUBSTANCE: invention relates to azole derivatives of formula I , where: A denotes S, O; W denotes -(C=O)-; X are identical or different and denote =C(-R)- or =N-; Y denotes -O- or -NR1-; R denotes hydrogen, halogen, (C1-C6)-alkyl, nitro; R1 denotes hydrogen; R2 denotes (C5-C16)-alkyl, (C1-C4)alkyl-phenyl, where phenyl can be optionally mono- or poly-substituted with (C1-C6)-alkyl; R3 denotes hydrogen; or R2 and R3 together with the nitrogen atom bearing them can form a monocyclic saturated 6-member ring system, where separate members of this ring system can be substituted with 1 group selected from the following: -CHR5-, -NR5-; R5 denotes (C1-C6)-alkyl, trifluoromethyl; and physiologically acceptable salts thereof. The invention also pertains to methods of producing said compounds and a medicinal agent based on said compounds.

EFFECT: novel compounds and a medicinal agent based on said compounds are obtained, which can be used as hormone-sensitive lipase (HSL) or endothelial lipase (EL) inhibitors.

12 cl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds 2,6-di-tert.-butyl-4-{2-[2-(methylamino)ethyl]-1,3-thiazole-4-yl}phenol, 2,6-di-tert.-butyl-4-[4-(hydroxymethyl)-1,3-oxazole-2-yl]phenol, 4-methylphenyl-2-[4-(1,1-biphenyl-4-yl)-1H-imidazole-2-yl]ethylcarbamate and others or their pharmaceutically acceptable salts. Also, invention relates to using these compounds for preparing a medicinal agent possessing one of the following three activities: inhibition of monoamine oxidases activity, inhibition of lipids peroxidation and modulating activity with respect to sodium channels. Proposed derivatives of thiazole, oxazole or imidazole possess one of the following species of pharmacological activity: inhibition of monoamine oxidases activity, inhibition of lipids peroxidation and modulation of sodium channels.

EFFECT: valuable biochemical and biological properties of derivatives.

34 cl, 119 ex

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention relates to compounds of the formula (1) , their N-oxides and salts that can be used in agriculture wherein values A, B, J, R1, R3, R4 and n are given in the invention claim. Also, invention describes a method for control of arthropoda pests to provides high productivity that comprises applying the effective dose of compound of the formula (1) on arthropoda pests and in medium of their habitation, and a the composition with arthropocide activity comprising compounds of the formula (1).

EFFECT: valuable properties of compounds and composition.

23 cl, 34 tbl, 759 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a compound of general formula (I), involving steps in accordance with the following scheme:

, where at separate steps: a) a compound of formula (IX) is converted to a compound of formula (V) in the presence of an enzyme selected from lipase B from Candida antarctica, b) the compound of formula (V), in the presence of an acid catalyst through effect of a compound which can form a protective group Z3 which is stable in alkaline medium and labile in acidic medium, is converted to a compound of formula (VIII) and c) the compound of formula (VIII) is converted to a compound of formula (II) in the presence of a nucleophilic agent; d) in the presence of a base B1, the compound of formula (II) is converted through effect of a compound of formula (VI) to a compound of formula (IIIa); e) the compound of formula (IIIa) is converted to a compound of formula (IVa), where the corresponding conversion is carried out through effect of an alcohol in the presence of an acid catalyst; f) through the effect of the compound (VII), the compound (IVa) is converted to a compound of formula (Ia) in the presence of a base B1 and g) if needed, the compound (Ia) is hydrolysed or hydrogenolysed to a compound of formula (I), if R3 denotes H; wherein the compound (IX) is a pure cis-isomer or a mixture of cis/trans-isomers, respectively; variables and substitutes assume the following values, respectively: ring A is C3-C8cycloalkyl, R1, R2, R4 and R5 independently denote , F, CI, Br, C1-C6alkyl or -O-(C1-C6alkyl); R3 denotes H, C1-C6alkyl; R6 denotes C1-C6alkyl or benzyl; X denotes C1-C6alkyl; Y denotes C1-C6alkyl; Z1 denotes a protective group which is stable in acidic medium; Z2 denotes a protective group which is stable in acidic medium; Z3 denotes a protective group which is stable in alkaline medium and labile in acidic medium; Z4 denotes a leaving group; Z5 denotes a leaving group; B1 denotes a tertiary alcoholate of an alkali-earth metal, a tertiary alcoholate of an alkali metal, an amide of an alkali-earth metal, an amide of an alkali metal, a silazide of an alkali-earth metal, a silazide of an alkali metal or a hydride of an alkali metal. The invention also relates to a method of producing a compound of general formula (I), involving steps in accordance with the following scheme:

, where at separate steps: a2) through at least one acyl group donor and in the presence of an enzyme selected from lipase B from Candida antarctica, the compound of formula (X) is converted to a compound of formula (V); steps b) - g) are described above, wherein the compound (X) is a pure cis-isomer or a mixture of cis/trans-isomers respectively. The invention also relates to a compound of general formula (IIIa), where ring A is cyclohexyl, where the X-containing and Z3-containing substitutes are in the cis-1,3-position of the cyclohexyl fragment; R1, R2 and R4 independently denote H, F, Cl, C1-C3alkyl or -C(O)-(C1-C6alkyl); Z3 denotes tetrahydropyranyl; X denotes methyl, and to a compound of general formula (VIII), where ring A is cyclohexyl, wherein the Z1-containing and Z3-containing substitutes are in the cis-1,3-position of the cyclohexyl fragment; Z1 denotes -C(O)CH3; Z3 denotes tetrahydropyranyl.

EFFECT: efficient method of obtaining the said compound.

14 cl, 5 dwg, 2 tbl, 27 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to the following compounds: N-(1-{4-[2-(1-acetylamino-ethyl)-1-ethyl-1H-imidazol-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trofluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-methyl-1-hydroxy-ethyl)-1-ethyl-1H-imidazole-4-yl}-benzyl}-3-hydroxy-propyl)-3-chloro-4-(,2,2,2-trifluoro-1-methyl-ethoxy)-benzamide, N-(1-{4-[2-(1-hydroxy-1-methyl-ethyl)-1-methyl-1H-imidazole-4-yl]-benzyl}-3-hydroxy-propyl)-3-chloro-4-(2,2,2,-trifluoro-1-methyl-ethoxy)-benzamide, 3-chloro-N-[2-[(N,N-dimethylglicyl)amino]-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)ethyl]-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-(1-(2-(dimethylamino)acetamido)-3-(4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl)propan-2-yl)-4-isopropoxybenzamide, 3-chloro-N-(2-[(2-methylalanyl)amino]-1-{[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]methyl}ethyl)-4-[(1-methylethyl)oxy]benzamide, 3-chloro-N-[(3-hydroxy)-1-({4-[8-(1-hydroxyethyl)imidazo[1,2-a]pyridine-2-yl]phenyl}methyl)propyl]-4-[(1-methylethyl)oxy]benzamide, as well as to their pharmaceutically acceptable salts.

EFFECT: obtained compounds and salts can be used for treatment cell proliferative diseases and disorders by modulating activity of mitotic kinesin CENP-E.

26 cl, 102 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent which modulates PPARδ (peroxisome proliferator-activated receptor δ). In formula I

, p is equal to 1; L2 is selected from a group which includes -XOX- and -XSX-, where X is independently selected from a group which includes a bond and C1-C4alkylene; R13 is selected from a group which includes halogen, C1-C6alkyl; R14 is selected from a group which includes -XOXC(O)OR17 and -XC(O)OR17, where X denotes a bond or C1-C4alkylene and R17 denotes hydrogen; R15 and R16 are independently selected from a group which includes -R18 and -YR18, where Y is selected from a group which includes C2-C6alkenylene, and R18 is selected from a group which includes C6-C10aryl, pyridinyl, pyrimidinyl, quinolinyl, benzo[b]furanyl, benzoxazolyl, 1,5-benzodioxanyl, 1,4-benzodioxanyl and 3,4-dihydro-2H-benzo[b][1,4]dioxepin; where any of phenyl, pyridinyl, pyrimidinyl, benzoxazolyl in R18 is independently substituted with 1-2 radicals, independently selected from a group which includes halogen, C1-C6alkyl, C2-C7alkenyl, C1-C6alkoxy group, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxy group, C3-C12cycloalkyl, phenyl, morpholinyl, pyrrolidinyl, piperidinyl, -XNR17R17, -XC(O)NR17R17, -XC(O)R19 and -XOXR19, where X denotes a bond or C1-C4alkylene; R17 is selected from a group which includes C1-C6alkyl, and R19 is selected from a group which includes C3-C12cycloalkyl, piperidinyl and phenyl. The invention also relates to use of the disclosed compounds to prepare a medicinal agent which modulates PPARδ activity, a pharmaceutical composition having PPARδ activity modulating properties, which contains a therapeutically effective amount of the disclosed compound and to use of the pharmaceutical composition in preparing a medicinal agent which modulates PPARδ activity.

EFFECT: improved properties of compounds.

10 cl, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to derivatives of (R)-2-arylpropionamides of general formula I, in which Ar is phenyl group, substituted in 3(meta) position by group R1, selected from: linear or branched C1-C8-alkanoyl, C3-C6- cycloalkanoyl, heteroarylcarbonyl, C1-C6-alkylaminocarbonyl, arylaminocarbonyl, C1-C6-alkylamino, C1-C6-acylamino, arylamino, benzoylamino, aryloxy, heteroaryl, C1-C6-alkoxycarbonyl, C6-aryloxycarbonyl, C1-C8-alkansulfonyl, arylsulfonyl, or 3,4-dihydro-1H-quinolyl-2-on; R is selected from: -H, OH; - heteroaryl group is selected from: pyridine, pyrimidine, pyrrole, thiophene, furan, indole, thiazole, oxazole; - α or β carboxyl residue can consist of straight or branched C1-C6-alkyl, C3-C6-cycloalkyl, optionally substituted with other carboxyl (COOH) group; - residue with formula SO2Rd, in which Rd is C1-C6-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl or pyridyl, on condition that compounds of formula I are not the following compounds: (R)-2-(3-phenoxyphenyl)-propanoyl-phenylglycine; (R)-2-( phenoxyphenyl)-propanoyl-glycine; (R)-2-[(3'-acetyl)phenyl]-R-4''-pyrimidyl)propionamide. Invention also relates to method of obtaining formulaI compound and application of formula I compound for preparation of medications for treatment of diseases including C5a induced hemotaxis of human PMNs.

EFFECT: obtained are novel derivatives of (R)-2-arylpropionamide, possessing useful biological properties.

9 cl, 3 dwg, 2 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing oxazoles of formula IV through condensation of aromatic aldehydes with α-ketoximes with formation of the corresponding N-oxides and their subsequent reaction with sulphonyl or thionyl compounds, preferably with inorganic thionyl halides or organic sulphonyl halides.

EFFECT: method is characterised by high output and purity of the obtained product, as well as avoiding the need to extract unstable intermediate N-oxides in form of individual compounds.

12 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I) and their pharmaceutically acceptable salts and esters. The disclosed compounds have LXR-alpha and/or LXR-beta agonist properties. In formula (I) R1 is hydrogen, halogen; R2 is lower alkyl, flouro-lower alkyl; R3 is hydrogen, phenyl; R4 is hydrogen, hydroxy; R5 is hydrogen; phenyl; R6 is phenyl, a 5-6-member heteroaryl with one or two heteroatoms selected from nitrogen and sulphur, a 9-member bicyclic heteroaryl with a sulphur atom as a heteroatom, which can be optionally substituted with a halogen, or R6 is , R7 is a lower alkyl; R8 is phenyl which is optionally substituted with one substitute selected from a group consisting of halogen, fluoro-lower alkyl, R9-O-C(O)-, R10R11NC(O)-, phenyl-lower alkoxy; R9, R10, R11 independently represent hydrogen or lower alkyl; L is a single bond, lower alkylene or lower alkenylene; m assumes values from 0 to 3; n is equal to 0 or 1.

EFFECT: obtaining a new compound and a pharmaceutical composition which contains the disclosed compound as an active ingredient for therapeutic and/or preventive treatment of diseases.

23 cl, 47 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel hexafluoroisopropanol-substituted ether derivatives of formula (I) to their pharmaceutically acceptable salts and to esters which are capable of bonding with LXR-alpha and/or LXR-beta, as well as to pharmaceutical compositions based on said compounds. In formula (I) R1 is hydrogen, lower alkyl or halogen, one of groups R2 and R3 is hydrogen, lower alkyl or halogen, and the second of groups R2 and R3 is -O-CHR4-(CH2)m-(CHR5)n-R6. Values of R4, R5, R6 m and n are given in the formula of invention.

EFFECT: novel compounds have useful biological properties.

22 cl, 4 dwg, 102 ex

FIELD: chemistry.

SUBSTANCE: invention relates to versions of the method of producing chiral non-racemic compound of formula I where R1 represents . Values of the rest of the radicals are given in the formula of invention. Formula I compound is obtained in several steps. The starting material used is cis-1,3-cyclohexanediol. One of the key steps is enzymatic formation of ester or enzymatic splitting of ester.

EFFECT: method is described for production of enantiomeric forms of derivatives of 1,3-cyclohexanedio in cis orientation.

8 cl, 80 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , in which A is selected from one or several X and/or Y groups; X represents methylene group; Y represents C2-alkinylene group; n represent integer number from 1 to 5; R1 represents group R2, optionally substituted with one or several R3 and/or R4 groups; R2 represents group selected from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphtyl, chinolinyl, isochinolinyl, dihydroisochinolinyl, 2-oxo-3,4-dihydrochinolinyl, indolyl, benzimidazolyl, pyrrolopyridinyl; R3 represents group selected from halogen atoms, groups C1-6-alkyl, C3-7-Cycloalkyl, C1-6-alkoxy, NR5R6 and phenyl; R4 represents group selected from groups: phenyl, naphtyl, pyridinyl; R4 group or groups can be substituted with one or several R3 groups, similar or different from each other; R5 and R6 independently on each other represent C1-6-alkyl group; R7 represents hydrogen atom or C1-6-alkyl group; R8 represents hydrogen atom or group C1-6-alkyl, C3-7-cycloalkyl, C3-7-Cycloalkyl- C1-3-alkylene; in form of base, acid-additive salt, hydrate or solvate. Invention also relates to methods of obtaining formula (I) compound by any of ii. 1-3, to compounds, determined by general formula (IV), (VII), to pharmaceutical composition, as well as to application of formula (I) compounds by any of ii. 1-3.

EFFECT: obtaining novel biologically active compounds possessing activity of enzyme FAAH inhibitors.

10 cl, 5 ex, 1 tbl

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