Derivatives of guanidine, the retrieval method, the method of inhibition of na+/h+- metabolism in cells

 

(57) Abstract:

Describes the new guanidine derivatives of the formula (I), where Y is a group N or C-R1in which R1is hydrogen, lower alkyl, hydroxy-group, and so on; R2is hydrogen, aryl which may have one acceptable Deputy, alloctype and so on ; R3is hydrogen, lower alkoxygroup, the hydroxy-group, and so on; Z - group N or C-R4in which R4is hydrogen, halogen, hydroxy(lower)alkyl, etc. ; W is a group N or C - R12in which R12is hydrogen, and their pharmaceutically acceptable salts, used as medicines for the treatment and/or prevention of myocardial infarction and ischemic arrhythmias in humans or animals. In addition, disclosed is a method of obtaining these guanidine derivatives and their salts. 3 S. and 12 C.p. f-crystals, 1 PL.

The invention relates to new derivatives of guanidine and their pharmaceutically acceptable salts, used as medicines.

Disclosure of the invention

This invention relates to new derivatives of guanidine. More specifically, this invention relates to new derivatives of guanidine and their pharmaceutically acceptable salts with pharmaco is ptx2">

Accordingly, one objective of this invention is to obtain useful new guanidine derivatives and their pharmaceutically acceptable salts, having a strong inhibitory effect on the Na+/H+-exchange in cells.

Another objective of the invention is to provide methods of obtaining guanidine derivatives and their salts.

Another objective of the invention to provide dosage forms containing guanidine derivatives or their pharmaceutically acceptable salts.

And another objective of the invention is to provide methods of use of these guanidine derivatives or their pharmaceutically acceptable salts as drugs for the treatment and/or prevention of cardiovascular diseases, cerebrovascular diseases, renal diseases, arteriosclerosis, shock, etc. in humans and animals.

Target guanidine derivatives of the present invention are new compounds which can be represented by the following General formula (I):

< / BR>
where Y represents N or C-R1in which R1represents hydrogen, (lower)alkyl; hydroxy; (lower)alkoxygroup; hydroxy(lower)alkyl; protected amino(nissink group, having as the heteroatoms are 1 or 2 nitrogen atom;

R2represents hydrogen; aryl which may have one Deputy, selected from the group comprising: halogen, nitro, cyano, (lower)alkyl, trihalogen (lower)alkyl, protected amino group; alloctype; trihalogen (lower)alkyl; acyl; 5 - or 6-membered heterocyclic group with 1 to 4 heteroatoms, independently selected from the group comprising nitrogen, sulfur and oxygen, which may have a substituent(s) selected(s) from the group that includes: carboxypropyl, secure carboxypropyl, acyl, (lower)alkyl, halogen, Gerasimenko(lower)alkyl, di(lower)alkylamino(lower) alkyl, cyano, amino, protected amino, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, carboxy (lower)alkyl; or a heterocycle(lower)alkyl;

R3represents hydrogen, (lower)alkoxygroup; a hydroxy-group, 5-membered heterocyclic group with the nitrogen atom as a heteroatom; or

R2and R3- connected to each other with the formation of 2-valent radical of the formula:

< / BR>
in which R5is hydrogen or (lower)alkyl;

R6is hydrogen or (lower)alkyl;

R11is hydrogen or cyano;

Z lkyl; 5-membered heterocyclic group with 1 to 4 nitrogen atoms as heteroatoms; acyl; W is N or C-R12in which R12represents hydrogen; or a pharmaceutically acceptable salt of this compound.

The target compounds of formula (I) of the present invention can be synthesized in the following way (see the end of the description).

Suitable pharmaceutically acceptable salts of the target compounds of formula (I) are conventional non-toxic salts, which may include salts with bases or salts formed by addition of acids, such as salts with inorganic bases, for example alkali metal salts (e.g. sodium salt, potassium salt, etc.), salts of alkaline earth metals (e.g. calcium salt, magnesium salt etc), ammonium salts; salts with organic bases, for example salts with organic amines (for example, a salt with triethylamine, salt with pyridine, picoline salt and, salt with ethanolamine, salt and triethanolamine salt with dicyclohexylamine, salt with N,N'-dibenziletilendiaminom and so on ); salts formed by the addition of inorganic acid (e.g. hydrochloride, hydrobromide, sulfate, phosphate, etc.); salts formed by adding an organic carboxylic econsultant, bansilalpet, toluensulfonate and so on); salts with amino acids of either acidic or basic in nature (for example, the arginine, aspirational acid, glutamic acid and so on),

In the above and the text below this description, examples and illustrations of various definitions, deliberately included in the scope of the invention is explained in detail below.

The term "lower(traveler" is used to denote a group having 1-6, preferably 1-4, carbon atoms, unless otherwise specified.

The term "Executive(AE) is used to denote a group having 7-20 carbon atoms, unless otherwise specified.

Suitable "lower alkyl" and "lower alkyl fragment" in terms of "protected hydroxy(lower)alkyl", "hydroxy(lower) alkyl", "amino(lower)alkyl", "protected amino(lower)alkyl, heterocycle(lower)alkyl", "mono(di or three) halogen(lower) alkyl", "di(lower)alkylamino(lower)alkyl", hydroxyimino (lower)alkyl" and "(lower)alkoxy(lower)alkyl" includes alkyl straight or branched chain and 1-6 carbon atoms, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert - butyl, tert-pentyl, pentyl, hexyl, etc., preferably Alki the Boxing(lower)alkenyl" and "protected carboxy (lower)alkenyl" may include vinyl, 1-(or 2-)-propenyl, 1-(2 - or 3-)butenyl, 1-(2-, 3 - or 4-)pentenyl, 1-(2-3-, 4 - or 5-)hexenyl, methylvinyl, ethyl vinyl, 1-(2 - or 3-methyl-1-(or 2-)propenyl, 1-(2 - or 3-) ethyl-1-(or 2-)propenyl, 1-(2-, 3 - or 4-)methyl-1-(2 - or 3-)butenyl and so on, of which more preferred(C2-C4)alkenyl.

Suitable "lower quinil may include: ethinyl, 1 - PROPYNYL, propargyl, 1-methylpropenyl, 1-, 2 - or 3-butynyl, 1-, 2-, 3 - or 4-pentenyl, 1-, 2-, 3-, 4- or 5-hexenyl etc.

Suitable "lower alkoxygroup" or "lower alkoxy - fragment" in the terms "(lower)alkoxy(lower)alkyl", "carboxy (lower)alkoxygroup", "protected carboxy(lower)alkoxy group", "hydroxy(lower)alkoxygroup" and "protected hydroxy (lower)alkoxygroup" may include methoxy, ethoxy-, propoxy-, isopropoxy, butoxy, isobutoxy-, tert-butoxy-, pentyloxy-, tert-pentyloxy-, hexyloxy etc.

Suitable "cyclo(lower)alkyl" may include: cyclopentyl, cyclohexyl, etc.

Suitable "cyclo(lower)alkenyl may include: cyclohexenyl, cyclohexadienyl etc.

Suitable "protected amino" and "protected amino - fragment" in the term "protected amino(lower)alkyl" may include protected ordinary about what kinogruppa or amino group, protected by a conventional protecting group such as ar(lower) alkyl, which contains the acceptable substituent(for example, benzyl, trityl and so on), or a similar group.

Suitable "acyl" and "acyl fragment" in the term "acyl - amino group" may include: carbarnoyl, aliphatic acyl group and acyl group contained in the aromatic cycle, which is called as aromatic acyl, or heterocyclic nucleus, which is known as heterocyclic acyl.

These atilov can be illustrated with the following acceptable examples; carbarnoyl, thiocarbamoyl, sulfamoyl, aliphatic acyl, such as lower and upper alkanoyl (for example, formyl, acetyl, propanol, butanol, 2-methylpropanol, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanol, deletion, pentadecanol, hexadecanol, heptadecanol, octadecanol, nonadecanoic, eicosanoic and so on), the lowest or highest alkoxycarbonyl (for example, methoxycarbonyl, etoxycarbonyl, tert-butoxycarbonyl, tert-pentyloxybenzoyl, heptyl)oxycarbonyl and so on), lower or higher alkylsulfonyl (for example, methylsulphonyl, ethylsulfonyl and so on ), or lower volkischer (for example, pharmacysulfacet, diplomatischer, trifloromethyl, chloromethanesulfonyl, dichloromethylsilane, trichloromethylsulfuryl, 1 - or 2 - foreteller, 1-or 2-Kharatishvili and so on) or a similar group.

Aromatic atilov include, for example, aroyl (for example, benzoyl, toluoyl, naphtol and so on), ar(lower)alkanoyl (for example, phenyl(lower)alkanoyl (for example, phenylacetyl, phenylpropanol, phenylmethanol, phenylethanol, phenylmethanol, phenylhexanoic and so on); naphthyl(lower)alkanoyl (for example, naphthylacetyl, afterrepair, a naphthyl butanol and so on), and so on); ar(lower)alkanoyl (for example, phenyl(lower)alkanoyl (for example, phenylpropenoyl, phenylmethanol, phenylmethanol, phenylmethanol, phenylhexanoic and so on ), naphthyl(lower)alkanoyl (for example, afterproperties, afterburner and so on), and so on); ar(lower)alkoxycarbonyl (for example, phenyl(lower)alkoxycarbonyl (for example, benzyloxycarbonyl), and so on); aryloxyalkyl (for example, phenoxycarbonyl, naphthalocyanines and so on); aryloxy- (lower)alkanoyl (for example, phenoxyacetyl, phenoxypropionyl and so on ); acilglycerol (for example, phenylglyoxylic, naphthyl - glyoxylyl and so on), arylsulfonyl (for example, phenylsulfonyl, p-tamilselvan and so dkl(lower)alkanoyl (for example, heterocyclization, heterostrophic, the heterocycle butanol, heterocyclization, heterosiloxanes and so on), heterocycle(lower)alkanoyl (for example, getawallpaper, the heterocycle butanol, heterocyclization, geterotsiklicheskie and so on), heterozygosity and similar groups in which the "heterocyclic fragment" for the terms "heterocyclicamines, heterocycle(lower)alkyl, heterocycle (lower)alkanoyl and heterozygosity" mentioned above, more specifically, means a saturated or unsaturated, monocyclic or polycyclic heterocyclic radical containing at least one heteroatom such as oxygen atom, sulfur, nitrogen, etc.

Particularly preferred heterocyclic groups include heterocyclic groups, such as:

unsaturated 3 to 8-membered (more preferably 5 - or 6-membered) heterogenities group containing 1-4 nitrogen atoms, for example pyrrolyl, pyrrolidyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridin, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl and so on), tetrazolyl (for example, 1H-tetrazolyl 2N-tetrazolyl and so on and so forth;

saturated 3 to 8-membered (more p is Il, imidazolidinyl, piperidyl, piperazinil etc.;

unsaturated condensed heterocyclic group containing 1-4 nitrogen atom, for example, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, hinely, ethanolic, indazoles, benzotriazolyl etc.;

unsaturated 3 to 8-membered (more preferably 5 - or 6-membered heterogenities group containing 1-2 oxygen atoms and 1-3 nitrogen atom, for example oxazolyl, isoxazolyl, oxadiazolyl (for example, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl and so on and so forth;

saturated 3 to 8-membered (more preferably 5 - or 6-membered) heterogenities group containing 1-2 oxygen atoms and 1-3 nitrogen atom, such as oxazolidinyl, morpholinyl, sentinel etc.;

unsaturated condensed heterocyclic group containing 1-2 oxygen atoms and 1-3 nitrogen atom, for example, benzoxazolyl, benzoxadiazole etc.;

unsaturated 3 to 8-membered (more preferably 5 - or 6-membered) heterogenities group containing 1-2 sulfur atom and 1 to 3 nitrogen atom, for example thiazolyl, isothiazolin, thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl and so on), dihydrothiazine etc.;

saturated 3 to 8-Clinica, for example diazolidinyl etc.;

unsaturated 3 to 8-membered (more preferably 5 - or 6 - techenie) heterogenities group containing 1-2 sulfur atom, such as thienyl, dehydrodidemnin, dehydrodidemnin etc.;

unsaturated condensed heterocyclic group containing 1-2 sulfur atom and 1 to 3 nitrogen atom, for example benzothiazolyl, benzothiadiazole etc.;

unsaturated 3 to 8-membered (more preferably 5 - or 6 - techenie) heterogenities group containing an oxygen atom, such as furyl, etc. ;

unsaturated 3 to 8-membered (more preferably 5 - or 6 - techenie) heterogenities group containing an oxygen atom and 1 to 2 sulfur atom, such as dihydroartemisinin etc.;

unsaturated condensed heterocyclic group containing 1-2 sulfur atom, for example benzothiazyl, benzodithiol etc.;

unsaturated condensed heterocyclic group containing an oxygen atom and 1 to 2 sulfur atom, such as benzoxanthene and so on, and similar groups.

Acyl fragment, as described above, can have 1 to 10 identical or different acceptable substituents such as lower alkyl, examples of which are given above, a lower alkoxy group, examples kotoisaa alkylamino, in which examples of the lower alkyl fragment described above, cyclo(lower)alkyl, examples of which are given above, cyclo(lower)alkenyl, examples of which are given above, halogen, amino, protected amino group, examples of which are given above, the hydroxy-group, a protected hydroxy-group, cyano, a nitro-group, carboxypropyl, protected carboxypropyl, alphagraph, sulfamoyl, aminogroup, oxoprop, amino(lower)alkyl, in which examples of the lower alkyl fragment described above, carbamoyloximes, hydroxy(lower) alkyl, for which examples of the lower alkyl fragment above, diamino(lower)alkylidene(such as diaminomethylene and so on), di(lower)alkylamino, for which examples of the lower alkyl fragment described above, di(lower)alkylamino(lower) alkyl, for which examples of the lower alkyl fragment described above, heterocycle(lower)alkyl, for which examples of the heterocyclic fragment and lower alkyl fragment above, or a similar group.

Suitable "aryl" and "aryl fragment" in the term "alloctype" may include phenyl, naphthyl, etc.

Acceptable "delete group" may include an acid residue, and lower ucati halogen, alloctype, for which examples of the acyl fragment above, or a similar group.

Suitable "halogen" and "halogen fragment" in the term "mono(di - or tri-) halo(lower)alkyl" may include fluorine, bromine, chlorine and iodine.

Suitable "protected carboxypropyl" and "protected carboximide" in terms of "protected carboxy(lower) alkoxygroup" and "protected carboxy(lower)alkenyl" may include protected in the usual way carboxypropyl etc.

Acceptable "in the usual way protected carboxypropyl" may include esterified carboxypropyl, etc., And suitable examples of such esters may include such esters as low alkalemia esters (e.g. methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, tert-butyl methyl ether, pentalogy ether, tert-pentalogy ether, hexyl ether, and so on); the lower alkenilovyh esters (e.g. vinyl ester, allyl ether, and so on); the lower alkinilovymi esters (for example, atinlay ether, propenyloxy ether and so on ); (lower)alkoxy(lower) alkalemia esters (for example, methoxymethyl ether, ethoxymethyl ether, isopropoxyphenyl is (for example, methylthiomethyl ether, ethyldimethylamine ether, ethylthioethyl ether, isopropylidenedioxy ether and so on); mono(di - or tri-) halo(lower) alkalemia esters (for example, 2 - itatiaia ether, 2,2,2-trichlorethylene ether and so on); (lower)- alkanoyloxy(lower)alkalemia esters (for example, acetoxymethyl ether, propionylacetate ether, butyrylacetate ether, veterinarinary ether, pivaloyloxymethyl ether, hexaniacinate ether, 1-ecotoxicology ether, 2-ecotoxicology ether, 2-propionylacetate ether and so on ), (lower)alkoxycarbonyl(lower)alkalemia esters (for example, methoxycarbonylmethyl ether, ethoxycarbonylmethylene ether, propoxycarbazone ether, 1-(or 2-)-[methoxycarbonyl] ethyl ester, 1-(or 2-)-[ethoxycarbonyl] ethyl ester, 1-(or 2-)-[propoxycarbonyl] - ethyl ester, 1-(or 2-)-[isopropoxycarbonyl] ethyl ester, and so on ); (lower)alkanesulfonyl(lower)alkalemia esters (for example, methylotrophy ether, 2-mutilative ether and so on); (lower) alkoxycarbonyl(lower)alkalemia esters (for example, methoxycarbonylmethyl ether, ethoxycarbonylmethylene ether, propoxycarbazone ether, tert-butok the ether, 1-(or 2-)-2 - isopropoxycarbonyloxymethyl ether and so on); thalidomide (lower)alkilany ester; (5-lower alkyl-2-oxo-1,3 - dioxol-4-yl)(lower)alkilany ester [for example, (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester, (5-ethyl-2-oxo - 1,3-dioxol-4-yl)methyl ester, (5-propyl-2-oxo-1,3-dioxol-4 - yl)ethyl ester, etc.]; mono(di - or tri-) aryl(lower) alkalemia esters, such as mono(di - or tri-)phenyl(lower)- alkalemia esters, which may have one or more suitable substituents (e.g., benzyl ester, 4-methoxybenzyloxy ether, 4-nitrobenzyloxy ether, finitely ether, trailovic ether, benzhydryl ester, bis (methoxyphenyl) methyl ester, 3,4-dimethoxybenzyl ether, 4-hydroxy-3,5-di-tert - butylbenzylamine ether and so on); arrouye esters, which may have one or more substituents such as substituted or unsubstituted phenyl esters (for example, phenyl ether, tallowy ether, tert-BUTYLPEROXY ether, Kilroy ether, mesityloxy ether, comenjoy ether, 4-hlorfenilovy ether, 4-methoxyphenacyl ether and so on); three(lower)alkylsilane esters; lower alkylthio (complex) ether (for example, methylthioethyl, ethylthioethyl and so on), etc.

Acceptable "GI "protected hydroxy(lower)alkyl" may include a conventional protective group, etc.

Acceptable "conventional protective group" may include acyl mentioned above, mono(di - or tri-)phenyl(lower)alkyl which may have one or more suitable substituents (e.g., benzyl, 4-methoxybenzyl, trityl and so on), tizamidine silyl, for example three(lower)alkylsilane (e.g., trimethylsilyl, tert - butyldimethylsilyl and so on) and so on, tetrahydropyranyl etc.

Suitable "heterocyclic group" and "heterocyclic fragment" in the term "heterocycle(lower)alkyl" may be listed on the example of the above heterocycles.

Acceptable "Deputy" in the definition of "heterocyclic group which may have an appropriate substituent(s)" may include lower alkyl, examples of which are given above, the lower alkoxygroup, examples of which are given above, lower alkenyl, examples of which are given above, the lower quinil, examples of which are given above, mono(di - or tri-) halo(lower)alkyl, for which examples of halogen and lower alkyl fragment above, cyclo(lower)alkyl, examples of which are given above, cyclo(lower)alkenyl, the examples given above, halogen, examples of which are given above, carboxypropyl, protected carboxypropyl, the reel, the examples given above, ar(lower)alkyl, for which examples of the aryl portion and the lower alkyl fragment above, carboxy(lower)alkyl, for which examples of the lower alkyl fragment above, protected carboxy (lower)alkyl, for which examples of protected carboxamidine and lower alkyl fragment above, the nitro-group, amino group, protected amino group, examples of which are given above, di(lower)alkylamino, for which examples of the lower alkyl fragment above, amino(lower)alkyl, for which examples of the lower alkyl fragment above, protected amino(lower)alkyl, for which examples of protected aminomalonate and lower alkyl fragment above, hydroxy(lower)alkyl, for which examples of the lower alkyl fragment above, protected hydroxy(lower)alkyl, for which examples of protected hydroxyflavone and lower alkyl fragment above, acyl, examples of which are given above, cyano, alphagraph, oxoprop, carbonarra, mercaptopropyl lowest allylthiourea, for which examples of the lower alkyl fragment above, aminogroup, Hydra is (lower)alkyl, for which examples of the lower alkoxyimino and lower alkyl fragment above, di(lower) alkylamino(lower)alkyl, for which examples of the lower alkyl fragment above, carboxy(lower)alkenyl, for which examples of the lowest alkenyl above, protected carboxy (lower)alkenyl, for which examples of protected carboxamidine and lower alkenylphenol fragment above, etc.

Acceptable substituent in the terms "aryl which may have one acceptable Deputy" may include lower alkyl, examples of which are given above, the lower alkoxygroup, examples of which are given above, lower alkenyl, examples of which are given above, the lower quinil, examples of which are given above, mono(di - or tri-) halo(lower)alkyl, for which examples of halogen and lower alkyl fragment above, cyclo(lower)alkyl, examples of which are given above, cyclo(lower)alkenyl, examples of which are given above, halogen, the examples given above, carboxypropyl, secure carboxypropyl, examples of which are given above, the hydroxy-group, a protected hydroxy-group, examples of which are given above, aryl, examples of which are given above, the Boxing(lower)alkyl, for which examples of the lower alkyl fragment above, protected carboxy(lower)alkyl, for which examples of protected carboxamidine and lower alkyl fragment above, the nitro-group, an amino group, a protected amino group, examples of which are given above, di(lower)alkylamino, for which examples of the lower alkyl fragment above, amino(lower)alkyl, for which examples of the lower alkyl fragment above, protected amino(lower)alkyl, for which examples of protected aminomalonate and lower alkyl fragment above, hydroxy(lower)alkyl, for which examples of the lower alkyl fragment above, protected hydroxy(lower)alkyl, for which examples of protected hydroxyflavone and lower alkyl fragment above, acyl, examples of which are given above, cyano, alphagroup, oxoprop, carbamoyloximes, mercaptopropyl, lower allylthiourea, for which examples of the lower alkyl fragment above, aminogroup etc.

Acceptable "Deputy" in the terms "heterocycle(lower)- alkyl, which may have an appropriate substituent(s)" may include lower alkyl, which is showing above lower quinil, examples of which are given above, mono(di - or tri-) halo(lower)alkyl, for which examples of halogen and lower alkyl fragment above, cyclo(lower)alkyl, examples of which are given above, cyclo (lower)alkenyl, examples of which are given above, halogen, examples of which are given above, carboxypropyl, secure carboxypropyl, examples of which are given above, the hydroxy-group, a protected hydroxy-group, examples of which are given above, aryl, examples of which are given above, ar(lower) alkyl, for which examples of the aryl portion and the lower alkyl fragment above, carboxy(lower)alkyl, for which examples of the lower alkyl fragment above, protected carboxy(lower)alkyl, for which examples of protected carboxamidine and lower alkyl fragment above, the nitro-group, an amino group, a protected amino group, examples of which are given above, di(lower)alkylamino, for which examples of the lower alkyl groups mentioned above, amino (lower)alkyl, for which examples of the lower alkyl fragment above, protected amino(lower)alkyl, for which examples of protected aminomalonate and lower alkyl s above protected hydroxy (lower)alkyl, for which examples of protected hydroxyflavone and lower alkyl fragment above, acyl, examples of which are given above, cyano, alphagroup, oxoprop, carbamoyloximes, mercaptopropyl, lower allylthiourea, for which examples of the lower alkyl fragment above, aminogroup etc.

Acceptable "adaderana carboxypropyl may include carbarnoyl, which may have one or two acceptable substituent, etc.

Acceptable "Deputy" in the expression "carbarnoyl, which may have one or two acceptable substituent" may include lower alkyl, examples of which are given above, the lower alkoxygroup, examples of which are given above, the lower allylthiourea, for which examples of the lower alkyl fragment above, the lower alkylamino, for which examples of the lower alkyl fragment above, cyclo(lower)alkyl, examples of which are given above, cyclo(lower)alkenyl, examples of which are given above, halogen, examples of which are given above, the amino group, a protected amino group, examples of which are given above, the hydroxy-group, a protected hydroxy-group, examples of which PNY above, alphagroup, sulfamoyl, aminogroup, oxoprop, amino(lower) alkyl, for which examples of the lower alkyl fragment above, carbamoyloximes, hydroxy(lower)alkyl, for which examples of the lower alkyl fragment above, diamino (lower)alkylidene(for example, diaminomethylene and so on), di(lower) alkylamino, for which examples of the lower alkyl fragment above, di(lower)alkylamino(lower)alkyl, for which examples of the lower alkyl fragment above, heterocycle (lower)alkyl, for which examples of the lower alkyl and heterocyclic fragment fragment above, etc.

Featured embodiment of the target compounds of formula (I) include the following compounds, in which:

Y is a group N or C - R1(in which R1represents hydrogen, (lower)alkyl, hydroxy-group, (lower)alkoxygroup, hydroxy(lower)alkyl, acylamino(lower)alkyl (more preferably (lower) alkanolamine(lower)alkyl), carboxy(lower)alkoxygroup, hydroxy(lower)alkoxygroup, phenyl, piperidyl or pyrrolyl);

R2represents hydrogen, naphthyl, phenyl which may have one acceptable substituent (preferably seagrape and a protected amino group (most preferably trihalogen(lower)alkylsulfonamides), fenoxaprop, trihalogen(lower)alkyl, aroyl (preferably benzoyl), pyrrolyl, tetrazolyl, pyrazolyl, thienyl, furyl, thiazolyl, pyridyl or pyrimidinyl, each of which may have one to three suitable substituents (more preferably Deputy selected from the group comprising: carboxypropyl, secure carboxypropyl (more preferably esterified carboxylate, most preferably diphenyl(lower)alkoxycarbonyl), acyl (more preferably lower alkanoyl or carbarnoyl), lower alkyl, halogen, hydroxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, amino, protected amino (more preferably alluminare), carboxy(lower)alkenyl, protected carboxy (lower)alkenyl (more preferably esterified carboxy (lower)alkenyl, most preferably(lower)alkoxycarbonyl (lower)alkenyl), carboxy(lower)alkyl [more preferably pyrrolyl, which may have one to three substituents selected from the group comprising: carboxypropyl, (lower)alkanoyl, carbarnoyl, (lower)alkyl, halogen, hydroxyimino(lower)alkyl,(lower)alkoxyimino (lower)alkyl, di(lower)alkylamino(lower (more preferably pyrrolyl, carboxypropyl, lower alcanoterreos, carbamoylethyl, mono(di) (lower)acylpyrrole, hydroxyimino(lower)acylpyrrole, (lower)alkoxyimino(lower)acylpyrrole, [di(lower)alkyl - amino(lower))acylpyrrole, cyanopropyl, carboxy(lower)- alkenylboronic, (lower)alkoxycarbonyl(lower) alkenylboronic, carboxy(lower)acylpyrrole, dialogerror, pyrrolyl, substituted(lower) alkyl and cyano, pyrrolyl, substituted di(lower)alkylamino(lower) alkyl and cyano, pyrrolyl, replaced two (lower) alkilani and cyano), tetrazolyl, pyrazolyl, possibly substituted amino group, Tinel, possibly substituted by cyano, furyl, possibly substituted by cyano, thiazolyl, pyridyl or pyrimidinyl] or pyrrolyl(lower)alkyl;

R3represents hydrogen, lower alkoxygroup, the hydroxy-group, or pyrrolyl, or

R2and R3are connected to each other to form divalent radical of the formula:

< / BR>
in which R5is hydrogen or lower alkyl, R6is hydrogen or lower alkyl and R11is hydrogen or cyano;

Z - band N or C - R4(in which R4represents hydrogen, halogen, hydroxy(lower)alkyl, sinograin(lower)alkylidene, di(lower) alkylamino(lower)alkyl and heterocycle(lower)alkyl (more preferably morpholinyl(lower)alkyl, more preferably diamino(lower)alkylaminocarbonyl, di(lower)alkylamino (lower)allylcarbamate or morpholinyl(lower)allylcarbamate); and

W - band N or C - R12in which R12represents hydrogen;

Preferred variants of the target compounds of formula (I) represented by the following General formulas (A) - (C):

< / BR>
in which R2represents hydrogen, naphthyl, phenyl which may have one acceptable substituent (preferably Deputy selected from the group comprising trihalogen(lower)alkyl, cyano, lower alkyl, halogen, the nitro-group and a protected amino group (most preferably trihalogen(lower)alkylsulfonamides) [more preferably phenyl, trihalogen(lower)alkylphenyl, cyanophenyl, (lower) alkylphenyl, halogenfree, nitrophenyl, trihalogen(lower) alkylsulfonamides or naphthyl], fenoxaprop, trihalogen (lower)alkyl, aroyl (preferably benzoyl), pyrrolyl, tetrazolyl, pyrazolyl, thienyl, furyl, thiazolyl, pyridyl or pyrimidinyl, each of which may have 1-3 acceptable Deputy is positive lower alkanol or carbarnoyl) (lower)alkyl, halogen, hydroxyimino(lower)alkyl, di(lower) alkylamino(lower)alkyl, cyano, amino group, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl (more preferably esterified carboxy(lower)alkenyl, most preferably(lower) alkoxycarbonyl(lower)alkenyl) carboxy(lower)alkyl (more preferably pyrrolyl, which may have 1-3 substituent selected from the group comprising: carboxypropyl, (lower)alkanoyl, carbarnoyl, (lower)alkyl, halogen, hydroxyimino(lower)alkyl, (lower)alkoxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, carboxy (lower)alkenyl, (lower)alkoxycarbonyl(lower)alkenyl and carboxy(lower)alkyl (more preferably pyrrolyl, carboxypropyl, (lower)alcanoterreos, carbamoylethyl, mono(or di) (lower)acylpyrrole, hydroxyimino(lower)acylpyrrole, (lower)alkoxyimino(lower)acylpyrrole, [di(lower)alkylamino(lowest)] acylpyrrole, cyanopropyl, carboxy(lower)alkenylboronic, (lower) alkoxycarbonyl(lower)alkenylboronic, carboxy(lower) acylpyrrole, dialogerror, pyrrolyl, substituted(lower) alkyl and cyano, pyrrolyl, substituted di(lower)alkylamino(lower) ozmone substituted amino group, thienyl, possibly substituted by cyano, furyl, possibly substituted by cyano, thiazolyl, pyridyl or pyrimidinyl] or pyrrolyl (lower)alkyl, and

R4represents hydrogen, halogen, hydroxy(lower)alkyl, cyano; pyrrolyl, tetrazolyl, carbarnoyl, which may have one Deputy selected from the group comprising: diamino(lower)alkylidene, di(lower)alkylamino(lower) alkyl and heterocycle(lower)alkyl (more preferably morpholinyl (lower)alkyl) [more preferably diamino(lower)alkylaminocarbonyl, di(lower)alkylamino (lower)allylcarbamate, morpholinyl(lower)allylcarbamate];

< / BR>
in which R1represents hydrogen, (lower)alkyl, hydroxy-group, (lower)alkoxygroup, hydroxy(lower)alkyl, acylamino(lower)alkyl (more preferably(lower) alkanolamine(lower)alkyl), carboxy(lower) alkoxygroup, hydroxy(lower) alkoxygroup, phenyl, piperidyl or pyrrolyl;

R2represents hydrogen, naphthyl, phenyl which may have one acceptable substituent (preferably Deputy selected from the group comprising: trihalogen(lower)alkyl, cyano, (lower)alkyl, halogen, the nitro-group and a protected amino group (most pre is alkylphenyl, cyanophenyl, (lower) alkylphenyl, halogenfree, nitrophenyl, trihalogen(lower) alkylsulfonamides or naphthyl], fenoxaprop, trihalogen-(lower)alkyl, aroyl, (more preferably benzopyrrole, tetrazolyl, pyrazolyl, thienyl, furyl, thiazolyl, pyridyl or pyrimidinyl, each of which may have 1-3 acceptable substituents (more preferably Deputy selected from the group comprising: carboxypropyl, acyl (more preferably alkanoyl or carbarnoyl), (lower) alkyl, halogen, hydroxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, amino group, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl (more preferably esterified carboxy(lower)alkenyl, most preferably(lower)alkoxycarbonyl(lower) alkenyl), carboxy(lower)alkyl [more preferably pyrrolyl, which may have 1-3 substituent selected from the group comprising: carboxypropyl, (lower)alkanoyl, carbarnoyl, (lower)alkyl, halogen, hydroxyimino(lower)alkyl, (lower)alkoxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, carboxy(lower) alkenyl, (lower)alkoxycarbonyl(lower)alkenyl and carboxy (lower)alkyl (more preferably, hydroxyimino(lower)acylpyrrole, (lower)alkoxyimino(lower)acylpyrrole, [di(lower) alkylamino(lower)acylpyrrole, cyanopropyl, carboxy(lower) alkenylboronic, (lower)alkoxycarbonyl(lower)alkenylboronic, carboxy(lower)acylpyrrole, dialogerror, pyrrolyl, substituted (lower)alkyl and cyano, pyrrolyl, substituted di(lower)alkylamino(lower) alkyl and cyano, pyrrolyl, replaced the two (lower) alkilani and cyano), tetrazolyl, pyrazolyl, possibly substituted amino group, thienyl, possibly substituted by cyano, furyl, possibly substituted by cyano, thiazolyl, pyridyl or pyrimidinyl] or pyrrolyl(lower)alkyl; and

< / BR>
in which R5is hydrogen or lower alkyl, R6is hydrogen or lower alkyl, and R11is hydrogen or cyano.

Methods of obtaining the target and source connections of the present invention is explained in detail below.

Method (1)

The compound of formula (I) or its salt can be obtained by reaction of compounds of formula (II) or its reactive derivative at carboxypropyl, or its salt with the compound of the formula (III) or its reactive derivative at aminogroup, or its salt.

Acceptable reactionsto the reaction of compounds of formula (III) with a strong derivative, for example, bis(trimethylsilyl)acetamide", she mono(trimethylsilyl)ndimethylacetamide (for example, N-(trimethylsilyl)ndimethylacetamide), bis(trimethylsilyl(urea, etc., a derivative formed by reaction of the compound of formula (III) with phosphorus trichloride or phosgene, etc.

Acceptable reactive derivative at carboxypropyl the compounds of formula (II) may include conventional derivatives, such as acid halides, acid anhydrides, activated amides, activated esters, etc.,

Acceptable examples of the reactive derivatives may include the acid chloride of the acid, acid azide, mixed anhydride with an acid such as substituted phosphoric acid (e.g., dialkylphosphorous acid, phenylphosphine acid, diphenylphosphoryl acid, dibenzylamine acid, halogenated phosphoric acid, and so on), dialkylphosphorous acid, sulfurous acid, tisera acid, sulfuric acid, acid (for example, methanesulfonate acid and so on), aliphatic carboxylic acid (e.g. acetic acid, propionic acid, butyric acid, somalina acid, iwalewa acid, valeric acid, isovalerianic acid, 2-ethylmalonate acid, trichloronat drid acid, amide, activated imidazole, 1-hydroxy-1H-benzotriazole, 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole, or activated ester (for example, cinematology ether, methyl ether, ethyl ether, methoxymethyl ether, dimethylaminomethylene ether), [(CH3)2-N+=CH-] ester, vinyl ester, propargilovyh ether, p-nitrophenyloctyl ether, 2,4-dinitrophenoxy ether, trichloranisole ether, pentachlorphenol ether, methylphenylene ether, phenylazophenyl ester, a phenyl thioether, p-nitrophenyloctyl tiefer, p-crazily tiefer, benzothiazolinone tiefer, carboxymethoxy tiefer, paranjoy ether, pyridyloxy ether, piperidinyl ether, 8-hinolinovy tiefer and so on) or an ester with N-hydroxy (for example, N,N-dimethylhydroxylamine, 1-hydroxy-2(1H)-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole and so on), etc., These reactive derivatives can be selected depending on the type of compounds of formula (II), scheduled for use.

The reaction is usually carried out in a conventional solvent such as water, alcohol (e.g. methanol, ethanol and so on ), acetone, dioxane, acetonitrile, chloroform, chlorine is in the solvent, no adverse effects on the course of the reaction. Listed ordinary solvents can also be used in mixture with water.

In this reaction, when the compound of the formula (II) used in the form of the free acid or a salt thereof, the reaction being recommended in the presence of a conventional condensing means, for example N,N-dicyclohexylcarbodiimide, N-cyclohexyl-N'- morpholinobutyrophenone, N-cyclohexyl-N'-(4-diethylaminoethoxy)carbodiimide, N, N'-diethylcarbamazine, - -diisopropylcarbodiimide, N-ethyl-N'- (3-diethylaminopropyl)carbodiimide, N-N'-carbonylbis(2-methylimidazole), pentamethylene-cyclohexylamine, diphenylethan-N-cyclohexylamine, ethoxyacetylene, 1-alkoxy-1-chloroethylene, trialkylphosphites, ethyloleate, isopropylpalmitate, phosphorus oxychloride (phosphorylchloride), phosphorus trichloride, thionyl chloride, oxalicacid, (lower)alkylhalogenide [for example, ethylchloride, isopropylcarbamate etc.], triphenylphosphine, salts of 2-ethyl-7-hydroxybenzotriazole, intramolecular salt hydroxide 2-ethyl-5-(m-sulfophenyl)isoxazole, complex N-(lower)alkylalkenylcyclopropanes (for example, 1-methyl-2-chloropyrimidine and so on) with three(lower)alkylamino (such as the EPA, obtained by the reaction of N,N-dimethylformamide c thionyl chloride, phosgene, trichloromethylcarbonate, phosphorus oxychloride, etc. or similar condensing means.

The reaction can also be carried out in the presence of inorganic or organic bases, for example, bicarbonate of an alkali metal, three(lower)alkylamine (e.g. triethylamine, etc. ), pyridine, N-(lower)alkylphosphine, N-N-di(lower)alkylenediamine, lower alkoxide of an alkali metal (e.g. sodium methoxide, and so on), etc.

The reaction temperature is not crucial, and usually the reaction is carried out under conditions of from cooling to heating.

Method (A).

The compound of formula (IIa) or its salt can be prepared by the reaction of the compound of formula (IV) or its salt with the compound of the formula (V) or its salt.

The above reaction is usually carried out in a solvent such as water, alcohol (e.g. methanol, ethanol and so on), benzene, N,N-dimethylformamide, tetrahydrofuran, toluene, methylene chloride, ethylene chloride, chloroform, dioxane, diethyl ether or any other solvent not affecting the reaction adverse effects. These solvents can also primeneniia from weak to strong heating.

The reaction is usually carried out in the presence of an acid including Lewis acid.

Acceptable acid may include an organic acid (e.g. formic acid, acetic acid, propionic acid, trichloroacetic acid, triperoxonane acid and so on) and inorganic acid (e.g. hydrochloric acid, Hydrobromic acid, sulfuric acid, hydrogen chloride, hydrogen bromide, zinc halide (e.g. zinc chloride, zinc bromide, and so on), and so on), etc.

If the acid and/or the original connection are in the liquid state, they can be used also as a solvent.

Method (B)

The compound of formula (IIc) or its salt can be obtained by treating compounds of formula (IIb) or its salt under the reaction conditions elimination carboxy-protective group.

This reaction can be carried out according to methodology described in preparative example 56, or in the same way.

Method (B)

The compound of formula (IId) or its salt can be obtained by reduction of compounds of formula (IIC) or its salt.

This reaction can be carried out according to methodology described in preparative example 52, or analogovaya (IIa) or its salt with the compound of the formula (IV) or its salt.

The reaction can be carried out according to methodology described in preparative examples 37 and 38, or in the same way.

Method (D)

The compound of formula (II) or its salt can be obtained by treating compounds of formula (IIf) or its salt under the reaction conditions elimination carboxy-protective group.

This reaction can be carried out according to methodology described in preparative example 45, or in the same way.

Method (E)

The compound of formula (IIh) or its salt can be prepared by the reaction of the compound of formula (IIg) or its salt with the compound of the formula (VII) or its salt.

The reaction can be carried out according to methodology described in preparative examples 32 and 34, or in the same way.

Method (F)

The compound of formula (IIr) or its salt can be prepared by the reaction of the compound of formula (VIII) or its salt with the compound of the formula (IX) or its salt.

The reaction can be carried out according to methodology described in preparative example 26, or a similar method.

Method (F)

The compound of formula (IIi) or its salt can be obtained by treating compounds of formula (IIr) or its salt under the reaction conditions of cyanoguanidine.

The reaction moposal (G)

The compound of formula (IIj) or its salt can be obtained by treating compounds of formula (IIc) or its reactive derivative at carboxypropyl, or its salt in the conditions of the amidation reaction.

Acceptable lidiruyushchim reagent intended for use in the amidation reaction is a compound of the formula

H-R15< / BR>
where R15takes values above, or its reactive derivative, or its salt, etc.

Acceptable reactive derivative of the compound of formula (X) may include Schiff's base type aminogroup or its tautomeric isomer type of enamine formed by reaction of the compound of formula (X) with a carbonyl compound such as aldehyde, ketone and so on; silyl derivative such as bis(trimethylsilyl)ndimethylacetamide, mono(trimethylsilyl)ndimethylacetamide/(for example, N-(trimethylsilyl)ndimethylacetamide/, bis(trimethylsilyl)urea, etc.; a derivative formed by reaction of the compound of formula (X) with phosphorus trichloride, with phosgene, etc.

Acceptable reactive derivative of the carboxy group of the compounds of formula (IIc) may include gelegenheid acid, acid anhydride, activated amide, aktivirovat, azide acid, a mixed acid anhydride with an acid such as substituted phosphoric acid (e.g., dialkylphosphorous acid, phenylphosphinic acid, diphenylphosphinic acid, dibenzylamino acid, halogenated phosphoric acid, and so on), dialkylphosphorous acid, sulfurous acid, tournoi acid, sulfuric acid, sulfonic acid (e.g., methanesulfonic acid and so on), aliphatic carboxylic acid (e.g. acetic acid, propionic acid, butyric acid, somaclonal acid, Pikalevo acid, valerianic acid, isovalerianic acid, 2-ethylmalonic acid, trichloroacetic acid, and so on) or aromatic carboxylic acid (e.g. benzoic acid, etc), symmetrical anhydride, activated amide with imidazole, 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole, or activated ester (for example, cinematology ether, methoxymethyl ether, dimethylaminomethylene ether [(CH3)2N+=CH-] ester, vinyl ester, ethyl ester, propargilovyh ether, p-nitrophenyloctyl ether, 2,4-dinitrophenoxy ether, trichloranisole ether, pentachlorphenol ether, methylphenylene ether, phenylazo pyranyloxy ether, pyridyloxy ether, piperidinyl ether, 8-hinolinovy tiefer and so on ) or an ester with N-hydroxy (for example, N,N-dimethylhydroxylamine, 1-hydroxy-2(1H)-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole and so on), etc., These reactive derivatives may be selected based on the type intended for use of the compounds of formula (IIc).

The reaction is usually carried out in a conventional solvent such as water, alcohol (e.g. methanol, ethanol and so on), acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, toluene, ethyl acetate, N,N-dimethylformamide, pyridine or any other organic solvent that does not adversely impact on the course of the reaction. Such conventional solvents can also be used in mixture with water. If the base and/or the original connection is in a liquid state, they can also be used as solvent.

In this reaction, when the compound of the formula (II) used in the form of the free acid or a salt thereof, the reaction being recommended in the presence of a conventional condensing means, for example N,N'-dicyclohexylcarbodiimide is ethylcarbodiimide, N,N'-diisopropylcarbodiimide, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide, N,N'-carbonylbis(2-methylimidazole), pentamethylene-N-cyclohexylamine, diphenylmethan-N-cyclohexylamine, ethoxyacetylene, 1-alkoxy-1-chloroethylene, trialkylphosphites, ethyloleate, isopropylpalmitate, phosphorus oxychloride (phosphorylchloride), phosphorus trichloride, thionyl chloride, oxalicacid, (lower)alkylhalogenide (for example, ethylchloride, isopropylcarbamate and so on), triphenylphosphine, salts of 2-ethyl-7-hydroxybenzotriazole, intramolecular salt hydroxide 2-ethyl-5-(m-sulfophenyl)isoxazole, 1-(p-chlorobenzenesulfonate)-6-chloro-1H-benzotriazole, the so-called reagent, Vilsmeier obtained by the reaction of N, N-dimethylformamide with thionyl chloride, phosgene, trichloromethylcarbonate, phosphorus oxychloride, etc. etc.

The reaction can also be carried out in the presence of inorganic or organic bases such as bicarbonate of an alkali metal, three (lower) alkylamine, pyridine, N-(lower )alkylphosphine, N,N-di(lower)alkylenediamine etc.

The reaction temperature is not crucial, and the reaction is usually carried out under conditions of from cooling to heating.

Method (H)

With the x reaction formirovaniya.

The reaction can be carried out according to methodology described in preparative example 118, or in the same way.

Way (N)

The compound of formula (IIm) or its salt can be obtained by reduction of compounds of formula (IIb) or its salt.

The recovery may be carried out according to methodology described in preparative example 119, or in the same way.

Method (I)

The compound of formula (II ° series) or its salt can be obtained by cyclization of the compounds of formula (IIn) or its salt.

The cyclization can be carried out according to methodology described in preparative example 120, or in the same way.

Method (J)

Connection (IIq) or its salt can be obtained by treating compounds of formula (IIp) or its salt under the reaction conditions of cyanoguanidine.

The reaction can be conducted according to procedures described in preparative examples 37 and 38, or similar methods.

With regard to acceptable salts of the source and target compounds and their reactive derivatives in the methods (I) and (A)-(J), as examples one can point to salt indicated for compounds of formula (I).

The new guanidine derivatives of the formula (I) and their pharmaceutical>/H+- metabolism in the cells, which are applicable as inhibitors of the cellular Na+/H+exchange.

Accordingly, the new guanidine derivatives of the formula (I) and their pharmaceutically acceptable salts can be used for the treatment and/or prevention of cardiovascular diseases (e.g. hypertension, angina, myocardial infarction, heart failure (e.g. congestive heart failure, acute heart failure, hypertrophy of the heart, and so on ), arrhythmia (e.g. ischemic arrhythmia, arrhythmia due to myocardial infarction, arrhythmia after RTSA or after thrombolite and so on), restenosis after RTSA and so on ), vascular diseases of the brain (e.g., attack, ischemia, episodes of bleeding, and so on), renal diseases (e.g., diabetic nephropathy, ischemic acute renal failure and so on), arteriosclerosis, shock (e.g., associated with bleeding shock caused by endotoxin shock, and so on), etc., and can also be used as a means of myocardial protection, protection of organs for organ transplant, when open-heart surgery, etc.

To show the applicability of the guanidine derivatives of the formula (X) and their predstavitelej guanidine derivative of the formula (I) as the test compound, illustrated as follows.

I Tested the connection

(a) 2-/3-Methylsulphonyl-5-(pyrrol-1-yl)benzoyl/guanidine

/2/ Inhibiting activity aimed at the cellular Na+/H+-exchange

/i/ test Method

The methodology used is similar to the methodology described in: Enzymology 173, 777 (1989).

Cellular preparation. One male line SD weighing 250-300 g hammer blow on the head. Then the remote thymus transferred into a cooled ice environment with NaCl (140 mm sodium chloride, 1 mm potassium chloride, 1 mm calcium chloride, 1 mm magnesium chloride, 10 mm glucose and 20 mm N-2-hydroxyethylpiperazine-N'-2-econsultancy acid (HEPES), pH 7.3), cut into small pieces and transferred to a glass homogenizer. The cells divide careful strokes and the resulting suspension is filtered through six layers of surgical gauze, and the filtrate centrifuged 5 minutes at 4oC and 1000g. The precipitate is again suspended in RPMI 1640 medium (pH 7.3) at room temperature with the establishment of a final cell concentration of 1 to 107cells/ml.

Analysis. This method reveals the swelling that accompanies the activation of substances that contribute Na+/H+the metabolism in the cells, inkubiruemykh with sodium propionate. Propiona acidification and, as a consequence, the activation of Na+/H+-exchange, where the exchange of extracellular Na+on cytoplasmically N+. The absorption of osmotically captured water is manifested in cellular swelling.

The size of cells and their number is determined on the appliance, Coulter Counter-Channelizer (at-11). The solution of thymocytes (0.1 ml) are suspended in 20 ml of nitropropionate medium (140 mm sodium propionate, 1 mm potassium chloride, 1 mm calcium chloride, 1 mm magnesium chloride, 10 mm glucose, 20 mm N-2-hydroxyethylpiperazine- -N'-2-econsultancy acid (HEPES), pH 6.8) with the addition of the test compounds dissolved in dimethyl sulfoxide (final concentration of DMSO of 0.1%). Within 4 minutes the increase in cells induced Na+/H+the exchange retains the linear and the swelling eventually see every minute after the addition of thymocytes. The rate of swelling (volume/min) is determined by using 3-5 concentrations of the test compounds. Then use a line graph burka calculate the apparent magnitudeand.

/3/ the results of the tests

< / BR>
The target compounds of formula (I) or their pharmaceutically acceptable salts are usually introduced mammals, including Chi is, microcapsules, tablets, granules, powders, lozenges, syrups, aerosols, inhalation, suspensions, emulsions, and so on), injectively dosage forms, suppositories, ointments, etc.

Dosage forms of this invention can contain various organic or inorganic carriers, commonly used for pharmaceutical purposes, such as fillers (for example, sucrose, starch, mannitol, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, calcium carbonate, and so on), binder (e.g., cellulose, methylcellulose, hydroxypropylcellulose, polipropilenglicol, gelatin, gum Arabic, polyethyleneglycol, sucrose, starch and so on), strukturator (for example, starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, hydroxypropylmethyl, nitroglycol starch, sodium bicarbonate, calcium phosphate, calcium citrate and so on), a lubricant (e.g. magnesium stearate, talc, sodium lauryl sulfate, and so on), corrigent (for example, citric acid, menthol, glycine, orange powder, and so on ), preservatives (e.g. sodium benzoate, sodium bisulfite, methylparaben, propylparaben, and so on), a stabilizer (for example, citric acid, sodium citrate, acetic acid and so on), suspendisse environments the e thinners (for example, water, and so on), wax base (e.g. cocoa butter, polyethylene glycol, white petrolatum, and so on).

The active ingredient is usually administered in unit dosage form in an amount of 0.01-500 mg/kg 1-4 times a day. However, this dosage may be increased or decreased depending on the age, weight, condition of the patient or the method of administration.

The following preparative examples and examples are given to more detailed illustration of the present invention.

Preparative example 1.

To a mixture of concentrated sulfuric acid (53.3 per ml) and conc. nitric acid (36 ml) for 10 minutes at 20o-30oC added dropwise a solution of 4-chloro-3-methylsulfonylbenzoyl acid (22,5 g) in conc. sulfuric acid (135 ml) and the mixture is stirred for 5 hours at 75-80oC. After cooling with ice, the mixture is transferred into ice-cold water and the precipitate filtered off to obtain 4-chloro-3-methylsulphonyl-5-nitrobenzoic acid (24,85 g).

So pl. 196oC.

IR (nujol): 1690, 1535, 1320, 1140 cm-1.

NMR (DMSO-d6) : to 3.52 (3H,s), 8,69 (1H, d, J=2 Hz), and 8.8 (1H, d, J=2 Hz), 14,25 (1, sh.C).

Preparative example 2.

A mixture of 4-chloro-3-methylsulphonyl-5-nitrobenzoic acids is Aut water and adding potassium carbonate in a mixture of set pH 8. The mixture is extracted with a mixture of ethyl acetate with tetrahydrofuran. The extract was washed with brine, dried over magnesium sulfate and evaporated in vacuum. Rinse residue diisopropyl ether get methyl ether 4-chloro-3-methylsulphonyl-5-nitrobenzoic acid (10,23 g).

So pl. 168o-169o.

IR (nujol): 1730, 1605, 1525, 1360, 1315, 1140 cm-1.

NMR (DMSO-d6) to 3.52 (3H,s), of 3.96 (3H,s), 8,68 (1H, d, J=2 Hz), cent to 8.85 (1H, d, J = 2 Hz).

Preparative example 3.

By the method similar to the method of preparative example 2, obtained the following compound: methyl ester of 3-methylsulphonyl-5-nitro-4-piperidinemethanol acid.

So pl. 147o-150o.

IR (nujol): 1720, 1600, 1525, 1360, 1140 cm-1.

NMR (DMSO-d6) : : 1,48-1,72 (6H, m), 3-3,12 (4H, m), of 3.45 (3H, s) to 3.92 (3H, s), 8,54 (1H, d, J=2.2 Hz), 8,64 (1H, a, J =2.2 Hz).

Preparative example 4.

To a mixture of methyl ester 4-chloro-3-methylsulphonyl-5-nitrobenzoic acid (9.5 g) and triethylamine (5 ml) in methanol (150 ml) and tetrahydrofuran (100 ml) is added 10% palladium on coal (2.5 g) and the mixture is subjected to catalytic recovery at room temperature and atmospheric pressure. The catalyst is filtered off and the filtrate ispara the Oia set pH 9. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuum. Rinse residue diisopropyl ether obtain methyl ester of 5-amino-3-methylsulfonylbenzoyl acid (5,85 g).

So pl. 181-183oC.

IR (nujol): 3480, 3440, 3370, 1725, 1605, 1330, 1150 cm-1.

NMR (DMSO-d6) : : 3,17 (3H, S), 3,86 (3H, s), 6,03 (2H, s), 7,28 - to 7.32 (1H, m), 7,43-of 7.48 (1H, m), of 7.48-rate of 7.54 (1H, m).

Preparative example 5.

A mixture of methyl ester of 5-amino-3-methylsulfonylbenzoyl acid (1.5 g) and 2,5-dimethoxytetrahydrofuran (1.3 ml) in acetic acid (4.5 ml) is boiled with stirring for 2 hours. After cooling, the mixture is transferred into a water-ethyl acetate and addition of 20% aqueous potassium carbonate solution set pH 8. The separated organic layer was washed with brine and dried over magnesium sulfate. The solvent is removed by concentration and rinsing residue diisopropyl ether obtain methyl ester of 3-methylsulphonyl-5-(pyrrol-1-yl)benzoic acid (1,58 g).

So pl. 117-121o.

IR (nujol): 1720, 1605, 1310, 1150 cm-1.

NMR (DMSO-d6) : : 3,39 (3H, s), of 3.95 (3H, s), 6,37 (2H, s), a 7.62 (2H, S), 8,23 (1H, S), 8,35 (2H, S).

Preparative example 6.

On Mitteilungen-4-piperidino-5-(pyrrol-1-yl)benzoic acid

So pl. 175-176oC.

IR (nujol): 1720, 1605, 1340, 1145 cm-1.

NMR (DMSO-d6) : : 1,18 of 1.7 (6H, m), 2,3-3,1 (4H, m), 3,44 (4H, s) to 3.89 (3H, s), 6,26-6,33 (2H, m), 6,95-7,02 (2H, m), to 7.93 (1H, H, J = 2.2 Hz), 8,55 (1H, d, J = 2.2 Hz).

(2) Ethyl ester of 3-(pyrrol-1-yl)benzoic acid

So pl. 46-48oC.

IR (nujol): 1710, 1590 cm-1.

NMR (DMSO-d6) : of 1.35 (3H, t, J=7,1 Hz), 4,36 (2H, K, J = 7,1 Hz), 6,26-6,37 (2H, m), 7,37 is 7.5 (2H, m), to 7.61 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,83 (1H, d, J = 7.8 Hz), 7,87 (1H, d, 7-7,8 Hz), 8,03 (1H, s).

Elemental analysis for C13H13NO2:

Calculated: C 72,54, H 6,09, N 6,51

Found: C 72,42, H 6,21, N 6,56

(3) Methyl ester 3-(pyrrol-1-yl)benzoic acid

IR (film); 1720, 1590 cm-1.

NMR (DMSO-d6) : : 3-91 (3H, S), 6,3-6,38 (2H, m), 7,4-of 7.48 (2H, m), to 7.59 (1H, DD, J = 7.9 Hz), 7.9 Hz), 7,8-7,92 (2H, m), with 8.05 (1H, DD, J = 1.9 Hz, 1.9 Hz).

(4) Ethyl ester of 2-(pyrrol-1-yl)benzoic acid

IR (nujol): 1710, 1600 cm-1.

NMR (DMSO-d6) : : of 1.06 (3H, t, J=7.1 Ha), 4.09 to (2H, K, 7-7,1 Hz), is 6.19-6,27 (2H, m), 6,86-6,93 (2H, m), 7,42-7,53 (2H, m), of 7.64 (1H, DD, J=1.7 Hz, 7.2 Hz), 7,69-to 7.77 (1H, m).

(5) Methyl ester of 3,5-di(pyrrol-1-yl)benzoic acid

So pl. 111-113oC.

IR (nujol): 1720, 1600 cm-1.

NMR (DMSO-d6) : to 3.92 (3H, s), 6,28-6,4 (4H, m), 7,55-to 7.67 (4H, m)BR> Calculated; C 72,17, 5,30 H, N 10,52

Found: C 72,31, H 5,28, N 10,44

(6) Methyl ester of 3-nitro-5-(pyrrol-1-yl)benzoic acid

So pl. 147-148oC.

IR (nujol): 1720, 1540, 1360, 1340, 1260, 740, 730 cm-1.

NMR (DMSO-d6) : : of 3.96 (3H, s), 6,36-6,4 (2H, m), and 7.6 to 7.7 (2H, m), and 8.4 to 8.5 (2H, m), 7,6-8,65 (1H, m).

MASS (m/z) : 246 (M+)

Elemental analysis for C12H10N2O4< / BR>
Calculated: C 58,53, H 4.09 to, N 11,30

Found; C 58,63, H was 4.02, N 11,29

(7) Dimethyl 5-(pyrrol-1-yl)isophthalic acid

So pl. 108-109oC.

IR (nujol): 3125, 1720, 1605, 1235 cm-1.

NMR (DMSO-d6) : to 3.92 (6H, s), 6,32 to 6.35 (2H, m), 7,49-7,52 (2H, m), 8,23-of 8.27 (3H, m)

MASS (m/z): 260 (M++ 1).

Elemental analysis for C14H13NO4< / BR>
Calculated: C 64,85, H of 5.05, N 5,40

Found: C 64,96, H 5,15, N 5,44

(8) Methyl ether 2-methoxy-5-methylsulphonyl-3-(pyrrol-1-yl)benzoic acid

So pl. 97-98oC.

IR (nujol): 1720, 1150, 1080, 750 cm-1.

NMR (DMSO-d6) : to 3.34 (3H, s), 3,49 (3H, s), 3,91 (3H, s), 6,32 to 6.35 (2H, m), 7,15 - 7,22 (2H, m), 8,08 (1H, d, J = 2,4 Hz).

Preparative example 7.

To a mixture of methyl ester of 3-methylsulphonyl-5-nitro-4-piperidinemethanol acid (5.6 g) with methanol (50 ml) and tetrahydrofuran temperature and atmospheric pressure. The catalyst is filtered off and the filtrate evaporated in vacuum. Rinse residue with a mixture of diisopropyl ether and n-hexane receive the methyl ester of 5-amino-3-methylsulphonyl-4-piperidinemethanol acid (4,88 g).

So pl. 178-179oC.

IR (nujol): 3350, 3250, 1710, 1330, 1130 cm-1.

NMR (DMSO-d6) : of 1.35 to 1.8 (6H, m), 2,74 - 3,91 (2H, m), 3,28 - of 3.46 (2H, m) to 3.35 (3H, s), of 3.84 (3H, s), 7,46 (1H, d, J = 2.1 Hz), a 7.62 (1H, d, J = 2.1 Hz).

Preparative example 8.

A mixture of 4-chloro-3-methylsulphonyl-5-nitrobenzoic acid (5 g) and piperidine (25 ml) is stirred for 1 hour at room temperature. To the mixture are added ethyl acetate and water added conc. hydrochloric acid in a mixture of set pH 1. The separated organic layer is washed with water and dried over magnesium sulfate. The solvent is removed by concentration and rinsing the residue with a mixture of diisopropyl ether and n-hexane get 3-methylsulphonyl-5-nitro-4-piperidinemethanol acid (5,66 g).

So pl. 197-199oC.

IR (nujol): 1700, 1530, 1305, 1125 cm-1.

NMR (DMSO-d6) : 1,47-of 1.74 (6H, m), 3,01 - 3,13 (4H, m), of 3.45 (3H, s), 8,48 (1H, d, J = 2.1 Hz), 8,65 (1H, d, J = 2.1 Hz), 13,91 (1H, sh.C).

Preparative example 9.

A mixture of ethyl ester of 3-aminobenzo is 0-70oC. To the reaction mixture are added water and adding potassium carbonate establish a pH of 8. The formed precipitate is filtered off and the residue dissolved in a mixture of ethyl acetate with tetrahydrofuran. The mixture is washed with water, dried over magnesium sulfate and evaporated in vacuum. By recrystallization of the residue from a mixture of ethanol with diisopropyl ether get the ethyl ester of 3-(1H-tetrazol-1-yl)benzoic acid (2,44 G).

So pl. 104-105oC.

IR (nujol): 3120, 1700, 1590 cm-1.

NMR (DMSO-d6) : of 1.37 (3H, t, J = 7,1 Hz), 4,4 (2H, K, J = 7,1 Hz), 7,82 (1H, DD, J = 7.9 Hz, 7.9 Hz), 8,1 - 8,18 (1H, m), 8,44 (1H, DD, J = 1,8 Hz, 1.8 Hz), 10,24 (1H, s).

MASS (m/z: 219 (M++ 1).

Elemental analysis for C10H10N4O2< / BR>
Calculated: C 55,04, H 4,62, N 25,68

Found: C 55,19, H br4.61, N 25,66

Preparative example 10.

A mixture of ethyl ester of 3-aminobutanol acid (2 g), hexane-2,5-dione (1.8 ml) and acetic acid(0.7 ml) in benzene (10 ml), boiled for 5 hours with simultaneous removal of water in the nozzle Dean-stark. To the mixture are added ethyl acetate and water added potassium carbonate in a mixture of set pH 8. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporation in vacuo get Adilov the CLASS="ptx2">

NMR (DMSO-d6) : of 1.33 (3H, t, J = 7,1 Hz), a 1.96 (6H, s), 4,32 (2H, K, J= 7,1 Hz), of 5.84 (2H, s), 7,55 - to 7.77 (3H, m), 8-8,8 (1H, m).

Preparative example 11.

A mixture of 3-hydrazinobenzene acid (2 g), 1,1,3,3-tetramethoxypropane (2.2 ml) and conc. hydrochloric acid (2.4 ml) in methanol (10 ml) is boiled for 2 hours and then evaporated in vacuum. The residue is dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine. Obtained by evaporation of the solvent the residue is purified column chromatography on silica gel with elution with dichloromethane. Containing the target product fractions are collected and their evaporation in vacuo get methyl ester 3-(pyrazole-1-yl)benzoic acid (1,33 g).

So pl. 48-50oC.

IR (nujol): 3130, 1705, 1610, 1590 cm-1.

NMR (DMSO-d6) : to 3.92 (3H, s), 6,57 - 6,63 (1H, m), 7,66 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,82 (1H, d, J = 1.6 Hz), 7,86 - 7,94 (1H, m), of 8.1 to 8.2 (1H, m), 8,4 - of 8.47 (1H, m) 8,64 (1H, d, J = 2.5 Hz).

MASS: 203 (M++1)

Elemental analysis for C11H10N2O2< / BR>
Calculated: C 65,34, H to 4.98, N 13,85

Found: C 65,11, H 4,94, N 13,78

Preparative example 12.

A mixture of methyl ester of 5-acetyl-3-pyridineboronic acid (3 g) and dimethylacetal N,N-dimethylformamide (6,7 ml) in tetrahydrofuran magnesium sulfate. The solvent is removed by concentration and rinsing residue diisopropyl ether get methyl ester 5-(3-dimethylamino-1-oxo-2-propenyl)-3-pyridineboronic acid (1.88 g).

So pl. 135 - 137oC.

IR (nujol): 1720, 1640, 1600 cm-1.

NMR (DMSO-d6) : 2,98 (3H, s), 3,19 (3H, s) to 3.92 (3H, s) 5,94 (1H, d, J = 12.1 Hz), to 7.84 (1H, d, J = 12.1 Hz), 8,63 (1H, DD, J = 2.1 Hz and 2.1 Hz) to 9.15 (1H, d, J = 2.1 Hz), to 9.32 (1H, d, J= 2.1 Hz).

Preparative example 13.

A mixture of methyl ester 5-(3-dimethylamino-1-oxo-2-propenyl)-3-pyridineboronic acid (1.7 g), acetic acid (0,62 ml) and hydrazine monohydrate (0.53 ml) in methanol (34 ml) is stirred 24 hours at room temperature and then evaporated in vacuum. To the residue add a mixture of tetrahydrofuran, ethyl acetate and water and adding potassium carbonate in a mixture of set pH 9. The separated organic layer was washed with brine and dried over magnesium sulfate. The solvent is removed by concentration and rinsing residue diisopropyl ether get methyl ester 5-(pyrazole-3-yl)-3-pyridineboronic acid (1.24 g).

So pl. 138-141oC.

IR (nujol): 3100, 1720, 1600 cm-1.

NMR (DMSO-d6) : 3,93 (3H, s), 6,98 (1H, s), 7,89 (1H, s) 8,64 (1H, s), 9,01 (1H, s), 9,27 (1 is ibullet thionyl chloride. After stirring the mixture for 30 minutes at the same temperature, add 5-(3-methyl-1,2,4-oxadiazol-5-yl)-3-pyridylcarbonyl acid (2.5 g) and the mixture is boiled for 3 hours. After cooling the mixture to room temperature, it is transferred into a mixture of ethyl acetate (100 ml) with water (100 ml). The organic layer is successively washed with 10% aqueous potassium carbonate solution and brine, then dried over magnesium sulfate. The solvent is evaporated in vacuo and recrystallization of the residue from diethyl ether to obtain methyl ester 5-(3-methyl-1,2,4-oxadiazol-5-yl)-3-pyridineboronic acid (2,12 g).

So pl. 131-132oC.

IR (nujol): 1720, 1610, 1100, 740 cm-1.

NMR (DMSO-d6) : 2,47 (3H, s), of 3.96 (3H, s), 8,77 (1H, DD, J = 2.1 Hz and 2.1 Hz), 9,31 (1H, d, J = 2.1 Hz), to 9.45 (1H, d, J = 2.1 Hz).

MASS: (m/z): 218 (M+-1).

Preparative example 15.

To a suspension of 1-(hydroxyimino)ethylamine (7,4 g) in dry tetrahydrofuran (450 ml) was carefully added sodium hydride (3.7 g, 60% in mineral oil). The mixture is stirred for 15 minutes at room temperature and boil for 30 minutes. To the obtained mixture is added 3,5-bis(methoxycarbonyl)pyridine (15 g) and the mixture is boiled for 3 hours. After cooling to room temperature the reaction mixture is transferred into sleepout pH 3.5. The formed precipitate is filtered off, washed with water and after drying in a vacuum get 5-(3-methyl-1,2,4-oxadiazol-5-yl)-3-pyridylcarbonyl acid (5,04 g).

So pl. 242-244oC (decomp.).

IR (nujol): 1710, 1455, 1170 cm-1.

NMR (DMSO-d6) : 2,47 (3H, s), 8,63 (1H, t, J = 2.1 Hz), 9.28 are (1H, t, J = 2.1 Hz), 9,41 (1H, d, J = 2.1 Hz),

MASS (m/z): 203 (M+- 2).

Preparative example 16.

A mixture of methyl ester 5-tert-butoxycarbonylamino-3-pyridineboronic acid (5.7 g) and conc. hydrochloric acid (11,4 ml) in methanol (57 ml) is stirred for 1 hour at 40oC. After cooling to room temperature the reaction mixture is transferred into a mixture of ethyl acetate (100 ml) with water (100 ml) under stirring and the addition of 10% aqueous potassium carbonate solution set pH 9. The organic layer was washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuo and recrystallization of the residue from a mixture of diethyl ether-methanol to obtain methyl ester of 5-amino-3-pyridineboronic acid (2,03 g).

So pl. 128-130oC.

IR (nujol): 3300, 3125, 1720, 1245, 1120 cm-1.

NMR (DMSO-d6) : of 3.84 (3H, s), between 7.4 to 7.5 (1H, m), 8,12 - of 8.15 (1H, m), and 8.2 and 8.3 (1H, m).

MASS: 151 (M+- 1).

Premigratory (2.2 g) in acetic acid (5 ml) is boiled for 30 minutes. After cooling to room temperature the reaction mixture was transferred into a stirred mixture of ethyl acetate (50 ml) with water (50 ml) and addition of 10% aqueous potassium carbonate solution set pH 8.5. The organic layer was washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuo and recrystallization of the residue from a mixture of diethyl ether-n-hexane get methyl ester 5-(pyrrol-1-yl)-3-pyridineboronic acid (1.29 g). So pl. 101-102oC.

IR: 1710, 1590, 1260 cm-1.

NMR (J-d6) : 3,93 (3H, s), 6,3 - 6,4 (2H, m), 7,55 - the 7.65 (2H, m), 8,35 an 8.4 (1H, m), 8,93 (1H, d, J = 1.7 Hz), 9,17 (1H, d, J = 2.7 Hz).

MASS: 203 (M+).

Elemental analysis for C11H10N2O3< / BR>
Calculated: C 65,34, H to 4.98, N 13,85

Found: C 65,11, H 5,03, N 13,63

Preparative example 18.

To stir at 0oC to a solution of 1-methylthio-2-bromine benzol (5 g) in dry ether (30 ml) for 15 minutes and added dropwise 1,63 M solution of utility in hexane (16.6 ml). The reaction mixture was stirred 1.5 hours at 0oC and then for 40 minutes, add to cooled to -78oC solution triisopropylsilane (7,4 ml) in tetrahydrofuran (40 ml). After stirring for 1 hour at -78oC, the reaction mixture olanow acid (40 ml) and the layers separated. The aqueous phase is extracted with ether (2 and 80 ml), the combined organic phases are washed with brine, dried over magnesium sulfate, evaporated and washed with petroleum ether (2x20 ml), get 2 methylthiophenethylamine.

So pl. 83-84oC.

IR (nujol): 3250, 1580, 1010, 740 cm01.

NMR (DMSO-d6) : to 2.41 (3H, s), 7,07 and 7.36 (4H, m), of 8.09 (2H, s).

MASS (m/z): 168 (M+).

Preparative example 19.

By the method similar to the method of preparative example 18, we obtain the following connections:

(1) 2-Methoxyphenylhydrazine

So pl. 105-106oC.

IR (nujol): 3350, 1600, 1220, 1160, 1050, 1020, 750 cm-1.

NMR (DMSO-d6) : of 3.8 (3H, s), 6,9 - 6,99 (2H, m), 7,39 (1H, DDD, J = 7.2 Hz, 7.2 Hz, 1.8 Hz), EUR 7.57 (1H, DD, J = 7,2 Hz, 1.8 Hz), and 7.7 (2H, s).

MASS (m/z): 152.

(2) 2-Triftormetilfullerenov

So pl. 144 - 145oC.

IR (nujol): 3250, 1100, 770, 720 cm-1< / BR>
NMR (DMSO-d6) : 7,5-to 7.67 (4H, m), with 8.33 (2H, s).

Preparative example 20.

A mixture of 2-methylthiophenethylamine (1.55 g) and 3-iodine-benzoic acid (2,08 g) in water (30 ml) was stirred at room temperature, then add sodium carbonate (2.67 g) and palladium acetate (11) is 0.019 g). After the lane is 6 N. hydrochloric acid in the aqueous layer set pH 2. The crystalline product is separated, washed out and after drying, the obtained 3-(2-methylthiophenyl)benzoic acid.

IR (nujol): 1680, 1275, 945, 759 cm-1.

Preparative example 21.

By the method similar to the method of preparative example 20, the following connections:

(1) 3-(2-Were)benzoic acid

So pl. 135-137oC.

IR (nujol): 1670, 750 cm-1.

NMR (DMSO-d6) : of 2.23 (3H, s), a 7.2 to 7.35 (4H, m), EUR 7.57 - to 7.64 (2H, m), 7,86 (1H, s), 7,93 - 7,98 (1H, m), of 13.05 (1H, sh.S.).

MASS (m/z): 211 (M+-1).

(2) 3-(4-Methoxyphenyl)benzoic acid

So pl. 212-213oC.

IR (nujol): 1675, 1250, 1020 cm-1.

NMR (DMSO-d6) : 3,81 (3H, s), 7,05 (2H. DD, J = 6,7 Hz and 2.1 Hz), 7,56 (1H, DD, J = 7,7 Hz, 7.7 Hz), the 7.65 (2H, DD, J = 6,7 Hz and 2.1 Hz), a 7.85 to $ 7.91 (2H, m) to 8.14 (1H, DD, J = 1.7 Hz, 1.7 Hz), 13,07 (1H, sh.S.).

MASS (m/z: 227 (M+-1).

(3) 3-(3-Methoxyphenyl)benzoic acid

So pl. 129-131oC.

IR (nujol): 1690, 1310, 1210, 1040, 750 cm-1.

NMR (DMSO-d6) : of 3.84 (3H, s), of 6.96 - 7,01 (1H, m), 7,21 - 7,28 (2H, m), 7,42 (1H, DD, J = 7.9 Hz, 7.9 Hz), to 7.59 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,9 - of 7.97 (2H, m), 8,18 (1H. DD, J = 1.5 Hz, 1.5 Hz).

MASS (m/z): (M+-1).

(4) 3-(1-NAF is CO-d6) : 7,47 - 7,79 (7H, m), 7,98 - of 8.09 (4H, m)

MASS (m/z: 247 (M+-1).

(5) 3-(2-Naphthyl)benzoic acid

So pl. 213-215oC.

IR (nujol): 1670, 1310, 1250, 810, 750 cm-1.

NMR (DMSO-d6) : 7,52 - 7,71 (3H, m), 7,86 - 8,11 (6H. m), and 8.3 (1H, s) of 8.37 - 8,39 (1H, m), 13,17 (1H, sh.S.).

MASS (m/z: 247 (M+-1).

(6) 3-(2-Methoxyphenyl)benzoic acid

So pl. 176-178oC.

IR (nujol): 1690, 1310, 1250, 1020, 720 cm-1.

NMR (DMSO-d6) : of 3.78 (3H, s), 7.03 is - 7,16 (2H, m), 7.3 to 7,42 (2H, m), 7,54 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,72 (1H, DDD, J = 7.9 Hz, 1.6 Hz, 1.6 Hz), to $ 7.91 (1H, DDD, J = 7.7 Hz, 1.5 Hz, 1.5 Hz), with 8.05 (1H, DD, J = 1.6 Hz, 1.6 Hz), 13,02 (1H, sh.C).

MASS (m/z: 227 (M+-1).

(7) 3-(2-Triptoreline)benzoic acid

IR (nujol): 1680, 1310, 1110, 750 cm-1.

Preparative example 22.

By the method similar to the method of preparative example 2, the following compounds:

(1) Methyl ester 3-(4-methoxyphenyl)benzoic acid

So pl. 62-64oC.

IR (nujol): 1720, 1610, 1020, 835 cm-1.

NMR (DMSO-d6) : 3,81 (3H, s) to 3.89 (3H, s), 7,05 (2H, DD, J = 7.9 Hz, 1.7 Hz), to 7.59 (1H, DD, J = 7.9 Hz, 7.9 Hz), the 7.85 - of 7.95 (2H, m), 8,15 (1H, DD, J = 1.7 Hz).

MASS (m/z: 243 (M + 1)

(2) Methyl ether 3-(3-methoxyphenyl)benzoic acid,02 (1H, m), 7,21 - 7,28 (2H, m), 7,42 (1H, DD, J = 7,7 Hz, 7.7 Hz), a 7.62 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,94 - to 7.99 (2H, m), 8,18 (1H, DD, J = 1.7 Hz, 1.7 Hz).

MASS (m/z: 243 (M++ 1)

(3) Methyl ether (1-naphthyl)benzoic acid

So pl. 73-74oC.

IR (nujol): 1720, 1300, 1260, 1240, 1100, 800, 770, 750 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 7,47 for 7.78 (7H, m), 7,99 of 8.1 (4H, m)

MASS (m/z): 263 (M++ 1)

(4) Methyl ester 3-(2-naphthyl)benzoic acid

So pl. 51-52oC.

IR (nujol): 1720, 1290, 1250, 1110, 810, 750 cm-1.

NMR (DMSO-d6) : 3,93 (3H, s), 7,52 - 7,72 (3H, m), 7,85 -8,13 (6H, m), 8,29 (1H, s), at 8.36 (1H. C).

MASS (m/z): 263 (M++ 1).

(5) Methyl ester 3-(2-methoxyphenyl)benzoic acid

So pl. 91-93oC.

IR (nujol): 1710, 1310, 1250, 1100, 1020, 760 cm-1.

NMR (DMSO-d6) : of 3.78 (3H, s), 3,88 (3H, s), 7,05 - 7,16 (2H, m), 7.3 to 7.4 (2H, m), EUR 7.57 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,76 (1H, DDD, J = 8 Hz, 1.6 Hz, 1.6 Hz), to 7.93 (1H, DDD, J = 7.8 Hz, 1.5 Hz, 1.5 Hz), 8,07 (1H, DD, J = 1.6 Hz, 1.6 Hz).

MASS (m/z: 243 (M++1).

(6) Methyl ester 3-(2-triptoreline)benzoic acid

So pl. 41-43oC.

IR (nujol): 1730, 1310, 1240, 1170, 1130, 1040, 740 cm-1.

NMR (DMSO-d6) : a 3.87 (3H, s), 7,46 (1H, d, J = 7,3 Hz), 7,62 - 7,8 (4H, m), a 7.85 - 7,88 (2H, m), 7,99 - of 8.06 (1H, m).

the 00, 1240, 1110, 970, 740 cm-1.

NMR (DMSO-d6) : 2,22 (3H, s), 3,88 (3H, s), 7,21 - to 7.35 (4H, m), 7,6 - to 7.67 (2H, m), 7,88 (1H, DD, J = 1.5 Hz, 1.5 Hz), of 7.97 (1H, DDD, J = 6,9 Hz, 1.9 Hz, 1.9 Hz).

MASS (m/z: 227 (M++1).

(8) Methyl ester 3-(2-methylthiophenyl)benzoic acid

So pl. 91-92oC.

IR (nujol): 1710, 1300, 1230, 750 cm-1.

NMR (DMSO-d6) : of 2.38 (3H, s), a 3.87 (3H, s), 7,22 - of 7.3 (2H, m), 7,35 - 7,46 (2H, m), 7,56 - to 7.68 (2H, m), 7,94 shed 8.01 (2H, m)

MASS (m/z): 259 (M++1).

Preparative example 23.

By the method similar to the method of preparative example 5, the following compounds:

(1) Methyl ester of 4-n-butyl-3-(pyrrol-1-yl)benzoic acid.

IR (film): 1720, 1610 cm-1.

NMR (DMSO-d6) : of 0.77 (3H, t, J = 7,1 Hz), of 1.05 to 1.45 (4H, m), 2,48 of 2.6 (2H, m), 3,85 (3H, s), 6.22 per 6,28 (2H, m), 6,91 - of 6.96 (2H, m), 7,55 (1H, d, J = 8 Hz), 7,72 (1H, d, J = 1.7 Hz), to 7.93 (1H, DD, J = 1.7 Hz, 8 Hz).

(2) Methyl ether 4-methyl-3-(pyrrol-1-yl)benzoic acid

So pl. 46oC.

IR (nujol): 1715 cm-1.

NMR (DMSO-d6) : of 2.25 (3H, c), 3,86 (3H, c), 6,23 - of 6.29 (2H, m), 6,95 - 7,01 (2H, m), 7,53 (1H, d, J = 7.9 Hz), 7,74 (1H, d, J = 1,8 Hz), 7,88 (1H, DD, J = 7.9 Hz).

(3) Methyl ester 5-cyano-3-(pyrrol-1-yl)benzoic acid

So pl. 124-126oC.

IR (nugo,32 (1H, DD, J = 1.4 Hz, 2.3 Hz), to 8.45 (1H, DD, J = 1.4 Hz, 2.3 Hz).

(4) Methyl ether 3-chloro-5-(pyrrol-1-yl)benzoic acid

So pl. 70-72oC.

IR (nujol): 1720, 1580, 1340, 1260, 760, 720 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, c), 6,3 to 6.35 (2H, m), 7.5 to at 7.55 (2H, m), 7,75 one - 7.8 (1H, m), 8 - 8,03 (1H, m), 8,03 - of 8.06 (1H, m).

MACC (m/z): 236 (M + 1).

(5) Methyl ester 3-(3-formylphenol-1-yl)benzoic acid

IR (film): 1720, 1665, 1590 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 6,72 (1H, DD, J = 1.6 Hz, 3.1 Hz), to 7.61 - the 7.65 (1H, m), to 7.67 - 7,74 (1H, 1H, m), to $ 7.91 - of 8.04 (2H, m), 8,12 - 8,18 (1H, m), 8,35 an 8.4 (1H, m), (1H, m), 9,81 (1H, s).

(6) Methyl ester of 4-hydroxy-3-(pyrrol-1-yl)benzoic acid

So pl. 98-100oC.

IR (nujol): 3220, 1677, 1605 cm-1.

NMR (DMSO-d6) : is 3.82 (3H, c), 6,17 - 6,23 (2H, m), 7,07 - 7,19 (3H, m), 7,74 - a 7.85 (2H, m), 11 (1H, s)

Preparative example 24.

A mixture of dimethyl 5-(pyrrol-1-yl)isophthalic acid (3 g), methyl acetate (0,86 g) and sodium methoxide (0,81 g) in N,N-dimethylformamide (21 ml) is heated 3 hours at 55oC. After cooling to room temperature the reaction mixture is transferred into water (100 ml) and addition of 10% hydrochloric acid to establish a pH of 3. The formed precipitate was separated and washed with water. The resulting crude product was then purified the content of the target product fractions are collected and evaporated in vacuum. Precrystallization of the residue from methanol to obtain methyl ester of 3-[3-methoxycarbonyl-5-(pyrrol-1-yl)phenyl]-3-oxopropanoic acid (0.31 g).

So pl. 82-84oC.

IR (nujol): 1720, 1690, 1260, 720 cm-1.

NMR (DMSO-d6) : 3,68 (3H, s), 3,93 (3H, s), 4,42 (2H, s), 6,3 - 6,4 (2H, m), 7,55 - the 7.65 (2H, m), 8,29 (2H, s), a 8.34 (1H, s).

MACC (m/z): 300 (M - 1).

Preparative example 25.

A solution of methyl ester 3-/3-methoxycarbonyl-5-(pyrrol-1-yl) phenyl/-3-oxopropanoic acid (0.1 g) in a mixture of water (1 ml), methanol (3 ml) and concentrated sulfuric acid (40 mg) is boiled for 16 hours. After cooling to room temperature the reaction mixture is transferred into a mixture of ethyl acetate (50 ml) with water (50 ml). The organic layer is successively washed with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate and after evaporation in vacuo receive the methyl ester of 3-acetyl-5-(pyrrol-1-yl)benzoic acid (20,1 mg).

So pl. 101-103oC.

IR (nujol): 1720, 1690, 1230, 730 cm-1.

NMR (DMSO-d6) : a 2.71 (3H, s), 3,93 (3H, s), 6,3 - 6,36 (2H, m), of 7.36 - to 7.59 (2H, m), 8,25 - 8,33 (3H, m).

MACC (m/z: 243 (M+).

Preparative example 26.

A suspension of 1-three(n-butyl)stannyl-2-(4,4-dimethyl-4,5-adiya (0,29 g) in dioxane is boiled for 18 hours. After cooling to room temperature, to the reaction mixture is added 25% aqueous solution of potassium fluoride (11 ml) and the mixture is stirred for 15 minutes. The insoluble matter is filtered off with celite. The filtrate is extracted with ethyl acetate (50 ml), washed with brine, dried over filter magnesium, filtered and evaporated in vacuum. The residue is purified column chromatography on silica gel (200 g) with a mixture of benzene-ethyl acetate (20:1) as eluent. Containing the target compound fractions are combined and evaporated methyl ester 3-[2-(4,4-dimethyl-4,5-dihydrooxazolo-2-yl)phenyl]benzoic acid (370 mg).

So pl. 103-104oC.

IR (nujol): 1710, 1635, 1300, 745 cm-1.

NMR (DMSO-d6) : of 1.17 (6H, s), with 3.79 (2H, s), 3,86 (3H, s), and 7.3 to 7.7 (7H, m), 7,9 - 8 (2H, m).

MACC (m/z): 310 (M + 1).

Preparative example 27.

By the method similar to the method of preparative example 26, the following connections:

(1) Methyl ester 3-(thiophene-3-yl)benzoic acid

So pl. 50-51oC.

IR (nujol): 1710, 1285, 1235, 780, 745 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 7,54 - 7,71 (3H, m), a 7.85 - 7,9 (1H, m), 7,98 - with 8.05 (2H, m), 8,23 - of 8.25 (2H, m),.

MACC (m/z: 219 (M + 1).

(2) Methyl ether 3-(thiophene-2-yl)benzoic acid the 5 - 8 (2H, m), 8,16 - 8,17 (1H, m).

MACC (m/z: 219 (M + 1).

(3) Methyl ester 3-(thiazol-2-yl)benzoic acid

So pl. 50-52oC.

IR (nujol): 1700, 1295, 1220, 755 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), to 7.68 (1H, d, J = 7.8 Hz), 7,88 (1H, d, J = 3.2 Hz), to 7.99 (1H, d, J = 3.2 Hz), 8,03 - of 8.09 (1H, m), 8,19 - of 8.25 (1H, m), 8,49 - 8,51 (1H, m).

MACC (m/z): 220 (M + 1).

(4) Methyl ester 3-[4-(4,4-dimethyl-4,5-dihydrooxazolo-2-yl) phenyl] benzoic acid

IR (net): 2950, 1720, 1640, 1440, 1300, 1240 cm-1.

NMR (DMSO-d6) : of 1.31 (6H, s) of 3.9 (3H, s), 4,14 (2H, s), 7,66 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,82 (2H, d, J = 8.5 Hz), 7,94 - with 8.05 (4H, m), 8,24 (1H, s).

MACC (m/z): 310 (M++ 1).

Preparative example 28.

To a solution of methyl ester of 3-[2-(4,4-dimethyl-4,5-dihydrooxazolo-2-yl)phenyl] benzoic acid (1.25 g) in pyridine (5 ml) and 7oC added dropwise phosphorylchloride (0.75 ml), keeping the temperature below 20oC. Then the reaction mixture is stirred for 4 hours at 100oC. After cooling to room temperature, the mixture is neutralized with water and the emulsion is extracted with ethyl acetate (50 ml). The organic layer is successively washed with 6 N. hydrochloric acid and brine, dried over magnesium sulfate, filtered and evaporated in vacuum. The residue is purified of colonos the tion are combined and evaporated in vacuum. By recrystallization of the crystalline residue from methanol to obtain methyl ester of 3-(2-cyanophenyl)benzoic acid (0.7 g).

So pl. 83-85oC.

IR (nujol): 2225, 1720, 1245, 730 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s), 7,5 - 8,2 (8H, m).

MACC (m/z): 238 (M + 1).

Preparative example 29.

By the method similar to the method of preparative example 28, the following connection:

Methyl ester of 3-(4-cyanophenyl)benzoic acid

So pl. 123-125oC.

IR (nujol): 2230, 1720 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s), to 7.68 (1H, d, J = 7.8 Hz, 8 Hz), 7,9 - 8,06 (6H, m), of 8.25 (1H, s).

MACC (m/z): 238 (M + 1).

Preparative example 30.

To a mixture of 3-methoxycarbonyl-5-(pyrrol-1-yl)benzoic acid (3 g), 4-hydroxypiperidine (1,23 g) and 1-hydroxybenzotriazole (1,81 g), in dichloromethane (100 ml) under cooling was added 1-ethyl-3-(3-dimethylamino)carbodiimide (to 2.57 g) and the solution stirred for 30 hours at room temperature. After evaporation of the solvent the residue is dissolved under stirring in a mixture of ethyl acetate with saturated aqueous sodium bicarbonate. The organic layer is successively washed with water and brine and dried over magnesium sulfate. Rastvoriteli-methanol (50: 1). The content of the target product fractions are collected and after evaporation in vacuo receive the methyl ester of 3-[(4-hydroxypiperidine-1-yl)carbonyl]-5-(pyrrol-1-yl)benzoic acid (of 3.56 g).

So pl. 158-159oC.

IR (nujol): 3350, 1730, 1600 cm-1.

NMR (DMSO-d6) : 1,2-2 (4H, m), 3 to 4.2 (6H, m), 3,91 (3H, s), 6,3 - 6,4 (2H, m), and 7.5 and 7.6 (2H, m), 7,7 - 7,8 (1H, m), 7,9 - 8 (1H, m), of 8.1 to 8.2 (1H, m)

MASS: (m/z): 329 (M++ 1).

Preparative example 31.

By the method similar to the method of preparative example 30, the following connections:

(1) Methyl ester 3-[(2-dimethylaminoethyl)carbarnoyl] -5-(pyrrol-1-yl)benzoic acid

So pl. 108-109oC.

IR (nujol): 3370, 1720, 1640, 1600 cm-1.

NMR (DMSO-d6) : of 2.28 (6H, s), 2,5 - 2,6 (2H, m), 3,5 - 3,6 (2H, m), 3,98 (3H, s), 6,3 - 6,4 (2H, m), 6,97 (1H, sh.(C) and 7.1 to 7.2 (2H, m), 8,1 - 8,3 (3H, m).

MASS (m/z): 316 (M++ 1).

(2) Methyl ether 3-[(4-methylpiperazin-1-yl)carbonyl] -5-(pyrrol-1-yl)benzoic acid

IR (film): 2950, 2800, 1720, 1630, 1600 cm-1.

NMR (DMSO-d6) : 2,2 (3H, s), 2,1 - 2,5 (6H, m), 3.5 to 3.8 (2H, m), 3,91 (3H, s), 6,3 - 6,4 (2H, m), and 7.5 and 7.6 (2H, m), 7,7 - 7,8 (1H, m), 7,9 - 8 (1H, m), of 8.1 to 8.2 (1H, m).

MASS (m/z): 328 (M++ 1).

Preparative example 32.

To a mixture of hydrochloride is a new ester 3-(3-formylphenol-1-yl)benzoic acid (10.2 g) and all is stirred for 3 hours at room temperature. Then by concentration to remove the solvent. To the residue is added a mixture of ethyl acetate, tetrahydrofuran and water and add 6 N. hydrochloric acid in a mixture of set pH 2. The separated organic layer was washed with brine, dried over magnesium sulfate and after evaporation in vacuo receive in the form of oil methyl ester 3-[(3-(gidroksilaminami)pyrrol-1-yl] benzoic acid (9,24 g).

IR (film): 3170 (W.) 1720 (sh.) cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s), 6.5 to 6,54 and 6.68 - 6,72 (total 1H, each m), 7,31 - to 7.77 (3H, m), 7,81 - of 7.95 (2H, m), 7,98 - of 8.06 (2H, m), and at 10.64 11,17 (total 1H, each s).

Preparative example 33.

By the method similar to the method of preparative example 32, the following connection:

Methyl ester 3-(2-gidroksilaminami)-pyrrol-1-yl)benzoic acid

IR (film): 3150, 1720 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 6,29 - 6,34 and 6,34 - 6,4 (total 1H, each m), 6,61 - 6,66 and 7,28 - 7,32 (total 1H, each m), 7.03, and a 7.85 (total 1H, each s), 7,12 - 7,17 and 7,16 - 7,2 (total 1H and each m), of 7.64 to 7.75 (2H, m), 7,82 - 7,88 (1H, m), of 7.96 - to 8.12 (1H, m), 10,88 t 11,49 (total 1H, each with).

Preparative example 34.

To a mixture of hydroxylamine hydrochloride (1.5 g) and 20% methanol solution of sodium methoxide (4.9 g) in methanol (50 ml) add the re. The solvent is removed by concentration and the residue dissolved in a mixture of ethyl acetate with water. The addition of 6 N. hydrochloric acid in a mixture of set pH 2. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuum. The residue is subjected to column chromatography on silica gel with elution with a mixture of chloroform-ethyl acetate (19: 1). Eluruume first fraction containing the target product, collected, evaporated in vacuum and after rinsing with a mixture of diisopropyl ether and n-hexane receive the methyl ester of 3-[(E)-2-gidroksiiminobetulonovoi-1-yl] benzoic acid (compound A) (0.8 g). Eluruume later fractions containing the target product, collected and after evaporation in vacuo receive the methyl ester of 3-[(Z)-2-gidroksiiminobetulonovoi-1-yl] benzoic acid (compound B) (1,43 g) in the form of butter.

Compound 4:

So pl. 87-88oC.

IR (nujol): 1720, 1590 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 6,29 - 6,34 (1H, m), 6,61 of 6.66 (1H, m), 7,12 - 7,17 (1H, m), of 7.64 - 7,72 (2H, m), 7,82 - 7,88 (1H, m), a 7.85 (1H, s), of 7.96 - 8,08 (1H, m), 10,85 (1H, s).

MASS (m/z): 245 (M++ 1).

Compound B:

IR (film): 1705-1725, 1630, 1590 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 6,34 is 6.4 (1H, m, 7,03 (1H, s), 7,16 to 7.2 (1H, is artigny example 35.

A mixture of methyl ester 3-(3-gidroksiiminobetulonovoi-1-yl)benzoic acid (9 g) and acetic anhydride (45 ml) is boiled with stirring for 3 hours and then the reaction mixture was concentrated in vacuo. To the residue is added a mixture of ethyl acetate with water and adding potassium carbonate establish a pH of 8. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuum. The residue is purified column chromatography on silica gel with elution by chloroform. Eluruume the fractions containing the desired product are pooled and evaporated in vacuum. Rinse residue with a mixture of diisopropyl ether and n-hexane get methyl ester 3-(3-cyanoprop-1-yl)benzoic acid (6.2 g).

So pl. 105-106oC.

IR (nujol): 2230, 1725, 1590 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s) of 6.73 - 6,79 (1H, m), 7,62 - 7,74 (2H, m), to $ 7.91 - to 7.99 (2H, m), 8,1 - of 8.15 (1H, m), 8,32 - of 8.37 (1H, m).

MASS (m/z: 227 (M++ 1).

Preparative example 36.

By the method similar to the method of preparative example 35, the following connection:

Methyl ester 3-(2-cyanoprop-1-yl)benzoic acid

So pl. 89 - 90oC.

IR (nujol): 2220, 1715, 1590 cm-1.

NMR (DMSO-d6) : 3,91 (3H (2H, m).

Preparative example 37.

To a solution of methyl ester 3-acetoxymethyl-5-(pyrrol-1-yl)benzoic acid (4.68 g) in dichloromethane (94 ml) is added at -20oC in nitrogen atmosphere chlorosulfonylisocyanate (2.1 ml). After stirring 1 hour at -20oC to the reaction mixture at the same temperature, add N,N-dimethylformamide (14 ml). After stirring 1 hour in the temperature range from -20oC to -10oC the reaction mixture is transferred into water and the product extracted with ethyl acetate. The extract was washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuo and the residue purified column chromatography on silica gel with elution by the mixture hexane-ethyl acetate (5:1). Eluruume fraction containing the target product, collect and evaporation in vacuo get methyl ether 3-acetoxymethyl-5-(2-cyanoprop-1-yl)benzoic acid (4.26 deaths / g).

So pl. 85-84oC.

IR (nujol): 2220, 1735, 1720 cm-1.

NMR (DMSO-d6) : 2,11 (3H, s), 3,91 (3H, s), of 5.24 (2H, s), 6,4 - 6,6 (1H, m), 7,2 - 7,3 (1H, m), and 7.6 to 7.7 (1H, m), of 7.9 to 8.1 (3H, m).

MASS (m/z): 299 (M++ 1).

Preparative example 38.

To a mixture of methyl ester 3-(2-dimethylaminomethylene-1-yl)benzoic acid (1 g) and d is stirred for 5 minutes at the same temperature. To a cooled ice mixture are added dropwise chlorosulfonylisocyanate (0.4 ml) and the mixture is stirred for 1 hour at the same temperature. To a cooled ice mixture are added dropwise N,N-dimethylformamide (3 ml) and the mixture is stirred for 1 hour at the same temperature. Then the reaction mixture is transferred into a mixture of dichloromethane with water and add 5 n sodium hydroxide solution in the separated aqueous layer set pH 12. Then the aqueous layer was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and after evaporation in vacuo get methyl ester 3-(2-cyano-5-dimethylaminomethylene-1-yl)benzoic acid (1.1 g) in the form of butter.

IR (nujol): 3450, 2220, 1728 cm-1.

NMR (DMSO-d6) : 2,04 (6H, s), 3,21 (2H, s) of 3.9 (3H, s), 6,37 (1H, d, J = 3,9 Hz), 7,17 (1H, d, J = 3,9 Hz), 7,74 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,78 - 7,86 (1H, m), 8,06 - 8,16 (2H, m).

Preparative example 39.

A solution of methyl ester 3-(2-methylthiophenyl)benzoic acid (1.4 g) in chloroform (21 ml) is stirred in a bath with ice in a nitrogen atmosphere. To the solution is slowly added m-chlorbenzoyl acid and the mixture is stirred for 5 hours at room temperature. Then the reaction mixture was extracted with chloroform (70 ml). The extract is successively washed with water the om and dried over magnesium sulfate. After evaporation of the solvent by recrystallization of the residue from diethyl ether to obtain methyl ester of 3-(2-methylsulfinylphenyl)benzoic acid.

So pl. 100-102oC.

IR (nujol): 1710, 1300, 1150, 950, 750 cm-1.

NMR (DMSO-d6) : 2,87 (3H, s), a 3.87 (3H, s), 7,44 (1H, DD, J = 7,4 Hz, 1.4 Hz), to 7.61 one - 7.8 (4H, m), of 7.96 (1H, DD, J = 1.5 Hz, 1.5 Hz), of 8.04 (1H, DDD, J = 7.5 Hz, 1.6 Hz, 1.6 Hz), to 8.12 (1H, DD, J = 7.5 Hz, 1.5 Hz).

Preparative example 40.

A mixture of methyl ester 3-(2-trichloroacetonitrile-1-yl)-benzoic acid (10 g), benzyl ether (3.3 ml) and potassium carbonate (4.4 g) in N,N-dimethylformamide (30 ml) is stirred for 6 hours at room temperature. Then the reaction mixture is transferred into water and the mixture extracted with ethyl acetate. The extract is washed with water, dried over magnesium sulfate and evaporated. The residue is purified column chromatography on silica gel with elution with toluene. Eluruume fraction containing the target product, collect and evaporation in vacuo receive in the form of oil methyl ester 3-(2-benzyloxycarbonylamino-1-yl)benzoic acid (8,35 g).

IR (film): 1700-1725 (sh.). 1590 cm-1< / BR>
NMR (DMSO-d6) : a 3.87 (3H, s), 5,12 (2H, s), 6,37 (1H, DD, 2.7 Hz, 3.9 Hz), 7,14 (1H, DD, J = 1,8 Hz, 3.9 Hz), 7,21 - to 7.35 (6H, m), EUR 7.57 - of 7.69 (2H, sh), 7,8 - to 7.84 (1H, m), the lots (20 g), dimethylamine hydrochloride (12.2 g) and paraformaldehyde (13,4 g) in ethanol (60 ml) is boiled with stirring for 3 hours. After removal of the solvent by concentration, the residue is transferred into a mixture of ethyl acetate with water. By adding 5 n sodium hydroxide solution in a mixture of set pH 12. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue is purified column chromatography on silica gel with elution with a mixture of chloroform-methanol (9: 1, vol/vol.). Eluruume fraction containing the target product, collect and evaporation in vacuo get methyl ester 3-(2-dimethylaminomethylene-1-yl)benzoic acid (15.3 g) in the form of butter.

IR (nujol): 1728, 1605, 1590 cm-1.

NMR (DMSO-d6) : to 2.13 (6H, s), and 3.2 (2H, s), 3,88 (3H, s), 6,15 - 6,23 (2H, m),? 7.04 baby mortality, and 7.1 (1H, m), a 7.62 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,8 - 7,88 (1H, m), 7,88 - of 7.96 (1H, m), 8,29 - to 8.34 (1H, m).

MASS (m/z): 259 (M++ 1).

Preparative example 42.

To a mixture of methyl ester 3-(2-dimethylaminomethylene-1-yl)benzoic acid (10 g) and ethyl acetate (50 ml) is added at room temperature mediaite (4.8 ml) and the mixture is stirred for 2 hours at the same temperature. The formed precipitate is filtered off and after drying receive methyl ester 3-(2-nujol): 3430, 1720, 1585 cm-1< / BR>
NMR (DMSO-d6) : was 2.76 (9H, s) to 3.89 (3H, s), 7,54 (2H, s, to 6.39 (1H, DD, J = 2,9 Hz, 3.5 Hz), 6,69 (1H, DD, J = 1.7 Hz, 3.5 Hz), 7.23 percent (1H, DD, J = 1.7 Hz, 2.9 Hz), 7,65 - 7,8 (2H, m), 7,89 - to 7.93 (1H, m), 8 and 8.1 (1H, m)

Preparative example 43.

To a mixture of methyl ester iodide 3-(2-trimethylaminoethyl-1-yl)benzoic acid (2 g) and 1,3-dimethylimidazolidin-2-she (6 ml) is added a complex of borane-pyridine (1.1 ml) and the mixture is stirred for 1.5 hours at 105oC. After adding to the mixture dichloromethane her successively washed with water, 1 N. hydrochloric acid and water. The mixture is dried over magnesium sulfate and after evaporation in vacuo receive in the form of oil methyl ester 3-(2-methylpyrrole-1-yl)benzoic acid (1.01 g).

IR (nujol): 1725, 1588 cm-1.

NMR (DMSO-d6) : to 2.18 (3H, s) to 3.89 (3H, s), 6 - 6,04 (1H, m), 6,09 - x 6.15 (1H, m), 6.89 in - 6,94 (1H, m), 7,55 to 8.1 (4H, m).

MASS (m/z): 216 (M++ 1).

Preparative example 44.

To a mixture of methyl ester 3-(2-trichloroacetonitrile-1-yl)benzoic acid (1 g) and N,N-dimethylformamide (2 ml) was added 28% aqueous ammonia solution (0.4 ml) and the mixture is stirred for 1.5 hours at room temperature. The mixture is then transferred into water-ethyl acetate. The separated organic layer is washed with water, dried over sulfate Magnetrol-1-yl)benzoic acid (0,61 g).

So pl. 157 - 158oC.

IR (nujol): 3400, 3200, 1715, 1650, 1610 cm-1.

NMR (DMSO-d6) : a 3.87 (3H, c), 6,22 - of 6.29 (1H, m), 6,9 - 6,98 (2H, m), 7,09 - 7,14 (1H, m), 7,53 and 7.6 (2H, m), 7,63 (1H, c), 7,76 (1H, c), 7,87 - of 7.96 (1H, m).

Preparative example 45.

To a mixture of methyl ester 3-(2-benzyloxycarbonylamino-1-yl)benzoic acid (0.5 g) and dioxane (20 ml) was added 1 n sodium hydroxide solution (1.5 ml) and the mixture is stirred for 3 days at room temperature. The mixture is then transferred into water-ethyl acetate and addition of 1 N. hydrochloric acid in the separated organic layer set pH 1. The mixture is extracted with ethyl acetate, the extract washed with water and dried over magnesium sulfate. The solvent is removed by concentration and rinsing the residue with n-hexane receive 3-(2-benzyloxycarbonyl)benzoic acid (0.24 g).

So pl. 161 to 165oC.

IR (nujol): 1710 cm-1.

NMR (DMSO-d6) : to 5.13 (2H, s), 6,36 (1H, DD, J = 2,8 Hz, 3.9 Hz), 7,13 (1H, DD, J = 1.7 Hz, 3.9 Hz), 7,21 - 7,37 (6H, m), 7.5 to 7,66 (2H, m), 7,78 - 7,83 (1H, m), 7,92 - 8 (1H, m), 13,1 (1H, m).

Preparative example 46.

By the method similar to the method of preparative example 45, the following connections:

(1) 3-(3-Cyanoprop-1-yl)benzoic acid

So pl. 194-196oC.<), 7,87 - 7,98 (2H, m), 8,08 - to 8.14 (1H, m), 8,31 - of 8.37 (1H, m)

(2) 3-(2-Cyanoprop-1-yl)benzoic acid

So pl. 195-196oC.

IR (nujol): 2220, 1690-1705 (W.), 1590 cm-1.

NMR (DMSO-d6) : 6,48 (1H, DD, J = 2,8 Hz, 3.9 Hz), 7,27 (1H, DD, J = 1.6 Hz, 3.9 Hz), to 7.64 (1H, DD, J = 1.6 Hz, 2.8 Hz), 7,73 (1H, DD, J = 8,1 Hz, 8.1 Hz), 7,81 - 7,89 (1H, m), 8,02 - of 8.09 (2H, m).

MASS (m/z): 221 (M+- 1).

(3) 5-Cyano-3-(pyrrol-1-yl)benzoic acid

So pl. 181-184oC.

IR (nujol): 2230, 1700, 1600 cm-1.

NMR (DMSO-d6) : of 6.31 - 6,37 (2H, m), 7,55 to 7.62 (2H, m), 8,11 (1H, DD, J = 1.4 Hz and 1.4 Hz), 8,31 (1H, DD, J = 1.4 Hz, 2.3 Hz), 8,42 (1H, DD, J = 1.4 Hz, 2.3 Hz).

Preparative example 47.

To a cooled ice mixture of methyl ester of 3-(pyrrol-1-yl)benzoic acid (2 g) and N,N-dimethylformamide (20 ml) is added N-chlorosuccinimide (2.7 g) and the mixture is stirred for 20 hours at room temperature. Then the reaction mixture is transferred into a mixture of ethyl acetate with water and adding potassium carbonate in a mixture of set pH 8. The separated organic layer was washed with water, dried over magnesium sulfate and after evaporation in vacuo get methyl ester 3-(2,5-dichloroprop-1-yl)benzoic acid (2,44 g) in the form of butter.

IR (film): 1725, 1590 cm-1.

NMR (DMSO-d6) :8.

To a cooled ice N,N-dimethylformamide (4.6 ml) was added dropwise phosphorylchloride (5.5 ml) and the mixture stirred for 15 minutes at 40-50oC. To this mixture at room temperature a solution of methyl ester of 3-(pyrrol-1-yl)benzoic acid (6 g) in N,N-dimethylformamide (30 ml) and everything is stirred for 3 hours at 110-120oC. Chilled with ice, the mixture is transferred into ice-cold water and adding potassium carbonate in a mixture of set pH 9. The mixture is then extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated in vacuum. Rinse residue diisopropyl ether get methyl ester 3-(2-formylphenol-1-yl)benzoic acid (5.31g).

So pl. 61-64oC.

IR (nujol): 1720, 1660, 1590 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), and 6.5 (1H, DD, J = 2,6 Hz, 3.9 Hz), 7,28 (1H, DD, J = 1.7 Hz, 3.9 Hz), 7.5 to at 7.55 (1H, m), the 7.65 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,69 - to 7.77 (1H, m), 7,88 - a 7.92 (1H, m), 7,97 - with 8.05 (1H, m), 9,54 (1H, s).

Preparative example 49.

A mixture of methyl ester of 4-hydroxy-3-(pyrrol-1-yl)benzoic acid (4 g), acetone (40 ml) and p-toluenesulfonic acid (0.8 g) in toluene is boiled with stirring for 15 hours. After removal of solvent evaporation the residue is added a mixture of ethyl acetate with water. Adding carborne and evaporated in vacuum. The residue is purified column chromatography on silica gel with elution with a mixture of toluene with n-hexane (1:1, vol/vol.). Eluruume fraction containing the target product are collected and evaporated in vacuum. Rinse residue with a mixture of diisopropyl ether and n-hexane receive 8-methoxycarbonyl-4,4-dimethyl-4H-pyrrolo/2,1-C//1.4/benzoxazin.

So pl. 128-129oC.

IR (nujol): 1715 cm-1.

NMR (DMSO-d6) : was 1.58 (6H, s), 3,86 (3H, s), 6,1 - of 6.17 (1H, m), 6,26 - 6,34 (1H, m), 7,14 (1H, d, J = 8,4 Hz), to 7.59 - the 7.65 (1H, m), 7,71 (1H, DD, J = 1,9 Hz and 8.4 Hz), 8,16 (1H, d, J = 1.9 Hz).

MASS (m/z): 258 (M++ 1).

Preparative example 50.

To a mixture of aluminum chloride (2.7 g), and 1,2-dichloroethane (10 ml) under cooling with ice, add acetic anhydride (1.3 ml) and the mixture is stirred for 20 minutes at the same temperature. To the mixture at 0-5oC added dropwise during 10 minutes to a mixture of methyl ester of 3-(pyrrol-1-yl)benzoic acid (2 g) and dichloroethane (3 ml) and the mixture is stirred for 3 hours at the same temperature. The reaction mixture was transferred into ice water and extracted with chloroform. The extract was washed with a saturated solution of sodium bicarbonate in water and water. The organic layer is dried over magnesium sulfate and after evaporation in vacuo get the ol): 1720, 1645 cm-1.

NMR (DMSO-d6) : to 2.42 (3H, s), 3,91 (3H, s), 6,64 and 6.7 (1H, m), 7,52 - 7,58 (1H, m), 7,68 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,92 (1H, d, J = 7.9 Hz), of 7.96 - of 8.04 (1H, m), 8,15 - 8,19 (1H, m), 8,31 - 8,35 (1H, m).

MASS (m/z: 244 (M++ 1).

Preparative example 51.

To a mixture of methyl ester of 3-(pyrrol-1-yl)benzoic acid (14 g) and pyridine (16,9 ml) in 1,2-dichloroethane (70 ml) under cooling with ice add trichloroethylene (15,5 ml) and the mixture is stirred for 7 days at room temperature. The mixture is transferred into chloroform with water and add with water and add 6 N. hydrochloric acid in a mixture of set pH 1. The separated organic layer was washed with saturated aqueous sodium bicarbonate and water. The mixture is dried over magnesium sulfate and evaporated in vacuum. Rinse residue diisopropyl ether get methyl ester 3-(2-trichloroacetonitrile-1-yl)benzoic acid (21,23 g).

So pl. 94-95oC.

IR (nujol): 1725, 1670, 1590 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 6,56 (1H, DD, J = 2,6 Hz, 4.3 Hz), 7,6-7,71 (4H, m), 7,82 (1H, c), 8,01 and 8.1 (1H, m).

MASS (m/z): 346 (M++ 1).

Preparative example 52.

To a solution of 5-(pyrrol-1-yl)-3-methoxycarbonylbenzyl acid (9,37 g) in tetrahydrofuran (100 ml) in atmospheres is of orformula (5,9 ml). Then the reaction mixture is stirred for 45 minutes at a temperature below -20oC. After that, the triethylamine hydrochloride is filtered off and washed with cold tetrahydrofuran, and the filtrate soon as possible adds to the intensively stirred suspension of sodium borohydride (4.35 g) in a mixture of tetrahydrofuran-water (8: 1, 80 ml). The stirring is continued for 5 hours at room temperature, after which the solution is acidified to pH 5. The tetrahydrofuran is removed under reduced pressure and the product extracted with ethyl acetate. An ethyl acetate extracts washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue is purified column chromatography on silica gel with elution by the mixture of chloroformmethanol (30:1). Eluruume fraction containing the target product, collect and evaporation in vacuo receive the methyl ester of 3-hydroxymethyl-5-(pyrrol-1-yl)benzoic acid (7,33 g).

So pl. 83-85oC.

IR (nujol): 3200, 1710, 1600 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, c), 4,63 (2H, d, J = 5.8 Hz), vs. 5.47 (1H, t, J = 5.8 Hz), 6,2 - 6,4 (2H, m), 7,3 - 7,5 (2H, m), 7,7 - 7,8 (3H, m).

MASS (m/z): 232 (M++ 1).

Preparative example 53.

To a solution of methyl ester of 3-hydroxymethyl-5-(pyrrol-1-yl)be amerivault 4.5 hours at 50oC. After cooling to room temperature the suspension is filtered and the filtrate evaporated in vacuum. The residue is purified column chromatography on silica gel with elution by the mixture hexane with ethyl acetate (10:1). Eluruume fraction containing the target product, collect and evaporation in vacuo receive in the form of oil methyl ester 3-methoxymethyl-5-(pyrrol-1-yl)benzoic acid (1,72 g).

IR (film): 2950, 1720, 1600 cm-1.

NMR (DMSO-d6) : at 3.35 (3H, s) of 3.9 (3H, s), of 4.54 (2H, s), 6,3 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,8 - 8 (3H, m).

MASS (m/z): 246 (M++ 1).

Preparative example 54.

To a solution of methyl ester of 3-hydroxymethyl-5-(pyrrol-1-yl)benzoic acid (4 g) in pyridine (40 ml) under cooling with ice, add acetic anhydride (4.9 ml). After stirring for 3 hours under ice cooling, the reaction mixture was transferred into ice water and extracted with diethyl ether. The ether extracts washed with water, 1 N. hydrochloric acid and brine, and dried over magnesium sulfate. The solvent is evaporated in vacuo and the residue purified column chromatography with elution by the mixture hexane-ethyl acetate (5:1). Eluruume fraction containing the target product, collect and evaporation in vacuo get methyl ether 3-ACE, 1600 cm-1.

NMR (DMSO-d6) : 2,11 (3H, c), a 3.9 (3H, c), 5,19 (2H, c), 6,3 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,8 - 8 (3H, m).

MASS (m/z): 274 (M++ 1).

Preparative example 55.

According to the method described in preparative examples 37 and 38, the following connections:

(1) Methyl ester 3-(2-cyanoprop-1-yl)benzoic acid.

So pl. 89-90oC.

IR (nujol): 2220, 1715, 1590 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), of 6.49 (1H, DD, J = 2,8 Hz, 3.9 Hz), 7,28 (1H, DD, J = 1.6 Hz, 3.9 Hz), the 7.65 (1H, DD, J = 1.6 Hz, 2.8 Hz), 7,76 (1H, DD, J = 8 Hz, 8 Hz), a 7.85 - a 7.92 (1H, m), 8.04 - 8,1 (2H, m).

MASS (m/z: 227 (M++ 1).

(2) Methyl ether 3-(2-cyano-5-methylpyrrole-1-yl)benzoic acid

So pl. 82-84oC.

IR (nujol): 2220, 1715 cm-1.

NMR (DMSO-d6) a 2.12 (3H, s) of 3.9 (3H, s), 6,21 (1H, d, J = 3,9 Hz), 7,11 (1H, d, J = 3,9 Hz), 7,7 - to 7.84 (2H, m), 7,92 - of 7.96 (1H, m), 8,09 - 8,17 (1H, m).

MASS (m/z): 241 (M++ 1).

(3) Methyl ester of 4-n-butyl-3-(2-cyanoprop-1-yl)benzoic acid

IR (film): 2230, 1725 cm-1.

NMR (DMSO-d6) : 0,76 (3H, t, J = 7.2 Hz), 1.04 million - of 1.27 (2H, m), of 1.27 to 1.47 (2H, m), 2,37 is 2.55 (2H, m), 3,88 (3H, s), 6,47 (1H, DD, J = 2.7 Hz, 4 Hz), 7,22 (1H, DD, J = 1.6 Hz, 4 Hz), the 7.43 (1H, DD, J = 1.6 Hz, 2.7 Hz), 7,66 (1H, d, J = 8.1 Hz), to 7.84 (1H, d, J = 1,8 Hz), 8,07 (1H, DD, J = 1,8 Hz, 8,1 Gogol): 2220, 1727 cm-1.

NMR (DMSO-d6) : of 3.94 (6H, s), 6.48 in - 6,54 (1H, m), 7,29 - 7,33 (1H, m), 7,72 - 7,76 (1H, m), with 8.33 (2H, s), 8,53 (1H, s).

Preparative example 56.

A mixture of dimethyl 5-(pyrrol-1-yl)isophthalic acid (80 g) and potassium hydroxide (20.2 g) in methanol (3.1 l) is stirred for 62 hours at 68oC. After cooling to room temperature the solvent is evaporated in vacuum. The residue is dissolved in water and the solution washed with ethyl acetate. The aqueous layer was acidified with hydrochloric acid (25,5 ml) and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuum and rinsing the residue with diethyl ether to obtain 3-methoxycarbonyl-5-(pyrrol-1-yl)benzoic acid (53,7 g).

So pl. 178 - 179oC.

IR (nujol): 3050, 1720, 1680 cm-1.

NMR (DMSO-d6) : 3,93 (3H, s), 6,3 - 6,4 (2H, m), and 7.5 and 7.6 (2H, m), 8,2 - 8,4 (3H, m) to 13.6 (1H, sh.C).

MASS (m/z: 244 (M++ 1).

Preparative example 57.

A mixture of dimethyl 5-(pyrrol-1-yl)isophthalic acid (1 g) and 4-(2-aminomethyl)of the research (0.65 g) is heated for 2 hours at 120oC. the Residue is purified column chromatography on silica gel (50 g) using as eluent a mixture of chloroform-metascore residue from a mixture of ethanol-ether obtained N-[2-(morpholine-4-yl)ethyl]-3-methoxycarbonyl-5-(pyrrol-1-yl)benzamide (353 mg).

So pl. 144 - 146oC.

IR (nujol): 3250, 1725, 1635, 1250, 720 cm-1.

NMR (DMSO-d6) : 2,3 - 2,6 (6H, m), 3,35 - 3,55 (2H, m), 3,55 to 3.7 (4H, m), 3,93 (3H, m), 6,3 - 6,4 (2H, m), 7,45 - of 7.55 (2H, m), 8,15 - of 8.27 (3H, m), 8,76 (1H, t, J = 5.6 Hz).

MASS (m/z): 358 (M+1).

Preparative example 58.

By the method similar to the method of preparative example 57, received the following connection:

N-[3-(morpholine-4-yl)propyl]-3-methoxycarbonyl-5-(pyrrol-1-yl)-benzamide

So pl. 126-127oC.

IR (nujol): 3250, 1730, 1635, 1250, 720 cm-1.

NMR (DMSO-d6) : 1,6 - 1,8 (2H, m), 2.3 to 2.4 (6H, m), 3,3 - 3,4 (2H, m), 3,5 - 3,6 (4H, m), 3,93 (3H, m), 6,32 to 6.35 (2H, m), 7,49 - 7,52 (2H, m), 8,15 - 8,17 (1H, m), 8,23 - of 8.28 (2H, m), 8,79 (1H, t, J = 5.4 Hz).

MASS (m/z): 372 (M+1).

Preparative example 59.

According to the methods similar to the methods of preparative examples 5 and 17, the following compounds:

(1) Methyl ester 2-methoxy-5-(pyrrol-1-yl)benzoic acid

So pl. 96 - 98oC.

IR (nujol): 1730 cm-1.

NMR (DMSO-d6) : is 3.82 (3H, s), 3,85 (3H, s), 6,2 - 6,28 (2H, m), 7.23 percent (1H, d, J = 9.1 Hz), 7,26 - 7,33 (2H, m), to 7.67 for 7.78 (2H, m).

(+) APCI MASS (m/z): 232/M+H/+.

Elemental analysis for C13H13NO3< / BR>
Calculated: C 67,52, H 5,67, N 6,06

Found">

IR (nujol): 3170, 1670, 1617 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 6,21 - 6,27 (2H, m), to 7.09 (1H, d, J = 8,8 Hz), 7.23 percent - 7,29 (2H, m), 7,73 (1H, DD, J = 2,8 Hz), 8,8 Hz), 7,81 (1H, d, J = 2,8 Hz), 10,4 (1H, s).

(+) APCI MASS (m/z): 218 /M+H/+.

Elemental analysis for C12H11NO3< / BR>
Calculated: C 66,35, H 5,10, N 6,45

Found: C 66,63, H 5,16, N 6,45

(3) Methyl ester of 2-nitro-5-(pyrrol-1-yl) benzoic acid

So pl. 86 - 87oC.

IR (nujol): 1727, 1585, 1325 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 6,36 - 6.42 per (2H, m), to 7.61 - in 7.7 (2H, m), 8,01 (1H, DD, J = 2,6 Hz and 8.9 Hz), of 8.06 (1H, d, J = 2.6 Hz), 8,23 (1H, d, J = 8,9 Hz).

Elemental analysis for C12H10N2O4< / BR>
Calculated: C 58,54, H 4.09 to, N 11,38

Found: C 58,66, H 3,90, N 11,21

(4) Methyl ester 5-(pyrrol-1-yl)-3-sulfamoylbenzoic acid

So pl. 178-179oC.

IR (nujol): 3310, 3220, 1702, 1605, 1350, 1168 cm-1.

NMR (DMSO-d6) : of 3.94 (3H, s), 6,34 - to 6.39 (2H, m), of 7.48 - rate of 7.54 (2H, m), and 7.6 (2H, c), 8,17 - of 8.28 (3H, s).

(5) Dimethyl 2-(pyrrol-1-yl)terephthalic acid

So pl. 55-57oC.

IR (nujol): 1715 (W.) cm-1.

NMR (DMSO-d6) : of 3.69 (3H, s), 3,91 (3H, s), 6,23 - of 6.29 (2H, m), 6,95 - 7,01 (2H, m), 7,88 (1H, d, J = 8.1 Hz), to $ 7.91 (1H, d, J = 1.6 Hz), 8.01 (1H, DD, J = 1.6 Hz, 8.1 Hz).

Elem) Methyl ether 4-acetamidomethyl-3-(pyrrol-1-yl)-benzoic acid

So pl. 135-137oC.

IR (nujol): 3280 (W.), 1730, 1630 cm-1.

NMR (DMSO-d6) : of 1.88 (3H, s), 3,86 (3H, s), 4,17 (2H, d, J=5.8 Hz) 6,24 - 6,03 (2H, m), 7-7,06 (2H, m), 7,55 (1H,d, J = 8,2 Hz), of 7.75 (1H, d, J = 1.7 Hz), of 7.97 (1H, DD, J = 1.7 Hz,8.2 Hz), scored 8.38 (1H, J = 5.8 Hz).

Elemental analysis for C15H16N2O3< / BR>
Calculated: C 66,16, H of 5.92, N 10,29

Found: C 66,35, H of 5.05, N 9,95

(7) Methyl ester of 2-(pyrrol-1-yl) isonicotinic acid

So pl. 51-53oC.

IR (guidal): 1724, 1605 cm-1< / BR>
NMR (DMSO-d6) : 3.94 (6.31 - 6,37 (3H, s), the 7.65 (1H, d, J = 5 Hz), 7,74 - 7,8 (2H, m), of 8.04 (1H, m), to 8.62 (1H, d, J = 5 Hz).

Elemental analysis for C11H10N2O2< / BR>
Calculated: C 65,34, H to 4.98, N 13,85

Found: C 65,24, H 4,74, N 13,59

(8) Methyl ester of 4-(pyrrol-1-yl) -2-carboxylic acid

So pl. 109-111oC.

IR (guidal): 3100, 1715, 1590 cm-1.

NMR (DMSO-d6) : to 3.92 (3H, s), 6,36 - 6,41 (2H, m), 7.68 per -7,74 (2H, m), 7,92 (1H, DD, J = 2,4 Hz, 5.5 Hz), 8,21 (1H, d, J = 2.4 Hz), 8,69 (1H, d, J = 5,5 Hz).

(+) APCI MASS (m/z: 203 /M+H/+.

(9) Methyl ester of 2-hydroxy-3-(pyrrol-1-yl)benzoic acid

So pl. 41-42oC.

IR (nujol): 1683 cm-1.

NMR (DMSO-d6) : 3,93 (3H, s), is 6.19 - of 6.26 (2H, m), 7,05 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,08 - 7,17 (2H, m), of 7.64 (1H, DD, who Inoi acid

IR (film): 3420, 1720, 1575 cm-1.

NMR (DMSO-d6) : a 3.87 (3H, s), of 4.44 (2H, d, J = 5.4 Hz), of 5.48 (1H, t, J = 5.4 Hz), 6,23 - of 6.29 (2H, m), 7-7,06 (2H, m), of 7.75 (1H, d, J = 1.7 Hz), 7,78 ( 1H, d, J = 8.1 Hz), 8 (1H, DD, J = 1.7 Hz, 8.1 Hz).

Preparative example 60.

By the method similar to the method of preparative example 34, received every two of the following stereoisomers:

(1) (A) Methyl ester 3-2-(E)-hydroxyimino)pyrrol-1-yl benzoic acid

So pl. 121-122oC.

IR (nujol): 1717 cm-.

NMR (DMSO-d6) : 2,1 (3H, s) of 3.9 (3H, s), is 6.54 (1H, DD, J = 1.6 Hz, 3 Hz), 7,44 - 7,49 (1H, m), 7,63 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,76 - 7,8 (1H, m), to 7.84 (1H, d, J = 7.9 Hz), 7,89 - to 7.93 (1H, m), of 8.09 (1H, d, and 1.6 Hz), 10,61 (1H, s).

Elemental analysis for C14H14N2O3< / BR>
Calculated: C 65,11, H 5,46, N 10,85

Found: C 65,26, H 5,54, N 10,78

(1) (b) Methyl ester of 3-[2-(Z)-hydroxyimino)pyrrol-1-yl] benzoic acid

So pl. 120-122oC.

IR (nujol): 1717 cm-1.

NMR (DMSO-d6) : 2,12 (3H, s) of 3.9 (3H, s), 6.75 in - 6,79 (1H, m), 7,46 - 7,51 (1H, m), of 7.64 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,84 - of 7.97 (2H, m), 8,03 - of 8.09 (2H, m), of 10.73 (1H, s).

Elemental analysis for C14H14N2O3< / BR>
Calculated: C 65,11, H 5,46, N 10,85

Found: C 64,72, H 5,17, N 10,59

(2) (A) Methyl ester of 3-(E)-2-labels is H, C) to 3.89 (3H, s), of 6.31 - 6,37 (1H, m), 6,68 - 6,74 (1H, m), 7,2 - of 7.25 (1H, m), of 7.64 - in 7.7 (2H, m), 7,82 - 7,87 (1H, m), 7,89 (1H, s), 7,95 - of 8.04 (1H, m).

(+) APCI MACC (m/z): 259 /M + H/+.

(2) (B) Methyl ester of 3-[(Z)-2-methoxyaminomethyl-1-yl)benzoic acid

IR (film): 1720, 1605 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s) to 3.92 (3H, s), 6,36 - 6.42 per (1H, m), 7,05 (1H, s), 7.18 in - 7,27 (1H, m), to 7.67 - 7,72 (2H, m), 7,81 - 7,86 (1H, m), 8,01 - 8,08 (1H, m).

(+) APCI MACC (m/z): 259 /M + H/+.

Preparative example 61.

A solution of methyl ester 3-(2-formylphenol-1-yl)benzoic acid (1 g) and benzyl(triphenylphosphonium)acetate (1.8 g) in tetrahydrofuran (10 ml), boiled for 30 hours. After evaporation of the solvent the residue is purified column chromatography on silica gel with elution with toluene. Containing the target product fractions are collected and their evaporation in vacuo receive in the form of oil methyl ester 3-[2-((E)-2-benzyloxycarbonylamino)pyrrol-1-yl)] benzoic acid (0,77 g).

IR (film): 1700 - 1725 (sh), 1620 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s) to 5.13 (2H, s), and 6.3 (1H, d, J = 15.7 Hz), 6,38 - 6,44 (1H, m), 7,09 - 7,28 (3H, m), 7,34 (5H, s), 7,65 - 7,8 (2H, m), 7,84 - 7,88 (1H, m), 8,04 - to 8.12 (1H, m).

Preparative example 62.

To a solution of methyl ester of 3-[2-((E)-2-benzyloxycarbonylamino)pyrrol-1-yl)] Ben is recovering at room temperature and atmospheric pressure. The catalyst was removed by filtration and the filtrate evaporated in vacuum. Rinse residue diisopropyl ether get methyl ether 3-2-(2-carboxyethyl)pyrrol-1-yl]benzoic acid (1,02 g).

So pl. 126-128oC.

IR (nujol): 1728, 1703 cm-1.

NMR (DMSO-d6) : of 2.45 (2H, t, J = 7 Hz), 2,73 (2H, t, J = 7 Hz), 3,88 (3H, s), 6 - 6,07 (1H, m), 6,11 - of 6.17 (1H, m), 6,67 - 6,92 (1H, m), 7,62 - 7,73 (2H, m), to 7.84 (1H, s), 7,95 - 8,02 (1H, m).

Preparative example 63.

To a solution of methyl ester 4-benzyloxycarbonyloxy-3- (pyrrol-1-yl)benzoic acid (5 g) in methanol (50 ml) and tetrahydrofuran (20 ml) is added 10% palladium on coal (0.5 g) and the mixture is subjected to catalytic recovery at room temperature and atmospheric pressure. The catalyst was removed by filtration and the filtrate evaporated in vacuum. To the residue is added a mixture of ethyl acetate with water and adding potassium carbonate in a mixture of set pH 8. In the separated aqueous layer by adding 6 N. hydrochloric acid to establish a pH 2 and the mixture extracted with ethyl acetate. The layer of the extract washed with brine, dried over magnesium sulfate and after evaporation in vacuo get methyl ester 4-carboxymethoxy-3-(pyrrol-1-yl)benzoic acid (and 2.26 g).

So pl. 98-102oC.

Preparative example 64.

By the method similar to the method of preparative example 4, obtained the following link:

Methyl ester of 5-amino-3-sulfamoylbenzoic acid

So pl. 163-165oC.

IR (nujol): 3480, 3380, 3280, 3220, 1700, 1330, 1165 cm-1.

NMR (DMSO-d6) : of 3.85 (3H, s), of 5.89 (2H, s), 7,2 - of 7.25 (1H, m), 7.3 to 7,37 (3H, m), 7.5 to at 7.55 (1H, m).

Preparative example 65.

A mixture of methyl ester of 5-cyano-3-(pyrrol-1-yl)benzoic acid (3 g), sodium azide (5.2 g) and ammonium chloride (4.3 g) in N,N-dimethylformamide (12 ml) is stirred for 4 hours at 120-125o. The mixture is transferred into ice-cold water (100 ml) and to this mixture sodium nitrite (5.5 g). The addition of 6 N. hydrochloric acid in a mixture of set pH 1 and the mixture is stirred for 30 minutes. The mixture is then extracted with ethyl acetate. The layer of the extract washed with brine and dried over magnesium sulfate. The solvent is removed by concentration and rinsing residue diisopropyl ether obtain methyl ester of 3-(pyrrol-1-yl)-5-(1H-tetrazol-5-yl)benzoic acid (3,35 g).

So pl. 217-218oC.

IR (nujol): 1720, 1600 cm-1.

NMR (DMSO-d6) : of 3.95 (3H, s), 6,35 is 6.4 (2H,th preparative method of example 65, received the following connection:

Methyl ester of 3-(1H-tetrazol-5-yl)benzoic acid

So pl. 178-179oC.

IR (nujol): 3159, 1692 cm-1.

NMR (DMSO-d6) : 3,93 (3H, s), 7,78 (1H, DD, J = 7.8 Hz, 7.8 Hz), 8,11 - 8,2 (1H, m), 8,28 is 8.38 (1H, m), 8,65 (1H, DD, J = 1.5 Hz, 1.5 Hz),

(-) APCI MACC (m/z): 203 /M-H/-.

Elemental analysis for C9H8N4O2< / BR>
Calculated: C 52,94, H 3,95, N 27,44

Found: C 52,61, H 3,81, N 27,49

Preparative example 67.

A mixture of methyl ester of 4-hydroxy-3-(pyrrol-1-yl)benzoic acid (1.5 g), 2-oxo-1,3-dioxolane (0,61 g) and tetraethylammonium (0,38 g) is heated for 3 hours at 140oC. the resulting mixture was dissolved in ethyl acetate solution in tetrahydrofuran. The solution is washed with water and dried over magnesium sulfate. Evaporation of the solvent to obtain the residue, which is purified column chromatography on silica gel with elution with a mixture of chloroform-ethyl acetate (9:1, about. /about.). Eluruume fraction containing the target product, collect and evaporation in vacuo receive in the form of oil methyl ester 4-(2-hydroxyethoxy)-3-(pyrrol-1-yl)benzoic acid (1.25 g).

IR (nujol): 3420, 1710, 1607 cm-1.

NMR (DMSO-d6) : 3,67 - 3,8 (2H, m), of 3.84 (3H, s), 4,19 (2H, t, J = 4,8 Hz) to 4.92 (1H, t, J = 5,M+H/+.

Preparative example 68.

By the method similar to the method of preparative example 67, received the following connection:

Methyl ester 3-(2-hydroxyethoxy)-5-vinylbenzoic acid

IR (pure): 3400, 1800, 1710, 1590 cm-1.

NMR (DMSO-d6) : 3,74 - 3,8 (2H, m) to 3.89 (3H, s), 3,97 - to 4.14 (2H, m), 4,9 - 4,96 (1H, m), 7,46 for 7.78 (8H, m).

(+) APCI MACC (m/z): 273 /M+H/+.

Preparative example 69.

To a mixture of methyl ester of 4-hydroxy-3-(pyrrol-1-yl)benzoic acid (5 g) and tert-butoxide potassium (2.7 g) in N,N-dimethylformamide (40 ml) under cooling with ice add benzylbromide (2,9 ml) and the mixture is stirred for 5 hours at room temperature. Then the reaction mixture is transferred into water and extracted with ethyl acetate. The layer of the extract washed with brine and dried over magnesium sulfate. The solvent is removed by concentration. The residue is crystallized from a mixture of toluene with diisopropyl ether to obtain methyl ester of 4-benzyloxy-3-(pyrrol-1-yl)benzoic acid (4.2-d).

So pl. 103-104oC.

IR (nujol): 1710, 1605 cm-1.

NMR (DMSO-d6) : of 3.84 (3H, s), 5,28 (2H, s), 6,18 - 6,24 (2H, m), 7,08 - to 7.15 (2H, m), 7,3 was 7.45 (6H, m), 7,83 (1H, d, J = 2.1 Hz), 7,92 (1H, DD, J = 2.1 Hz, 8.6 Hz).

Preparative Pius:

(1) Methyl ester of 4-methoxy-3-(pyrrol-1-yl)benzoic acid

So pl. 74-75oC.

IR (nujol): 1712, 1698, 1605 cm-1.

NMR (DMSO-d6) : 3,86 (3H, s) of 3.9 (3H, s), to 6.19 and 6.25 (2H, m), 7,05 and 7.1 (2H, m), 7,34 (1H, d, J = 8.7 Hz), and 7.8 (1H, d, J = 2.1 Hz), 7,94 (1H, DD, J = 2.1 Hz, 8.7 Hz).

Elemental analysis for C13H13NO3< / BR>
Calculated: C 67,52, H 5,67, N 6,04

Found: C 67,68, H of 5.82, N 6,05

(2) Methyl ether 4-benzyloxycarbonyloxy-3-(pyrrol-1 - yl)benzoic acid

IR (nujol): 1720 (sh), 1605 cm-1.

NMR (DMSO-d6) : of 3.85 (2H, s), a 5.1 (2H, s), 6,18 - 6,24 (2H, m), 7,14 - of 7.2 (2H, m), and 7.3 (1H, d, J = 8,9 Hz), 7,34 - 7,42 (5H, m), 7,81 - 7,9 (2H, m).

Preparative example 71.

By the method similar to the methods of preparative examples 37 and 38, the following connections:

(1) 8-Methoxycarbonyl-1-cyano-4,4-dimethyl-4H - pyrrolo-/2,1-C//1.4/benzoxazin

So pl. 114 - 116o.

IR (nujol): 2220, 1720 cm-1.

NMR (DMSO-d6) : of 1.62 (6H, s), 3,88 (3H, s), 6,44 (1H, d, J = 4 Hz), 7,26 (1H, d, J = 8.5 Hz), was 7.36 (1H, DD, J = 4 Hz, 8.7 Hz), 7,86 (1H, DD, J = 1.9 Hz, 8.5 Hz), 8,68 (1H, d, J = 1.9 Hz).

(2) Methyl ether 3-(2-cyanothiophene-3-yl)benzoic acid

So pl. 87-88oC.

IR (nujol): 2200, 1720, 740 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, >

Elemental analysis for C13H9NO2< / BR>
Calculated: C 64,18, H of 3.73, N 5,76

Found: C 64,16, H 3,50, N 5,67

(3) Methyl ester 3-(2-cianfuran-3-yl)benzoic acid

So pl. 114-115oC.

IR (nujol): 2220, 1500, 1420, 1260 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 7,37 (1H, d, J = 1.9 Hz), 7,72 (1H, DD, J = 7.8 Hz, 7.8 Hz), 8,01 - 8,08 (2H, m), and 8.2 (1H, d, J = 1.9 Hz), with 8.33 (1H, s).

(+) APCI MACC m/z): 228 /M+N/+.

(4) 4-Methoxycarbonyl-1-cyano-4E-pyrrolo/2,1-c//1.4/benzoxazin

So pl. 141-144oC.

IR (nujol): 2210, 1725 cm-1.

NMR (DMSO-d6) : of 3.84 (3H, s), from 5.29 (2H, s), 6,37 (1H, d, J = 4 Hz), 7,31 (1H, DD, J = 8 Hz, 8 Hz), was 7.36 (1H, d, J = 4 Hz), to 7.64 (1H, DD, J = 1.5 Hz, 8 Hz), 8,13 (1H, DD, J = 1.5 Hz, 8 Hz).

(+) APCI MACC m/z): 255 /M+N/+.

Preparative example 72.

By the method similar to the method of preparative example 41, received the following connection:

8-Methoxycarbonyl-1-dimethylaminomethyl-4,4-dimethyl-4H - pyrrolo-/2,1-c//1.4/benzoxazin

IR (film): 1715 (W.), 1610, 1590 cm-1.

NMR (DMSO-d6) : of 1.56 (6H, s) to 2.29 (6H, s) to 3.35 (2H, s), 3,85 (3H, s), the 6.06 (1H, d, J = 3.5 Hz), 6,21 (1H, d, J = 3.5 Hz), 7,14 (1H, d, J = 8,14 Hz), 7,73 (1H, DD, J = 2 Hz and 8.4 Hz), 8,91 (1H, d, J = 2 Hz).

(+) APCI MACC (m/z): 315 /M+N/+.

Preparative example 73.


So pl. 138-139oC.

IR (nujol): 3380, 3290, 1728, 1600, 1350, 1168 cm-1.

NMR (DMSO-d6) : of 3.94 (3H, s), 8,14 (2H, s), 8,68 (1H, d, J = 2.1 Hz), 8,73 (1H, d, J = 2.1 Hz).

(2) Methyl ether 3-(5-aminopyrrolo-1-yl)benzoic acid

So pl. 160-162oC.

IR (nujol): 3370, 3290, 3200, 1700, 1633 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 5,46 (2H, s) 5,52 (1H, d, J = 1,8 Hz), 7,34 (1H, d, J = 1,8 Hz), 7,63 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,83 - of 7.97 (2H, m), 8.17 - a 8,23 (1H, m).

(3) Methyl ester 3-(3-nitrophenyl)benzoic acid

So pl. 90-91oC.

IR (nujol): 1720, 1535, 1350 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), to 7.68 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,79 (1H, DD, J = 8 Hz, 8 Hz), 8 to 8.3 (5H, s), 8,44 (1H, DD, J = 2 Hz, 2 Hz).

(+) APCI MACC (m/z): 258 /M+N/+.

(4) Methyl ester 3-(2-chlorophenyl)benzoic acid

So pl. 46-48oC.

IR (nujol): 1720, 1300, 1240, 1110 cm-1.

NMR (DMSO-d6) : 3,88 (3H, s), 7,44 - of 7.48 (3H, m), 7,58 - 7,76 (3H, m), 7,98 - of 8.04 (2H, m).

(+) APCI MACC (m/z): 247 /M+N/+.

(5) Methyl ester 3-(3-forfinal)benzoic acid

IR (net): 1720, 1590, 1430, 1250, 1180 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 7,21 - 7,31 (1H, m), 7,52 - to 7.68 (4H, m), to 7.99 (2H, DDD, 8.0 Hz and 1.7 Hz, 1.7 Hz), 8,21 (1H, DD, J = 1.7 Hz, 1.7 Hz).

(+) APCI MACC (m/z): 231 /M+N/-1.

NMR (DMSO-d6) : of 3.9 (3H, s), 7,25 - 7,38 (2H, m), 7,66 (1H, DD, 7.5 Hz, 7.5 Hz), 7,71 - 7,8 (2H, m), to $ 7.91 - to 7.99 (2H, m), 8,17 (1H, DD, J = 1.7 Hz, 1.7 Hz).

(+) APCI MACC (m/z): 231 /M+N/+.

(7) Methyl ester 3-(3-triptoreline)benzoic acid

IR (net): 1720, 1440, 1330, 1280, 1240, 1110 cm-1.

NMR (DMSO-d6) : to 3.92 (3H, s), 7,62 - 7,81 (3H, m), 8 - - of 8.06 (4H, m), 8,23 (1H, DD, J = 1.7 Hz, 1.7 Hz).

(+) APCI MACC (m/z): 281 /M+N/+.

(8) Methyl ester 3-(3-chlorophenyl)benzoic acid

IR (net): 1720, 1590, 1560, 1300, 1240, 1110 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s) of 7.48 - EUR 7.57 (2H, m), to 7.59 - of 7.69 (2H, m), of 7.75 (1H, DD, J = 1.6 Hz, 1.6 Hz), 7.95 is shed 8.01 (2H, m), 8,19 (1H, DD, J = 1.6 Hz).

(+) APCI MACC (m/z): 247 /M+N/+.

(9) Methyl ester 3-(furan-3-yl)benzoic acid

IR (net): 1720, 1610, 1510, 1430, 1250 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s),? 7.04 baby mortality (1H, DD, J = 1.7 Hz, 0.9 Hz), 7,55 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,79 (1H, DD, J = 1.7 Hz, 1.7 Hz), 7,83 - 7,94 (2H, m), 8,16 (1H, DD, J = 1.7 Hz, 0.9 Hz), 8,32 (1H, s).

(+) APCI MACC (m/z): 203 /M+N/+.

(10) Methyl ester 3-(3-were)benzoic acid

IR (film): 1720, 1435, 1310, 1250 cm-1.

NMR (DMSO-d6) : 2,4 (3H, s) of 3.9 (3H, s), 7,2 - 7,26 (1H, m), 7,34 - the 7.65 (4H, m), 7,92 - 7,98 (2H, m), 8,16 - 8,19 (1H, m).

(11) Methyl EP (3H, C) of 7.3 to 7.7 (5H, m), 7,8 - - 8,12 (3H, m).

(+) APCI MACC (m/z): 231 /M+N/+.

Preparative example 74.

A solution of methyl ester 4-hydroxy-3-(pyrrol-1-yl)benzoic acid (15 g), pyridine (8,4 ml) and acetic anhydride (9.8 ml) in dichloromethane (75 ml) is stirred for 15 hours at room temperature. Then to the mixture is added a mixture of dichloromethane with water and adding 20% aqueous solution of potassium carbonate in a mixture of set pH 8. The separated organic layer is washed successively 1 N. hydrochloric acid and water. The organic layer is dried over magnesium sulfate and after evaporation in vacuo receive the methyl ester of 4-acetoxy-3-(pyrrol-1-yl)benainous acid (15.9 g).

IR (nujol): 1770, 1722 cm-1.

NMR (DMSO-d6) : 2,2 (3H, s) to 3.89 (3H, s), 6,25 of 6.31 (2H, m), 7,2 - was 7.08 (2H, m), and 7.5 (1H, DD, J = 9 Hz), 7,92 - 8,02 (2H, m).

Preparative example 75.

To a solution of phosphorus oxychloride (8,3 ml) and N,N-dimethylformamide (70 ml) is added at room temperature methyl ester of 4-acetoxy-3-(pyrrol-1-yl)benzoic acid (11.7 g) and the mixture is stirred for 20 hours at the same temperature. The reaction mixture is transferred into water and extracted with ethyl acetate. The layer of the extract washed with water, dried over magnesium sulfate and evaporated in HAC is the thief of sodium methoxide (9.7 ml) and the mixture is stirred for 30 minutes at the same temperature. After adding to the mixture of acetic acid (6 ml), the mixture is evaporated in vacuum. To the mixture are added ethyl acetate and water by adding 20% aqueous potassium carbonate in a mixture of set pH 7. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuum. Crystallized from toluene the residue is filtered and washing the precipitate with ether to obtain methyl ester of 3-(2-formylphenol-1-yl)-4-hydroxybenzoic acid (7,89 g).

So pl. 147-148oC.

IR (nujol): 1715, 1640, 1600 cm-1.

NMR (DMSO-d6) : 3,81 (3H, s), 6,4 - 6,46 (1H, m), 7,05 - to 7.2 (2H, m), 7,25 - 7,33 (1H, m), of 7.75 (1H, s), 7,83 - to 7.93 (1H, m), 9,01 (1H, s), 11,02 (1H, s).

Preparative example 76.

To a solution of methyl ester 3-(2-formylphenol-1-yl)-4-hydroxybenzoic acid (3 g) in tetrahydrofuran (30 ml) is added sodium borohydride (0,46 g) and the mixture is stirred for 1 hour at room temperature. The reaction mixture is transferred into a water-ethyl acetate and adding 6 N. hydrochloric acid to establish a pH of 7.5. The separated organic layer was washed with water, dried over magnesium sulfate and after evaporation in vacuo receive the methyl ester of 4-hydroxy-3-(2-hydroxymethylfurfural-1-yl) benzoic acid (2,54 g).

So pl. 152-153oC.

IR (Ni is 5 Hz ), 7,79 (1H, d, J = 2.1 Hz), the 7.85 (1H, d, J = 2.1 Hz, 8.5 Hz).

Preparative example 77.

To a cooled ice mixture of methyl ester of 4-hydroxy-3-(2-hydroxymethylfurfural-1-yl)benzoic acid (2.5 g) and triphenylphosphine (4 g) was added dropwise diethylazodicarboxylate (2.3 ml), after which the mixture is stirred for 2 hours at room temperature. The mixture is then transferred into water-ethyl acetate. The separated organic layer was washed with brine and dried over magnesium sulfate. Evaporation of the solvent to obtain the residue, which is purified column chromatography on silica gel with elution by chloroform. Eluruume fraction containing the target product, collect and evaporation in vacuo receive 8-methoxycarbonyl-4H-pyrrolo/2,1-c//1.4/benzoxazin (0,61 g).

So pl. 60-62oC.

IR (nujol): 1710 cm-1.

NMR (DMSO-d6) : a 3.87 (3H, s), of 5.26 (2H, s), between 6.08 - 6,14 (1H, m), 6,28 - 6,36 (1H, m), 7,18 (1H, d, J = 8.5 Hz ), to 7.61 - to 7.67 (1H, m), and 7.7 (1H, DD, J = 8,5 Hz, 8.5 Hz), 8,16 (1H, d, J = 2 Hz).

Elemental analysis for C13H11NO3< / BR>
Calculated: C 68,11, N 4,84, N 6,11

Found: C 67,83, H 4,92, N 6,12

Preparative example 78.

To a cooled ice mixture of pyrrole (2.3 ml) and 60% sodium hydride (1.3 g) in N,N-dimethylformamide (50 ml) was added marked the mixture is transferred into water and extracted with ethyl acetate. The layer of the extract washed with water, dried over magnesium sulfate and after evaporation receive in the form of oil methyl ester 3-(pyrrol-1-yl)methylbenzoic acid (4,14 g).

IR (film): 1715 cm-1.

NMR (DMSO-d6) : a 3.83 (3H, s), 5,19 (2H, s), 6,01 - the 6.06 (2H, m), for 6.81 - 6,86 (2H, m), 7,4 - 7,58 (2H, m), to 7.77 (1H, s), 7,86 (1H, d, J = 6,7 Hz).

Preparative example 79.

By the method similar to the method of preparative example 12, the following connection:

Methyl ester 3-(3-dimethylpropanoyl)benzoic acid

So pl. 70-73oC.

IR (nujol): 1720, 1630 cm-1.

NMR (DMSO-d6) : 2,95 (3H, s) 3,18 (3H, s) to 3.89 (3H, s), 5,86 (1H, d, J = and 12.2 Hz), and 7.6 (1H, DD, J = 7,7 Hz, 7.7 Hz), and 7.8 (1H, d, J, and 12.2 Hz), 8,02 - 8,11 (1H, m), 8,13 - 8,23 (1H, m), to 8.41 - 8,46 (1H, m).

Preparative example 80.

By the method similar to the method of preparative example 13, the following connection:

Methyl ester 3-(pyrazole-3-yl)benzoic acid.

So pl. 107-108oC.

IR (nujol): 3160, 1720 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 6,78 - 6,83 (1H, m), EUR 7.57 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,83 (1H, s), 7,89 (1H, d, J = 7,7 Hz), 8,08 (1H, d, J = 7,7 Hz), 8,42 (1H, s), 13,02 (1H, s).

Preparative example 81.

A mixture of methyl ester 3-(3-dimethylamino) in methanol (38 ml) is boiled with stirring for 64 hours. The solvent is removed by concentration and to the residue water is added. The addition of 20% aqueous solution of potassium carbonate in a mixture of set pH 9 and the mixture is extracted with ethyl acetate. The layer of the extract washed with brine, dried over magnesium sulfate and evaporated in vacuum. The remainder periostat from a solution of diisopropyl ether in n-hexane and filtering sediment obtain methyl ester of 3-(pyrimidine-4-yl)benzoic acid (0.8 g).

So pl. 69-71oC.

IR (nujol): 1722, 1580 cm-1.

NMR (DMSO-d6) : to 3.92 (3H, s), 7,73 (1H, d, J = 7.8 Hz, 7.8 Hz), 8,14 (1H, d, J = 7.8 Hz), and 8.2 (1H, d, J = 5.4 Hz), 8,48 (1H, d, J = 7.8 Hz), and 8.8 (1H, s), 8,93 (1H, d, J = 5.4 Hz), 9,31 (1H, s).

(+) APCI MACC (m/z): 215 /M+H/+.

Elemental analysis for C12H10N2O2< / BR>
Calculated: C 67,28, H 4,70, N 13,08

Found C 67,00, H 4,68, N 12,93

Preparative example 82.

By the method similar to the method of preparative example 18, the following compounds:

(1) 2-Chlorophenylhydrazone

So pl. 158-160oC.

IR (nujol): 3250, 1590 cm-1.

NMR (DMSO-d6) : 7,22 - the 7.43 (4H, m), 8,31 (2H, s).

(2) 3-Perfordiversified

So pl. 213-215oC.

IR (nujol): 1580, 1350, 1190 cm-1.


So pl. 254-256oC.

IR (nujol): 1600, 1400, 1220, 1150 cm-1.

NMR (DMSO-d6) : 7,06 - 7,26 (2H, m), 7,81 - 8,03 (2H, m).

(4) 3-Chlorophenylhydrazone

So pl. 177-179oC.

IR (nujol): 1590, 1410 cm-1.

NMR (DMSO-d6) : 7,33 is 7.5 (2H, m), 7,71 - to 7.84 (2H, m).

(5) 3-Shildiviaxave

So pl. 128-130oC.

IR (nujol): 3200, 1560, 1500, 1320 cm-1.

NMR (DMSO-d6) only 6.64 (1H, DD, J = 1.6 Hz, 0.6 Hz), a 7.62 (1H, DD, J = 1.6 Hz, 1.3 Hz), to 7.84 (1H, DD, J = 1.3 Hz, 0.6 Hz), to $ 7.91 (2H, s).

(6) 3-(4,4-Dimethyl-4,5-dihydrooxazolo-2-yl)phenyldimethylsilane

So pl. 105-107oC.

IR (nujol): 3300 (W.), 1640, 1360, 1180 cm-1.

NMR (DMSO-d6) : 1,3 (6H, s), 4,11 (2H, s), 7,39 - rate of 7.54 (1H, m), 7,82 is 8.38 (2H, m).

Preparative example 83.

By the method similar to the method of preparative example 20, the following connections:

(1) 3-(2-Chlorophenyl)benzoic acid

So pl. 185-187oC.

IR (nujol): 1670, 1320, 1250 cm-1.

NMR (DMSO-d6) : 7,44 - of 7.48 (3H, m), EUR 7.57 - 7,73 (3H, m), 7,98 - 8,03 (2H, m), 13,16 (1H, sh.S.).

(-) APCI MACC (m/z): 231 /M-H/-.

(2) 3-(3-Forfinal)benzoic acid

So pl. 145-147oC.

IR (nujol): 1680, 1580, 1320, 1260 cmSS="ptx2">

(+) APCI MACC (m/z): 217 /M+H/+.

(3) 3-(4-Forfinal)benzoic acid

So pl. 181-183oC.

IR (nujol): 1690, 1310, 1230 cm-1.

NMR (DMSO-d6) : 7,27 - 7,38 (2H, m), and 7.6 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,71 - 7,8 (2H, m), 7,88 - of 7.97 (2H, m), 8,16 (1H, DD, J = 1.6 Hz, 1.6 Hz), 13,12 (1H, s).

(-) APCI MACC (m/z): 215 /M-H/-.

(4) 3-(3-Triptoreline)benzoic acid

So pl. 138-140oC.

IR (nujol): 1680, 1340, 1120 cm-1.

NMR (DMSO-d6) : to 7.59 (1H, DD, J = 7,7 Hz, 7.7 Hz), to 7.67 - 7,79 (2H, m), 7,9 - 8,04 (4H, m), of 8.28 (1H, s).

(-) APCI MACC (m/z): 264 /M-H/-.

(5) 3-(3-Chlorophenyl)benzoic acid

So pl. 178-180oC.

IR (nujol): 1680, 1310, 1250 cm-1.

NMR (DMSO-d6) : of 7.48 - 7,71 (4H, m), to 7.77 (1H, DD, J = 1.9 Hz, 1.9 Hz), 7,94 shed 8.01 (1H, DD, J = 1,8 Hz, 1.8 Hz).

(-) APCI MACC (m/z): 231 /M-H/-.

(6) 3-(Furan-3-yl)benzoic acid

So pl. 145-147oC.

IR (nujol): 1680, 1580, 1370, 1290 cm-1.

NMR (DMSO-d6) : 7,03 (1H, DD, J = 1.6 Hz, 1.6 Hz), 7,53 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,79 (1H, DD, J = 1.6 Hz, 1.6 Hz), 7,83 - to $ 7.91 (2H, m), 8,16 (1H, DD, J = 1.6 Hz, 1 Hz), 8,31 (1H, s), 13,07 (1H, s).

(+) APCI MACC (m/z): 189 /M+H/+.

(7) 3-(2-Forfinal)benzoic acid

So pl. 144-146oC.

IR (nujol): 1680, 1250, 745 cm
So pl. 123o-125oC.

IR (nujol): 1680, 1305, 1280, 750 cm-1.

NMR (DMSO-d6) : 2,4 (3H, s), 7,2 - the 7.65 (5H, m), 7,88 - of 7.97 (2H, m), 8,16 - 8,19 (1H, m), to 13.09 (1H, s).

Preparative example 84.

By the method similar to the method of preparative example 26, the following connections:

(1) Methyl ester 3-(pyridin-2-yl)benzoic acid

IR (film): 1720, 1580 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 7,41 - 7,47 (H, m), 7,66 (1H, DD, J = 7,6 Hz and 7.6 Hz), to $ 7.91 - 8,03 (1H, m), 8 and 8.1 (2H, m), 8,3 an 8.4 (1H, m), 8,69 - 8,76 (2H, m).

(+) APCI MACC (m/z): 214 /M+H/+.

(2) Methyl ether 3-(pyridin-3-yl)benzoic acid

IR (film): 1720, 1580 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 7,47 - 7,58 (1H, m), 7,68 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,97 - 8,07 (2H, m), 8,08 - 8,18 (1H, m), 8,23 (1H, d, J = 1.6 Hz, 1.6 Hz), 8,63 (1H, d, J = 1.6 Hz, 4.8 Hz), 8,93 (1H, DD, J = 0.7 Hz, 2.4 Hz).

(+) APCI MACC (m/z): 214 /M+H/+.

(3) Dimethyl 5-[2-(4,4-dimethyl-4,5-dihydrooxazolo-2 - yl)phenyl] isophthalic acid

So pl. 89-90oC.

IR (nujol): 1725, 1660, 1235 cm-1.

NMR (DMSO-d6) : to 1.15 (6H, s), 3,81 (2H, s), 3,91 (6H, s), 7,49 - 7,76 (4H, m), 8,14 (2H, s), 8,46 (1H, s).

(+) APCI MACC (m/z): 368 /M+H/+.

(4) 4,4-Dimethyl-2-[3-(2-nitrophenyl)phenyl]4,5-dihydrooxazolo

IN, DDD, J = 7,1 Hz, 1.7 Hz), of 8.04 (1H, d, J = 7.9 Hz, 1.3 Hz).

(+) APCI MACC (m/z): 297 /M+H/+.

(5) Methyl ether 3-3-(4,4-dimethyl-4,5 - dihydrooxazolo-2-yl)phenyl benzoic acid

So pl. 53-55oC.

IR (net): 2950, 1720, 1650, 1440, 1300 cm-1.

NMR (DMSO-d6) : of 1.32 (6H, s), 3,91 (3H, s) to 4.15 (2H, s), to 7.61 (1H, DD, J = 1.7 Hz, 7.7 Hz), 7,66 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,86 - a 7.92 (2H, s), 7,97 - 8,03 (2H, m), 8,11 (1H, DD, J = 1.6 Hz, 1.6 Hz), 8,19 (1H, d, 1.7 Hz, 1.7 Hz).

(+) APCI MACC (m/z): 310 /M+H/+.

Elemental analysis for C19H19NO3< / BR>
Calculated: C 73,77, H is 6.19, N 4,53

Found: C 73,89, H 6,40, N 4,34

Preparative example 85.

By the method similar to the method of preparative example 28, the following compounds:

(1) Dimethyl 5-(2-cyanophenyl)isophthalic acid

So pl. 185-187oC.

IR (nujol): 2225, 1720, 1240, 990, 755 cm-1.

NMR (DMSO-d6) : of 3.94 (6H, s), 7,63 - 7,9 (4H, m), 8,01 (1H, d, J = 7.8 Hz), of 8.37 (2H, s), 8,58 (1H, s).

(+) APCI MACC (m/z): 296 /M+H/+.

(2) Methyl ether 3-(3-cyanophenyl) benzoic acid

So pl. 82-84oC.

IR (nujol): 2230, 1720, 1250 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s), to 7.67 (1H, DD, J = 7,6 Hz and 7.6 Hz), and 7.7 (1H, DD, J = 7,6 Hz and 7.6 Hz), 7,89 (1H, DDD, J = 7,6 Hz, 1.4 Hz, 1.4 Hz), 7,98 - 8,SUB>2< / BR>
Calculated: C 75,94, H 4,67, N 5,90

Found: C 75,91, H 4,74, N OF 5.89

Preparative example 86.

By the method similar to the method of preparative example 30, the following connection:

Methyl 3-dimethylcarbamoyl-5-(pyrrol-1-yl)benzoate

IR (film): 3450, 3130, 2950, 1720, 1630 cm-1.

NMR (DMSO-d6) : of 2.93 (3H, s), to 3.02 (3H, s), 3,91 (3H, s), 6,3 - 6,4 (2H, m), and 7.5 and 7.6 (2H, m), 7,7 - 7,8 (1H, m), 7,9 - 8 (1H, m), of 8.1 to 8.2 (1H, m).

(+) APCI MACC (m/z): 273 /M+H/+.

Preparative example 87.

To a mixture of hydroxylamine hydrochloride (0,61 g) and 28% methanolic solution of sodium methoxide (1.8 ml) in methanol (20 ml) is added methyl ether 3-formyl-5-(pyrrol-1-yl)benzoic acid (2 g) and all is stirred for 22 hours at room temperature. The reaction mixture is transferred into a water-ethyl acetate. The organic layer is successively washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuo and the residue purified column chromatography on silica gel with elution with a mixture of chloroform-ethyl acetate (20: 1). Eluruume fraction containing the target product, collect and evaporation in vacuo get methyl ether 3-gidroksilaminami-5-(pyrrol-1-yl)benzoic acid (1,69 g).

So pl. 154-155oC.

<59 (1H, C).

(+) APCI MACC (m/z): 245 /M+H/+.

Elemental analysis for C13H12N2O3< / BR>
Calculated: C 63,93, H 4,95, N 11,47

Found: C 64,02, H 5,15, N 11,46

Preparative example 88.

By the method similar to the method of preparative example 52, received the following connection:

Methyl ester of 3-hydroxymethyl-5-vinylbenzoic acid

So pl. 89-90oC.

IR (nujol): 3475, 1720, 1250, 760 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s) and 4.65 (2H, q, j 5.8 Hz), 5,43 (1H, t, J = 5.8 Hz), 7,37 - of 7.55 (3H, m), to 7.67 - 7,72 (2H, m), 7,87 (1H, s), 7,95 (1H, s), with 8.05 (1H, s).

(+) APCI MACC (m/z): 243 /M+H/+.

Preparative example 89.

By the method similar to the preparative method of example 86, received the following connection:

3-Methoxycarbonyl-5-phenylbutane acid

So pl. 170-172oC.

IR (nujol): 1720, 1685, 750 cm-1.

NMR (DMSO-d6) : 3,93 (3H, s), 7,4 - 7,6 (3H, m), 7,7 - 7,8 (2H, m), scored 8.38 - to 8.41 (2H, m), of 8.47 (1H, s), 13,44 (1H, s).

(+) APCI MACC (m/z): 257 /M+H/+.

Preparative example 90.

A mixture of 3-hydrazinobenzene acid (5 g) and ethyl ester of 2-ethoxymethylene-2-tsianuksusnogo acid (5.6 g) in ethanol (50 ml) is boiled with stirring for 2 hours, after which the mixture is evaporated in MESI set pH 8. In the separated aqueous layer by adding 6 N. hydrochloric acid set pH 4 and then extracted with ethyl acetate. The layer of the extract washed with water, dried over magnesium sulfate and evaporated in vacuum. Sediment periostat from a mixture of ethyl acetate-diisopropyl ether and filtration of the precipitate obtained 3-(5-amino-4-ethoxycarbonylmethyl-1-yl)benzoic acid (6 g).

So pl. 172-174oC.

IR (nujol): 3360, 3250, 1688, 1605 cm-1.

NMR (DMSO-d6) : of 1.28 (3H, t, J = 7,1 Hz) to 4.23 (2H, K, J = 7,1 Hz), 6,46 (2H, s), to 7.67 (1H, DD, J = 7.8 Hz, 7.8 Hz), of 7.75 (1H, h), 7,81 (1H, t, J = 7.8 Hz), of 7.96 (1H, d, J = 7.8 Hz), 8,08 (1H, s), of 13.27 (1H, s).

Preparative example 91.

A mixture of 3-(5-amino-4-ethoxycarbonylmethyl-1-yl)benzoic acid (5.9 g) and sodium hydroxide (2.1 g) in water (15 ml) is stirred for 2 hours at 80oC. To the reaction mixture are added water and add 6 N. hydrochloric acid in a mixture establish a pH of 3.5. The formed precipitate is filtered off, washed with water and after drying, the obtained 3-(5-amino-4-carboxybenzoyl-1-yl)benzoic acid (5.1 g).

So pl. 194-196oC.

IR (nujol): 3540, 3420, 3200, 1678 cm-1.

NMR (DMSO-d6) : 6,41 (2H, s), 7,66 (1H, t, J = 7.8 Hz, 7.8 Hz), 7,72 (1H, s), 7,82 (1H, d, J = 7.8 Hz), 7,95 (1H, d, J = 7.8 Hz), 8,08 (1H, s), 12,88 (1H, s).

ml) is boiled for 6 hours. To the mixture are added ethyl acetate and water by adding 20% aqueous solution of potassium carbonate in a mixture of set pH 9. Added to separate the aqueous layer 6 N. hydrochloric acid in it set pH 3.5, and the mixture is extracted with a solution of ethyl acetate in tetrahydrofurane. The layer of the extract washed with brine, dried over magnesium sulfate and evaporation in vacuo receive 3-(5-aminopyrazole-1-yl)benzoic acid (to 7.59 g).

So pl. 155-156oC.

IR (nujol): 3300, 3210, 1700, 1635 cm-1.

NMR (DMSO-d6) : 5,43 (2H, s), the 5.51 (1H, d, J = 1,8 Hz), 7,33 (1H, d, J = 1,8 Hz), and 7.6 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,82 - to $ 7.91 (2H, m), 8,15 - 8,21 (1H, m), 13,15 (1H, s).

(+) APCI MACC (m/z): 204 /M+H/+.

Preparative example 93.

To a solution of dimethyl ester of terephthalic acid (10 g) in acetonitrile (90 ml) at room temperature add tert-piperonyl potassium (6.4 g) and the mixture is stirred for 1 hour at 60-64oC. the Reaction mixture is transferred into a solution of conc. hydrochloric acid (4,7 ml) in water (150 ml) and extracted with ethyl acetate. The layer of the extract washed with water and dried over magnesium sulfate. Evaporation of the solvent to obtain the residue, which is purified column chromatography on silica gel with elution by chloroform. Eluruume fractions containing the,72 g).

So pl. 48-52oC.

IR (nujol): 2250, 1723, 1693, 1600 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), is 4.85 (2H, s), 7,73 1H, DD, J = 7,6 Hz and 7.6 Hz), 8,1 - 8,32 (2H, m), 8,43 (1H, s).

Preparative example 94.

To a stirred mixture of methyl ester 3-(cyanoacetyl)benzoic acid (2 g), triethylamine (1.4 ml), triethylamine hydrochloride (1.4 g) and 40% aqueous solution of methylamine (0,93 ml) at room temperature add chloroacetone (0,86 ml) and the mixture is stirred for 2 hours at the same temperature. To the reaction mixture are added ethyl acetate and the mixture washed with water. The organic layer is dried over magnesium sulfate and evaporated in vacuum. By recrystallization of the residue from ethanol methyl ester 3-(3-cyano-1,5-dimethylpyrrole-2-yl)benzoic acid (1.6 g).

So pl. 125-126oC.

IR (nujol): 2220, 1720 cm-1.

NMR (DMSO-d6) : of 2.26 (3H, s), 3,47 (3H, s) to 3.89 (3H, s), 6,37 (1H, s) of 7.64 - of 7.82 (2H, m), 8 (1H, s), 8,02 shed 8.01 (1H, m).

(+) APCI MACC (m/z): 255 /M+H/+.

Preparative example 95.

To a solution of dimethyl 5-hydroxyisophthalic acid (5 g), 4-dimethylaminopyridine (0.45 g) and 2,6-lutidine in dichloromethane (60 ml) was added dropwise at -30oC bis(triftormetilfullerenov)anhydride (4.8 ml). At the room temperature. To the reaction mixture was added saturated aqueous solution of ammonium chloride, the aqueous layer was separated and twice extracted with methylene chloride. The combined extracts are dried over magnesium sulfate and evaporated in vacuum. The residue is dissolved in ethyl acetate and washed successively with water, 10% hydrochloric acid, saturated sodium bicarbonate solution, brine and dried over magnesium sulfate. The solvent is removed in vacuo and crystallization of the residue from n-hexane and diethyl ether to obtain dimethyl 5-(tripterocalyx)isophthalic acid (5.59 in).

So pl. 73-74oC.

IR (nujol): 1725, 1135, 990 cm-1.

NMR (DMSO-d6) : of 3.94 (6H, s), of 8.27 (2H, s), charged 8.52 (1H, s).

(+) APCI MACC (m/z): 343 /M+H/+.

Preparative example 96.

By the method similar to the method of preparative example 95, received the following connection:

Methyl ester of 5-Benzyloxy-3-(tripterocalyx)- benzoic acid

IR (net): 1720, 1580, 1300, 1220, 1130 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), of 5.26 (2H, s), 7,31 - EUR 7.57 (7H, m), of 7.64 - 7,66 (1H, m).

(+) APCI MACC (m/z): 391 /M+H/+.

Preparative example 97.

A mixture of dimethyl 5-(cryptomelane the l) is stirred for 3 hours at 100oC in nitrogen atmosphere. After evaporation of the solvent the residue is dissolved in a mixture of dichloromethane (100 ml) with water. The organic layer is successively washed with aqueous 10% sodium carbonate solution and brine, dried over magnesium sulfate and evaporated in vacuum. Crystallization of the residue from hexane receive dimethyl 5-phenylazophenol acid.

So pl. 91-92oC.

IR (nujol): 1730, 1235, 745 cm-1.

NMR (DMSO-d6) : 3,93 (6H, s), 7,4 - 7,6 (3H, m), 7,7 - 7,8 (2H, m), 8,39 (2H, s), 8,44 (1H, s).

(+) APCI MACC (m/z): 271 /M+H/+.

Preparative example 98.

By the method similar to the preparative method of example 97, received the following connection:

Methyl ester of 3-benzyloxy-5-vinylbenzoic acid.

So pl. 83-84oC.

IR (nujol): 1720, 1590, 1340, 1240 cm-1.

NMR (DMSO-d6) : 3,88 (3H, s), at 5.27 (2H, s), 7,32 and 7.6 (10H, m), of 7.69 (1H, DD, J = 1.4 Hz and 1.4 Hz), 7,73 (1H, DD, J = 1.4 Hz and 1.4 Hz), and 7.8 (1H, DD, J = 1.4 Hz and 1.4 Hz).

(+) APCI MACC (m/z): 319 /M+H/+.

Preparative example 99.

To a solution of methyl ester 3-(3-nitrophenyl)benzoic acid (2 g) in methanol (30 ml) is added 10% palladium on coal (0.4 g) and the mixture is subjected to catalytic recovery kamaryut in vacuum. Crystallization of the residue from diethyl ether to obtain methyl ester 3-(3-AMINOPHENYL)benzoic acid (1.45 g).

So pl. 63-65oC.

IR (nujol): 3400, 1705, 1220, 755 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, s), 6,6 - 6,66 (1H, m), 6,8 - 6,95 (2H, m), to 7.15 (1H, DD, J = 7.8 Hz, 7.8 Hz), to 7.59 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,8 - of 7.95 (2H, m), 8,1 - 8,13 (1H, m).

Preparative example 100.

4,4-Dimethyl-2-[3-(2-nitrophenyl)phenyl]-4,5-dihydrooxazolo (1.7 g) is boiled in 95% methanol solution of sulfuric acid (prepared by mixing methanol (15 ml), concentrated sulfuric acid (1,15 ml) and water (1,44 ml) and bringing the total volume to 28.7 ml by adding additional quantities of methanol). After cooling, the solution is concentrated to about 7 ml and transferred into the ether (60 ml). The ether solution is washed with aqueous potassium carbonate solution and brine, dried over magnesium sulfate and concentration in vacuo get methyl ester 3-(2-nitrophenyl)benzoic acid as a yellow solid.

So pl. 88-90oC.

IR (nujol): 1720, 1520 cm-1.

NMR (DMSO-d6) : 3,88 (3H, s), 7,58 - of 7.82 (5H, m), 7,89 (1H, s), 8 - of 8.04 (2H, m).

(+) APCI MACC (m/z): 258 /M+H/+.

Preparative example 101.

According to the technique, Ana is arbonyl)phenyl benzoic acid.

So pl. 99-101oC.

IR (nujol): 1730, 1320, 1260, 1240 cm-1.

NMR (DMSO-d6) : 3,91 (6H, s), 7,66 (2H, DD, J = 7.8 Hz, 7.8 Hz), 8,01 (4H, DD, J = 7.8 Hz, 1.8 Hz), and 8.2 (2H, DD, J = 1.6 Hz, 1.6 Hz).

(+) APCI MACC (m/z): 271 /M+H/+.

Preparative example 102.

To a solution of methyl ester of 3-benzyloxy-5-vinylbenzoic acid (10 g) in acetic acid (300 ml) is added 10% palladium on coal (1 g) and the mixture is subjected to catalytic hydrogenation at 80oC and atmospheric pressure. The catalyst was removed by filtration and the filtrate evaporated in vacuum. To the residue is added ethyl acetate and water and adding potassium carbonate establish a pH of 5. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporation in vacuo receive the methyl ester of 3-hydroxy-5-vinylbenzoic acid.

So pl. 108-110oC.

IR (nujol): 3400, 1710, 1590, 1350, 1250 cm-1.

NMR (DMSO-d6) : a 3.87 (3H, s), 7,29 (1H, DD, J = 1.7 Hz, 1.7 Hz), of 7.36 - rate of 7.54 (4H, m), 7,62 - to 7.67 (3H, m), of 10.05 (1H, s).

(+) APCI MACC (m/z): 229 /M+H/+.

Preparative example 103.

A mixture of methyl ester of 3-hydroxymethyl-5-(pyrrol-1-yl)benzoic acid (20 g) and manganese dioxide (100 g) in dichloromethane (0.5 l) is stirred for 22 hours at the in diisopropyl ether and petroleum ether to obtain methyl ester of 3-formyl-5-(pyrrol-1-yl)benzoic acid (17.6 g).

So pl. 85-86oC.

IR (nujol): 1710, 1600 cm-1.

NMR (DMSO-d6) : of 3.94 (3H, s), 6,3 - 6,4 (2H, m), and 7.5 and 7.6 (2H, m), 8,2 - 8,4 (3H, m), 10,12 (1H, s).

(+) APCI MACC (m/z): 230 /M+H/+.

Preparative example 104.

In a cooled ice mixture methyl ester 3-amino-5-(pyrrol-1-yl)benzoic acid (1 g) and pyridine (0,41 ml) in dichloromethane (20 ml) add bromoacetamide (of 0.44 ml). After stirring 6 hours at room temperature the reaction mixture is transferred into a mixture of ethyl acetate with ice water. The organic layer is successively washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuum and the grinding of the residue in diethyl ether to obtain methyl ester of 3-(bromoacetamide-5-(pyrrol-1-yl)benzoic acid (1.51 g).

So pl. 154 - 157oC

IR (nujol): 3250, 1715, 1650, 1600 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s), 4.09 to (2H, s), 6,3 - 6,4 (2H, m), 7.3 to 7.4 (2H, m), 7,7 - 7,8 (1H, m), 8 and 8.1 (2H, m), 10,78 (1H, s).

(+) APCI MACC (m/z): 337, 339 /M+H/+< / BR>
Preparative example 105.

A mixture of methyl ester of 3-bromoacetamide-5-(pyrrol-1-yl)benzoic acid (0.5 g) and the research (and 0.28 ml) in dichloromethane (5 ml) and tetrahydrofuran (7 ml) is stirred for 17 hours at room temperature. Then Ryo and dried over magnesium sulfate. The solvent is evaporated in vacuo and the residue purified column chromatography on silica gel with elution by chloroform. Eluruume fraction containing the target product, collect and evaporation in vacuo get methyl ether 3-morpholinosydnonimine-5-(pyrrol-1-yl)benzoic acid (0,48 g). So pl. 108-109oC.

IR (nujol): 1725, 1690, 1605 cm-1.

NMR (DMSO-d6) : 2,4-2,6 (4H, m), 3,18 (2H, s), 3,6 - 3,8 (4H, m) to 3.89 (3H, s), 6,3 - 6,4 (2H, m), 7,2 - 7,3 (2H, m), 7,7 - 7,8 (1H, m), 8,1 - 8,3 (2H, m), 10,08 (1H, s).

(+) APCI MACC (m/z): 344 /M+H/+< / BR>
Preparative example 106.

By the method similar to the preparative method of example 105, obtained the following link:

Methyl ether 3-diethylaminoethylamine-5-(pyrrol-1-yl)-benzoic acid

So pl. 103-105oC.

IR (nujol): 3250, 2960, 1720, 1685, 1600 cm-1.

NMR (DMSO-d6) : of 1.03 (6H, t, J = 7,1 Hz), 2,62 (4H, K, J = 7,1 Hz), 3,19 (2H, s) to 3.89 (2H, s), 6,2 - 6,4 (2H, m), 7.3 to 7.4 (2H, m), 7,73 (1H, s), 8,13 (1H, s), 8,31 (1H, s), of 10.01 (1H, s).

(+) APCI MACC (m/z): 330 /N+H/+.

Preparative example 107.

To a mixture of methyl ester of 3-amino-5-(pyrrol-1-yl)benzoic acid (2 g) and triethylamine (1.4 ml) in dichloromethane (130 ml) at -78oC add bis(triftormetilfullerenov)anhydride (1.7 ml). Rea. the content of inorganic fillers layer successively washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuum and the grinding of the residue in petroleum ether to obtain methyl ester of 3-triftormetilfullerenov-5-(pyrrol-1-yl)benzoic acid (3,17 g).

So pl. 147-148oC.

IR (nujol): 3150, 1705, 1600 cm-1< / BR>
NMR (DMSO-d6): : 3,91 (3H, s), 6,3-6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,6 - 8 (3H, s).

(+) APCI MACC (m/z): 349 /M+H/+.

Preparative example 108.

By the method similar to the method of preparative example 107 obtained the following link:

Methyl ester 3-(3-triftormetilfullerenov)-benzoic acid

So pl. 103 - 104oC

IR (nujol): 3200, 1705, 960, 750 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s), 7,31 and 7.36 (1H, m), 7.5 to 7,72 (4H, m), 7,9 - with 8.05 (2H, m), 8,14 - 8,17 (1H, m)

(+) APCI MACC (m/z): 360 /M+H/+.

Preparative example 109.

A mixture of methyl ester of 3-formyl-5-(pyrrol-1-yl)benzoic acid (3 g), malonic acid (2,73 g), piperidine (0.3 ml) and pyridine (30 ml) is stirred for 1 hour at 80oC. After cooling to room temperature the reaction mixture is transferred into the water. The solution is acidified to pH 1 and extracted with ethyl acetate. The extract is washed with water and R is afia on silica gel with elution with a mixture of chloroform-methanol (15:1). Eluruume fraction containing the target product, collect and evaporation in vacuo receive the methyl ester of 3-[(E)-2-carboxyethyl]-5-(pyrrol-1-yl)benzoic acid (2,43 g).

So pl. 210 - 211oC.

IR (nujol): 1720, 1630, 1590 cm-1.

NMR (DMSO-d6) : of 3.9 (3H, s), 6,3 - 6,4 (2H, m), for 6.81 (1H, d, J = 16 Hz), and 7.5 and 7.6 (2H, m), the 7.65 (1H, d, J = 16 Hz), of 7.9 to 8.3 (3H, m)

(+) APCI MACC (m/z): 272 /M+H/+.

Preparative example 110.

To a mixture of methyl ester of 3-[(E)-carboxyethyl]-5-(pyrrol-1-yl)benzoic acid (1.9 g) and Nickel chloride (11) in methanol (40 ml) is added in portions sodium borohydride (1.24 g). After stirring for 7 hours at room temperature the reaction mixture is filtered and transferred into water, followed by acidification to pH 2. The formed precipitate is filtered off and, after washing with water to obtain methyl ester of 3-(2-carboxyethyl)-5-(pyrrol-1-yl)benzoic acid (1,72 g).

So pl. 129 - 130oC.

IR (nujol): 1720, 1700, 1600 cm-1.

NMR (DMSO-d6) : of 2.64 (2H, t, J = 7.4 Hz), 2,95 (2H, t, J = 7.4 Hz), 3,88 (3H, s), 6,3 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,7 - 7,9 (3H, m), 12,19 (1H,sh.C).

(+) APCI MACC (m/z): 274 /M+H/+.

Elemental analysis for C15H15NO4< / BR>
Calculated: C 65,93, H of 5.53, N 5,13

Found: C 65,88, the notes (3 g), malonic acid (2.7 g), pyridine (30 ml) and piperidine (0.3 ml) is stirred for 3 hours at 90-100oC. the Reaction mixture is transferred into the water and add 6 N. hydrochloric acid, the mixture is acidified to pH 1. The mixture is then extracted with a mixture of ethyl acetate with tetrahydrofuran. The layer of the extract washed with brine, dried over magnesium sulfate and evaporated in vacuum. By recrystallization of the residue from ethanol methyl ether -3[2-((E)-2-carboxyethyl)pyrrol-1-yl] benzoic acid.

So pl. 201 - 203oC.

IR (nujol): 1728, 1673, 1610 cm-1.

NMR (DMSO-d6) : the 3.89 (3H, c), 6,12 (1H, d, J = 15.7 Hz), 6,35 - to 6.39 (1H, m), 7? 7.04 baby mortality (1H, m), 7,17 (1H, d, J = 15.7 Hz), 7,29 (1H, s), 7,6 - 7,8 (2H, m), to 7.84 (1H, c), 8,04 - 8,11 (1H, m), 12,11 (1H, c).

Preparative example 112.

A mixture of methyl ester 3-(2-carboxyethyl)-5-(pyrrol-1-yl)benzoic acid (1.5 g), diphenylphosphinite (1,25 g) and triethylamine (0.8 ml) in tert-butyl alcohol (20 ml) is boiled for 7 hours. After cooling to room temperature the reaction mixture is transferred into a water-ethyl acetate. The organic layer is successively washed with 1 N. hydrochloric acid, water and brine and dried over magnesium sulfate. The solvent is evaporated in vacuo and the residue purified column chromatography on silica gel with buerometro ester 3-(2-tert-butoxycarbonylamino)-5-(pyrrol-1-yl)benzoic acid (0,89 g).

So pl. 82 - 83oC.

IR (nujol): 3350, 1725, 1685, 1600 cm-1.

NMR (DMSO-d6) : of 1.32 (9H, c), 2,7 - 2,9 (2H, m), 3,1 - 3,3 (2H, m), 3,88 (3H, s), 6,2 - 6,3 (2H, m), 6,8 - 7 (1H, m), between 7.4 to 7.5 (2H, m), and 7.6 to 7.9 (3H, m).

(+) APCI MACC (m/z): 345 /M+H/+.

Preparative example 113.

A mixture of methyl ester of 3-formyl-5-(pyrrol-1-yl)benzoic acid (1.66 g), 2-aminoethanol (0,88 ml) and molecular sieves 4A (1.7 g) in methanol (40 ml) is stirred for 6 hours at room temperature. Then to the reaction mixture is added sodium borohydride (0.55 g). After stirring 3 hours at room temperature the reaction mixture is transferred into a saturated aqueous solution of sodium bicarbonate and filtered. The filtrate is evaporated in vacuo and the residue purified column chromatography on silica gel with elution with a mixture of chloroform-methanol (20: 1), eluruume fraction containing the target product, collect and evaporation in vacuo get methyl ester 3-(2-hydroxyethylaminomethyl)-5-pyrrol-1-yl)benzoic acid (0.8 g).

So pl. 85 - 87oC.

IR (nujol): 3150, 1715, 1600 cm-1.

NMR (DMSO-d6) : 2,32 (1H, sh.2), 2,58 (2H, t, J = 5.8 Hz), 3,4 - 3,6 (2H, m), 3,80 (2H, s) to 3.89 (3H, s), 4,4 - 4,6 (1H, m), 6,2 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,8 - 8 (3H, m)

(+) APCI MACC (m/Z): 275 /M+H/+.


Methyl ether 3-dimethylaminomethyl-5-(pyrrol-1-yl)-benzoic acid

IR (nujol): 2590, 2565, 2555, 1720, 1600 cm-1.

NMR (DMSO-d6) : are 2.19 (6H, s), 3,51 (2H, s) to 3.89 (3H, s), 6,2 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,7 - 8 (3H, m).

(+) APCI MACC (m/Z): 259 /M+H/+.

Preparative example 115.

To a solution of methyl ester of 3-nitro-5-(pyrrol-1-yl)benzoic acid (35,8 g) in concentrated hydrochloric acid (79 ml) and methanol (79 ml) was added in portions iron (48.6 g). After stirring for 3.5 hours at room temperature the reaction mixture is transferred into a mixture of ethyl acetate with water and filtered. The organic layer is successively washed with water and brine and dried over magnesium sulfate. The solvent is evaporated in vacuum and the grinding of the residue in petroleum ether and diisopropyl ether obtain methyl ester of 3-amino-5-(pyrrol-1-yl)benzoic acid (22.7 g).

So pl. 116 - 117oC.

IR (nujol): 3430, 3330, 1710, 1620, 1600 cm-1.

NMR (DMSO-d6) : of 3.84 (3H, s), the 5.65 (2H, sh.C), 6,2 - 6,3 (2H, m), the 6.9 and 7.3 (5H, m).

(+) APCI MACC (m/Z): 217 /M+H/+.

Preparative example 116.

To a cooled ice mixture methyl ester 3-(2-hydroxyethylaminomethyl)-5-(pyrrol-1-yl)benzoic acid (0.8 g) and tritium the camping transferred into a mixture of ethyl acetate with water. The organic layer was washed with brine and dried over magnesium sulfate. The solvent is evaporated in vacuo and the residue purified column chromatography on silica gel and elution with a mixture of chloroformmethanol (15:1). Eluruume fraction containing the target product, collect and evaporation in vacuo receive the methyl ester of 3-[N-benzyloxycarbonyl-N-(2-hydroxyethyl)aminomethyl] - 5-(pyrrol-1-yl)benzoic acid (1,11 g).

IR (film): 1420, 2950, 1715, 1695, 1600 cm-1.

NMR (DMSO-d6) : 3,3 - 3,6 (4H, m), 3,88 (3H, s), 4,63 (2H, s), 4,79 (1H, t, J = 5,2 Hz), 5,1 - 5,2 (2H, m), 6,3 - 6,4 (2H, m) and 7.1 to 7.2 (7H, m), 7,6 - 7,8 (2H, m), to 7.93 (1H, s).

(+) APCI (MACC (m/Z): 409 /M+H/+.

Preparative example 117.

By the method similar to the method of preparative example 74, received the following connection:

Methyl ester of 2-acetoxy-3-(pyrrol-1-yl)benzoic acid

IR (film): 1765, 1725, 1585 cm-1.

NMR (DMSO-d6) : 2,17 (3H, s), of 3.84 (3H, s), 6,23 - of 6.29 (2H, m), of 6.96 - 7,02 (2H, m), 7,52 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,76 (1H, DD, J = 1.6 Hz, 7.9 Hz), 7,92 (1H, DD, J = 1.6 Hz, 7.9 Hz).

Preparative example 118.

By the method similar to the preparative method of example 75, received the following connection:

Methyl ester 3-(2-formylphenol-1-yl)-2-hydroxybenzoic CI,9 Hz), 7,14 - 7,21 (1H, m), 7,28 - 7,33 (1H, m), to 7.61 (1H, DD, J = 1.7 Hz, 7.9 Hz), 7,88 - of 7.96 (1H, m), 9,43 (1H, s), 10,89 (1H, s).

Preparative example 119.

By the method similar to the method of preparative example 76, received the following connection:

Methyl ester of 2-hydroxy-3-(2-hydroxymethylene-1-yl)-benzoic acid

IR (film): 1670 cm-1.

NMR (DMSO-d6) : of 3.94 (3H, s) to 4.23 (2H, d, J = 5,1 Hz), 4,71 (1H, t, J = 5,1 Hz), 6,06 - 6,16 (2H, m), 6.73 x - 6,79 (1H, m), 7,05 (1H, t, J = 7.9 Hz, 7.9 Hz), to 7.61 (1H, DD, J = 1.7 Hz, 7.9 Hz), 7,88 (1H, DD, J = 1.7 Hz, 7.9 Hz), or 10.9 (1H, C).

Preparative example 120.

By the method similar to the preparative method of example 77, received the following connection:

6-Methoxycarbonyl-4H-pyrrolo/2,1-C//1.4/benzoxazin.

IR (film): 1725 cm-1.

NMR (DMSO-d6) : is 3.82 (3H, s), 5,23 (2H, s), 6,07 - 6,13 (1H, m), 6,28 - 6,36 (1H, m), 7,14 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,42 - 7,66 (2H, m), 7,88 (1H, DD, J = 1.6 Hz, 7.9 Hz).

(+) APCI MACC (m/Z): 230 /M+H/+.

Preparative example 121.

A mixture of methyl ester of 3-aminobenzoic acid (110 g) and 2,5-dimethoxytetrahydrofuran (141,4 ml) in acetic acid (330 ml) is boiled with stirring for 50 minutes, after which the solvent is removed by concentration in vacuo. To the residue is added a mixture of ethyl acetate with bodoglife.com magnesium. Evaporation of the solvent to obtain the residue, which is purified column chromatography on silica gel with elution by chloroform. Eluruume fraction containing the target product, collect and evaporation in vacuo get methyl ester 3-(pyrrol-1-yl)benzoic acid (112,84 g) in the form of butter.

IR (film): 1720, 1590 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 6,3 - 6,38 (2H, s), 7,4 - of 7.48 (2H, m), to 7.59 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,8 - 7,92 (2H, m), with 8.05 (1H, DD, J = 1.9 Hz, 1.9 Hz).

Preparative example 122.

To a solution of methyl ester of 3-(pyrrol-1-yl)benzoic acid (35 g) and dichloromethane (350 ml) was added at a temperature of from -10oC to -20oC dropwise chlorosulfonylisocyanate (18.2 ml) and the mixture is stirred for 1 hour at the same temperature. To the mixture at the same temperature was added dropwise N,N-dimethylformamide (105 ml) and the mixture is stirred for 1 hour at 0o-5oC. Then the reaction mixture is transferred into the water. The separated organic layer was washed with saturated aqueous sodium bicarbonate and water. The organic solution is dried over magnesium sulfate and evaporation in vacuo get methyl ester 3-(2-cyanoprop-1-yl)benzoic acid (30,67 g)

So pl. 89-90oC.

IR (nujol): 2220, 1715, 1590 cm-1.<6 (1H, DD, J = 8 Hz, 8 Hz), a 7.85 - a 7.92 (1H, m), 8,04 and 8.1 (2H, m).

(+) APCI MASS (m/z: 227 (M+H)+.

Elemental analysis for C13H10N2O2< / BR>
Calculated: C 69,02, H 4,46, N 12,38

Found: C 68,69, H 4,46, N OF 12.26

Example 1.

To a solution of guanidine hydrochloride (3.2 g) in dry methanol (40 ml) was added 28% methanol solution of sodium methoxide (6.2 ml) and the mixture is stirred for 30 minutes at room temperature. To the mixture is added methyl ether 3-methylsulphonyl-5-(pyrrol-1-yl)benzoic acid (1.9 g) and the mixture is stirred for 7 hours at the same temperature. The solvent is removed by concentration and the residue is added a mixture of ethyl acetate, tetrahydrofuran and water. The separated organic layer was washed with brine and dried over magnesium sulfate. The residue obtained by evaporation of the solvent, purified column chromatography on alumina with elution with a mixture of chloroform-methanol (19:1, about. /about. ). The fraction containing the target product are collected and evaporated in vacuum. By recrystallization of the residue from a mixture of methanol with diisopropyl ether obtain 2-[3-methylsulphonyl-5-(pyrrol-1-yl)benzoyl]guanidine (0,44 g).

So pl. 235 - 236oC.

IR (nujol): 3500, 3440, 3340, 3240, 1635, 1600, 1320, 1135 cm-1.

YAIR>+
).

Example 2.

By the method similar to the method of example 1, the following compounds:

(1) 2-[{5-(Pyrrol-1-yl)pyridine-3-yl}carbonyl]guanidine

So pl. 147 - 150oC. (decomp).

IR (nujol): 3400, 3300, 1590, 725 cm-1.

NMR (DMSO-d6) : 6,3 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), 8,39 (1H, DD, J = 2.7 Hz, 1.7 Hz), to 8.94 (1H, DD, J = 2.7 Hz), 9,06 (1H, d, J = 1.7 Hz), 6,4 - 7,4 (2H, sh), of 7.6 to 8.4 (2H, sh).

(2) 2-[{5-(3-Methyl-1,2,4-oxadiazol-5-yl)pyridine-3-yl}- carbonyl]guanidine

So pl. 219 - 221oC.

IR (nujol): 3400, 3310, 1660, 1520 cm-1.

NMR (DMSO-d6) : the 2.46 (3H, s), 8,96 (1H, t, J = 2.1 Hz), 9.28 are (1H, d, J = 2.1 Hz), 9,38 (1H, d, J = 2.1 Hz).

MASS (m/z: 247 (M++ 1).

(3) 2-[2-Methoxy-5-methylsulphonyl-3-(pyrrol-1-yl)-benzoyl] guanidine

So pl. 180 - 183oC.

IR (nujol): 3410, 3300, 1675, 1605 cm-1.

NMR (DMSO-d6) : of 3.28 (3H, s), of 3.56 (3H, m), of 6.29 (2H, s), 7,16 (2H, s), compared to 6.6 - 7.4 (2H, sh), 7,81 (1H, d, J = 2.3 Hz), and 7.9 (1H, d, J = 2.3 Hz), 7,5 - 8,3 (2H, sh).

(4) 2-[3-Nitro-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. 211oC.

IR (nujol): 1710, 1530, 1355, 1335, 1260, cm-1.

NMR (DMSO-d6) : 6,36 (2H, m), 7,55 (2H, m), compared to 6.6 - 7.4 (2H, sh), 7,8 - 8,4 (2H, sh), 8,4 - to 8.45 (1H, m), 8,5 - 8,55 (1H, m), 8,65 is 8.7 (1H, m).

MASS (m/z): 274 (M++ 1).

(5) 1715, 1630, 720 cm-1.

NMR (DMSO-d6) : 3,91 (3H, s), 6,32 (2H, m), 7,41 2H, m), 8,08 and 8.1 (1H, m), of 8.37 an 8.4 (1H, m), an 8.5 and 8.6 (1H, m).

MASS (m/z): 287 (M++ 1).

(6) 2-[3-Phenoxybenzoyl]guanidine hydrochloride

So pl. 144 - 145oC.

IR (nujol): 3340, 1700, 1360, 1260, 990, 860 cm-1.

NMR (DMSO-d6) : 7,05 for 7.12 (3H, m), 7,15 - to 7.5 (3H, m), and 7.6 to 7.7 (2H, m), 7.95 is to 8.1 (1H, m), 8,63 (2H sh.C) 8,77 (2H, sh.C), 12,11 (1H, s).

(7) 2-[3-(3-Thienyl)benzoyl]guanidine hydrochloride

T, pl. 224 - 225oC.

IR (nujol): 3350, 1690, 1280, 745, 720 cm-1.

NMR (DMSO-d6) : 7,6 - 7,8 (3H, m), of 7.96 to 8.2 (3H, m), to 8.57 (2H, s), to 8.62 (1H, s), 8,88 (2H, s), to 12.28 (1H, s).

MASS (m/z): 246 (M++ 1).

(8) 2-[3-Pyrazole-1-yl)benzoyl]guanidine

So pl. 155 - 157oC.

IR (nujol): 3430, 3330, 3200, 3100, 1670 cm-1.

NMR (DMSO-d6) : 6,13 - 8,7 (4H, sh), 6,55 (1H, DD, J = 1,8 Hz, 2.4 Hz), 7,51 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,76 (1H, d, J = 1.4 Hz), 7,83 - of 7.95 (1H, m), to 7.99 (1H, d, J = 7.9 Hz), 8,49 (1H, d, J = 2.4 Hz), 8,54 (1H<d, J = 1,8 Hz).

(9) 2-[3-(Pyrrol-1-yl)benzoyl]guanidine

So pl. 172 - 173oC.

IR (nujol): 3310, 3120, 1665, 1635, 1600 cm-1.

NMR (DMSO-d6) : 6,13 and 8.6 (4H, sh), 6,22 to 6.35 (2H, m), 7,28 - 7,39 (2H, m), 7,47 (1H, d, J = 7.8 Hz, 7.8 Hz), to 7.64 (1H, d, J = 7.8 Hz), 7,94 (1H, d, J = 7.8 Hz), 8,17 (1H, s).

MASS (m/z): 2 ideno: C 62,95, H OF 5.29, N 24,59

(10) 2-[3-(1H-tetrazol-1-yl)benzoyl]guanidine

So pl. 227 - 230oC.

IR (nujol): 3410, 3325, 3280, 3220, 3125, 1655, 1600 cm-1.

NMR (DMSO-d6) : 6,37 and 8.6 (4H, sh), to 7.68 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,98 (1H, d, J = 7.9 Hz), 8,23 (1H, d, J = 7.9 Hz), 8,55 (1H, DD, J = 1.7 Hz, 1.7 Hz), 10,16 (1H, s).

(11) 2-[3-(Pyrrol-1-yl)benzoyl]guanidine

So pl. 172 - 173oC.

IR (nujol): 3310, 3120, 1665, 1635, 1600 cm-1.

NMR (DMSO-d6) : 6,13 and 8.6 (4H, sh), 6,22 to 6.35 (2H, m), 7,28 - 7,39 (2H, m), 7,47 (1H, DD, J = 7.8 Hz, 7.8 Hz), and 7.4 (1H, d J = 7.8 Hz), 7,94 (1H, d, J = 7.8 Hz), 8,17 (1H, s).

(12) 2-[5-(Pyrazole-3-yl)pyridine-3-yl-carbonyl]guanidine

So pl. 264 - 265oC.

IR (nujol): 3440, 3310, 3170, 3100, 1690 cm-1.

NMR (DMSO-d6) : 6,37 an 8.4 (4H, sh), 6,85 (1H, d, J = 2.3 Hz), to 7.84 (1H, d, J = 2.3 Hz), a total of 8.74 (1H, DD, J = 2 Hz, 2 Hz), 9,06 (1H, d, J = 2 Hz), 9,11 (1H, d, J = 2 Hz), 13,11 (1H, sh.C).

MASS (m/z): 231 (M++ 1).

Elemental analysis for C10H10N6O

Calculated: C 52,17, H of 4.38, N 36,50

Found: C 52,22, H 4,50, N 36,31

(13) 2-[3,5-Di(pyrrol-1-yl)benzoyl]guanidine

So pl. 220 - 221oC.

IR (nujol): 3480, 3430, 3300, 3200, 1630, 1600 cm-1.

NMR (DMSO-d6) : 6,28 - 6,39 (4H, m), 6,5 - 8,4 (4H, sh), 7,45 - 7,53 (4H, m), 7,82 (1H, DD, J = 2.1 Hz and 2.1 Hz), 8,03 (2H, d, J = 2.1 Hz).

MASS (m/z): 294 Found: C 65,79, H 5,22, N 23,60

(14) 2-[3-(2,5-Dimethylpyrrole-1-yl)benzoyl]guanidine

So pl. 204 - 205oC.

IR (nujol): 3430, 3350, 3300, 1650, 1600 cm-1.

NMR (DMSO-d6) : 1,95 (6H, s), and 5.8 (2H, s), 6 and 8.3 (4H, sh), 7,32 - 7,39 (1H, m), 7,53 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,92 (1H, DD. J = 1.7 Hz, 1.7 Hz), 8,06 - to 8.12 (1H, m).

MASS (m/z): 257 (M + 1).

Elemental analysis for C14H16N4O

Calculated: C 65,61, H 6,29, N 21,86

Found: C 65,77, H is 6.54, N 21,70

(15) 2-[2-(Pyrrol-1-yl)benzoyl]guanidine

So pl. 172 - 173oC.

IR (nujol): 3380, 1655, 1595 cm-1.

NMR (DMSO-d6) : 6,1 - 6,18 (2H, m), 6,35 to 8.2 (4H, sh), 6,94 - 7,03 (2H, m), 7,25 (1H, DD, J = 1.6 Hz and 7.1 Hz), 7,3 - of 7.48 (3H, m).

MASS (m/z: 229 (M++ 1).

(16) 2-[3-Methylsulphonyl-4-piperidino-5-(pyrrol-1-yl)- benzoyl]guanidine

So pl. 178 - 179oC.

IR (nujol): 3425, 3350, 3170, 1650, 1590, 1140 cm-1.

NMR (DMSO-d6) : 0,8 - 1,8 (6H, m), 2,1 - 2,48 (2H, m), 2.95 and of 3.28 (2H, m), 3,4 (3H, s), 6.22 per 6,32 (2H, m), from 6.4 to 8.4 (4H, sh), 6,29 - 7,02 (2H, m) to 8.14 (1H, d, J = 2 Hz), and 8.7 (1H, d, J = 2 Hz).

MASS (m/z): 389 (M+).

Example 3.

To a solution of guanidine hydrochloride (2.7 g) in methanol (12 ml) is added sodium methoxide (5,13 g, 28% in methanol) and the mixture is stirred for 15 minutes in nitrogen atmosphere. To the resulting mixture p is the transition mixture is transferred into a mixture of ethyl acetate (100 ml) with water (50 ml). The organic layer is successively washed with 5 N. aqueous sodium hydroxide solution and brine, dried over magnesium sulfate and evaporated in vacuum. The residue is purified column chromatography on aluminium oxide (100 ml) with elution with a mixture of chloroform-methanol (10:1). Containing the target product fractions are collected and evaporated in vacuum. The residue is crystallized 4 n solution of hydrogen chloride in ethyl acetate. By recrystallization of the crystalline product from ethanol 2-[3-phenylbenzyl]guanidine hydrochloride (274 mg).

So pl. 168 - 169oC.

IR (nujol): 3325, 1700, 1630, 1260, 740 cm-1.

NMR (DMSO-d6) : 7,4 - 7,6 (3H, m), and 7.7 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,8 - 7,9 (2H, m), 8 - 8,01 (2H, m), 8,4 - to 8.45 (1H, m), 8,58 (2H, sh), 8,82 (2H, sh), 12,25 (1H, s).

MASS (m/z): 240 (M++ 1).

Example 4.

By the method similar to the method of example 3, obtained the following link:

4,4-Dimethyl-5-diaminopyrimidine-8-methylsulphonyl - 4H-pyrrolo/2,1-c//1,4/benzoxazine hydrochloride

So pl. 165 - 166oC.

IR (nujol): 3370, 3280, 3200, 1695, 1320, 1130 cm-1.

NMR (DMSO-d6) : of 1.64 (6H, s), of 3.57 (3H, s), from 6.22 (1H, DD, J = 1.3 Hz, 3.2 Hz), 6,38 (1H, DD, J = 3.2 Hz, 3.2 Hz), 7,74 (2H, DD, J = 1.3 Hz, 3.2 Hz), 7,98 (1H, d, J = 2.1 Hz), 8,39 (1H, d, J = 2.1 Hz), 8,45 - Heidenau ice to a solution of 6-carboxy-8-chloro-4,4-dimethyl - 4H-pyrrolo/2,1-c//1,4/benzoxazine (0.7 g) and triethylamine (0,39 ml) in tetrahydrofuran (7 ml) and pyridine (14 ml) add isobutylparaben (0,38 g). After stirring 2 hours at 7 to 10oC to the reaction mixture are added guanidine (0.3 g) and all is stirred for 8 hours at room temperature. Then the reaction mixture is transferred into a mixture of ethyl acetate (100 ml) with water (100 ml). The organic layer is successively washed with 10% aqueous potassium carbonate solution, brine, dried over magnesium sulfate and evaporated in vacuum. Treatment of the residue with ethanolic hydrogen chloride poluchaut hydrochloride 8-chloro-4,4-dimethyl-6-diaminomethylene - 4H-pyrrolo/2,1-c//1,4/benzoxazine.

So pl. 150oC.

IR (nujol): 3350, 1690, 730 cm-1.

NMR (DMSO-d6in ) 1.6 (6H, s), 6,17 (1H, DD, J = 3,4 Hz, 1.3 Hz), 6,33 (1H, DD, J = 3,4 Hz and 3.4 Hz), 7,51 (1H, d, J = 2.4 Hz), 7,63 (1H, DD, J = 3,4 Hz, 1.3 Hz), 8,11 (1H, d, J = 2.4 Hz), 8.4 to 8.9 in (4H, m), 11,77 (1H, s).

Example 6.

To a mixture of 2-or 3 - (1H-tetrazol-1-yl)benzoyl guanidine (1.4 g) and methanol (30 ml) is added 4 n solution of hydrogen chloride in dioxane (3 ml) and the mixture is stirred for 1 hour at room temperature. To the mixture is added diisopropyl ether (30 ml) and the precipitate filtered off. By recrystallization of the precipitate from methanol receive hydrochloride 2-[3-(1H-tetrazol-1-yl)benzoyl]guanidine (1,05 g).

So pl. 250 - 251oC.

IR (nujol): 3390, 3230, 3080,), 10,28 (1H, s), 12,36 (1H, s).

MASS (m/z): 232 (M++ 1 of free base).

Example 7.

By the method similar to the method of example 6, the following compounds:

(1) 2-[3-(Pyrazole-1-yl)benzoyl]guanidine hydrochloride

So pl. 252 - 253oC.

IR (nujol): 3360, 3270, 1700, 1620, 1585 cm-1.

NMR (DMSO-d6) : 6,57 is 6.67 (1H, m), 7,73 (1H, DD, J = 8 Hz, 8 Hz), 7,83 (1H, d, J = 1.6 Hz), 8 and 8.1 (1H, m), 8.17 and compared to 8.26 (1H, m), 8,55 - 8,73 (3H, m), 8,73 - 8,9 (3H, m), to 12.28 (1H, s).

MASS (m/z): 230 (M1+ 1) of free base).

(2) 2-[3-(Pyrrol-1-yl)benzoyl]guanidine hydrochloride

So pl. 215 - 216oC.

IR (nujol): 3350, 3100, 1700, 1690, 1625 cm-1.

NMR (DMSO-d6) : 6,28 - 6,38 (2H, m), and 7.6 to 7.75 (3H, m), 7,9 - 8,63 (2H, m), to 8.45 (1H, s), 8,61 (2H, s), 8,88 (2H, s), 12,43 (1H, s).

Elemental analysis for C12H12N4O HCl

Calculated: C 54,45, H 4,95, N 21,17, Cl 13,39

Found: C 54,52, H 5,04 N 21,11, Cl 13,22

Example 8.

To a solution of guanidine hydrochloride (62,1 g) in N,N-dimethylformamide (150 ml) under nitrogen atmosphere add 28% solution of sodium methoxide in methanol (106 ml). After stirring for 30 minutes at room temperature to the reaction mixture add a solution of methyl ester of 3-hydroxymethyl-5-(pyrrol-1-yl)benzoic to the ü carry with stirring into water (1.5 l). The formed precipitate is filtered off, washed with water and purified column chromatography on silica gel with elution with a mixture of chloroform-methanol (10:1). Eluruume fraction containing the target product are collected and evaporated in vacuum.

The residue is dissolved in ethanol (70 ml) and crystallized from a small excess of 4 n solution of hydrogen chloride in ethyl acetate. By recrystallization of the crystalline product from aqueous ethanol hydrochloride 2-[3-hydroxymethyl-5-(pyrrol-1-yl)benzoyl]guanidine (7,3 g).

So pl. 198 - 199oC.

IR (Nucl): 3350, 3100, 1720 cm-1.

NMR (DMSO-d6) : with 4.64 (2H, s), 6,3 - 6,4 (2H, m), and 7.6 to 7.7 (2H, m), 7,86 (2H, m), a 8.34 (1H, m), 8,59 (2H, sh.C) 8,84 (2H, sh.C), 12,32 (1H, s)

MASS (m/z): 259 (M++ 1).

Example 9.

By the method similar to the methods of examples 1, 3 and 8, the following compounds:

(1) 2-[3-(2-Were)benzoyl]guanidine hydrochloride

So pl. 187 - 189oC.

IR (nujol): 1680, 1560, 1230, 740 cm-1.

NMR (DMSO-d6) : of 2.26 (3H, s), 7,28 - 7,34 (4H, m), 7,63 - 7,74 (2H, m), 8,07 (1H, s) to 8.14 (1H, DDD, J = 6,7 Hz and 2.1 Hz, 2.1 Hz), 8,58 (2H, sh.C) is 8.75 (2H, sh.C) 12,04 (1H, m).

MASS (m/z): 254 (M++ 1).

(2) 2-[3-(2,5-Dichloroprop-1-yl)benzoyl]guanidine

So pl. 201 - 204) was 7.45 (1H, d, J = 7,7 Hz), and 7.6 (1H, DD, J = 7,7 Hz), to 7.99 (1H, s), 8,18 (1H, d, J = 7,7 Hz).

(3) 2-[3-(2-Acetylpyrrole-1-yl)benzoyl]guanidine

IR (nujol): 3100 - 3300, 1600 - 1660 cm-1.

NMR (DMSO-d6) : to 2.41 (3H, s), 6.3 to 8.3 (4H, sh), 6,65 and 6.7 (1H, m), 7,38 was 7.45 (1H, m), 7,53 (1H, DD, J = 7.8 Hz, 7.8 Hz), of 7.75 (1H, d, J = 7.8 Hz), of 8.04 (1H, d, J = 7.8 Hz), 8,15 - 8,18 (1H, m), 8,21 - 8,24 (1H, m).

(4) 2-[4-n-Butyl-3-(pyrrol-1-yl)benzoyl]guanidine

So pl. 163 - 165oC.

IR (nujol): 3400, 3170, 1635, 1590 cm-1.

NMR (DMSO-d6) : of 0.77 (3H, t, J = 7,1 Hz), of 1.05 to 1.45 (4H, m), 2,42 of $ 2.53 (2H, m), 6,1 - a 8.4 (4H, sh), to 6.19 and 6.25 (2H, m), 6,95 - 6,9 (2H, m), 7,38 (1H, d, J = 7.9 Hz), 7,92 - 8,03 (2H, m).

(5) 2-[4-Methyl-3-(pyrrol-1-yl)benzoyl]guanidine

So pl. 182 - 185oC.

IR (nujol): 3400, 3170, 1635, 1590 cm-1.

NMR (DMSO-d6) : are 2.19 (3H, s), 6,1 - a 8.4 (4H, sh), 6,2 and 6.25 (2H, m), 6,9 - to 6.95 (2H, m), 7,37 (1H, d, J = 8,3 Hz), to $ 7.91 - 8 (2H, m).

(6) 2-[3-(2-Carbamoylphenoxy-1-yl)benzoyl]guanidine

So pl. 155 - 156oC.

IR (nujol): 3450, 3360, 1655, 1600 cm-1.

NMR (DMSO-d6) : 6,21 (1H, DD. J = 2,8 Hz and 3.7 Hz), 6,38 - 8,2 (6H, sh), 6,9 (1H, DD. J = 1.7 Hz, 3,7 Hz), 7 - 7,05 (1H, m), 7,27 and 7.36 (1H, m), the 7.43 (1H, DD, J = 1.6 Hz and 7.6 Hz), to $ 7.91 - of 7.95 (1H, m), 7,95 - 8,03 (1H, m).

(7) 2-[-[(Z)-2-Gidroksiiminobetulonovoi-1-yl]benzoyl]guanidine

So pl. 131 - 132oC.

IR (nugo is H, m), 7,46 - to 7.64 (2H, m), 8 to 8.2 (2H, m), of 11.45 (1H, s).

(8) 2-[3-(E)-2-gidroksiiminobetulonovoi-1-yl]benzoyl]guanidine

So pl. 158 - 159oC.

IR (nujol): 3440, 3300, 3130, 1660, 1600 cm-1.

NMR (DMSO-d6): 6,15 an 8.4 (4H, m), 6,26 - 6,32 (1H, m), 6,6 - only 6.64 (1H, m), 7,08 - 7,11 (1H, m), 7,44 (1H, d, J = 7.8 Hz), 7,53 (1H, DD, J = 7.8 Hz, 7.8 Hz), to 7.77 (1H, s), 8,01 (1H, s), of 8.09 (1H, d, J = 7.8 Hz), 10,84 (1H, s).

(9) 2-[3-(2-Dimethylaminomethylene-1-yl)benzoyl]guanidine

So pl. 91 - 94oC.

IR (nujol): 3370, 3200, 1650, 1595 cm-1.

NMR (DMSO-d6) : of 2.08 (6H, s), up 3.22 (2H, s), 6,12 - 6,18 (1H, m), 6,3 - 8,4 (4H, sh. ), 7,47 (1H, d, J = 7.8 Hz, 7.8 Hz), the 7.65 (1H, d, J = 7.8 Hz), 8,03 (1H, d, J = 7.8 Hz), 8,15 (1H, s).

(10) 2-[3-(2-Cyanoprop-1-yl)benzoyl]guanidine

So pl. 136 - 138oC.

IR (nujol): 3390, 2220, 1637 cm-1.

NMR (DMSO-d6) : 6,3 an 8.4 (4H, sh), 6,46 (1H, DD, J = 2,8 Hz, 3.9 Hz), 7,24 (1H, DD, J = 1.6 Hz, 3.9 Hz), 7,56 (1H, DD, J = 1.6 Hz, 2.8 Hz), 7,58 - of 7.69 (2H, m), 8,11 - 8,19 (2H, m).

(11) 2-[4-n-Butyl-3-(2-cyanoprop-1-yl)benzoyl]guanidine

IR (film): 3350, 2230, 1660 - 1590 (sh.) cm-1.

NMR (DMSO-d6) : 0,76 (3H, t, J = 7.2 Hz), 1,05 of 1.46 (4H, m), 2,3 - by 2.55 (2H, m), a 6.2 to 8.7 (4H, sh), 6,44 (1H, DD, J = 2.7 Hz, 3.9 Hz), 7,15 - 7,22 (1H, DD, J = 1.5 Hz, 3.9 Hz), of 7.36 - 7,41 (1H, DD, J = 1.5 Hz, 2.7 Hz), and 7.5 (1H, d, J = 8 Hz), 8,01 (1H, d, J = 1.5 Hz), 8,13 (1H, DD, J = 1.5 Hz, 8 Hz).

(12) 2-[3-[(4�Jol): 3400, 1630, 1610 cm-1.

NMR (DMSO-d6) : 1,2 - 2 (4H, m), 3 to 4.2 (5H, m), 4,82 (1H, d, J = 3,4 Hz), 6,2 - 6,4 (2H, m), 7,3 - 7,5 (2H, m), and 7.6 to 7.7 (1H, m), 7,8 - 7,9 (1H, m), of 8.1 to 8.2 (1H, m).

MASS (m/z): 356 (M++ 1).

(13) 2-[3-carboxy-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. > 250oC.

IR (nujol): 3370, 1680, 1580 cm-1.

NMR (DMSO-d6) : 6,2 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), of 8.1 to 8.2 (1H, m), 8,3 an 8.4 (1H, m), 8,8 - 8,9 (1H, m).

MASS (m/z): 273 (M++ 1).

(14) 2-[3-[(4-Methylpiperazin-1-yl)carbonyl] -5-(pyrrol-1-yl) benzoyl] guanidine hydrochloride

So pl. 220 - 221oC.

IR (nujol): 3300, 1700, 1640, 1600 cm-1.

NMR (DMSO-d6) : 2,78 (3H, s), 3 to 3.8 (8H, m), 6,3 - 6,4 (2H, m), 7,7 - 7,8 (2H, m), of 7.9 to 8.1 (2H, m), an 8.5 and 8.6 (1H, m), and 8.7 (2H, sh.C) 8,91 (2H, sh.C).

MASS (m/z): 355 (M++ 1).

(15) 2-[3-Methoxymethyl-5-(pyrrol-1-yl)benzoyl]guanidine hydrochloride

So pl. 193 - 194oC.

IR (nujol): 3340 - 3100, 1690, 1620, 1600 cm-1.

NMR (DMSO-d6) : to 3.36 (3H, s) 4,55 (2H, s), 6,3 - 6,4 (2H, m), and 7.6 to 7.7 (2H, m), 7,8 - 7,9 (2H, m), 8,3 an 8.4 (1H, m), 8,61 (2H, sh.C), 8,65 (2H, sh.C), KZT 12.39 (1H, s).

MASS (m/z): 273 (M++ 1).

(16) 2-[5-(2-Cyanoprop-1-yl)-3-hydroxymethylbenzene] guanidine hydrochloride

So pl. 246 - 247oC.

IR (nujol): 3150, 2220, 1710 cm-1 (4H, W.C) to 12.28 (1H, s).

MACC (m/z): 284 (M++1).

(17) 2-[3-[(2-Dimethylaminoethyl)carbarnoyl] -5-(pyrrol-1-yl) benzoyl]guanidine

So pl. 140-145oC.

IR (nujol): 3400, 1640, 1580 cm-1.

NMR (DMSO-d6) : of 2.25 (6H, s), 2,4-2,6 (2H, m), 3,3-3,5 (2H, m), 6,3-6,4 (2H, m), between 7.4 to 7.5 (2H, m), 8-1,1 (1H, m), and 8.2 and 8.3 (1H, m), 8,4 -8,5 (1H, m) 8,64 (1H, t, J=5.6 Hz).

MACC (m/z): 343 (M++1).

(18) 2-[3-(2-Cyano-5-dimethylaminomethylene-1-yl)benzoyl] - guanidine hydrochloride

So pl. 135-138oC.

IR (nujol): 3300, 2230, 1700 cm-1.

NMR (DMSO-d6) : to 2.57 (6H, s), 4,28 (2H, s), to 6.95 (1H, d, J=4 Hz), 7,32 (1H, d, J=4 Hz), 7,86 91H, DD, J=7.9 Hz), of 7.96 (1H, d, J=7.9 Hz), 8.34 per-8,42 (2H, m), and 8.7 (2H, s), cent to 8.85 (2H, s), 10,94 (1H, s), to 12.52 (1H, s).

MACC (m/z) : 311 (M++1 of free base).

(19) 2-[3-(2-Methylpyrrole-1-yl)benzoyl]guanidine hydrochloride

So pl. 213-214oC.

IR (nujol) : 3350, 1700 cm-1.

NMR (DMSO-d6) : of 2.23 (3H, s), 6-6,04 (1H, m), a 6.1-6,16 (1H, m), 7-7,05 (1H, m), 7.68 per-7,8 (2H, m), 8,03-8,11 (2H, m), 8,56 (2H, s), 8,67 (2H, s), 12,07 (1H, s).

MACC (m/z: 243 (M++1 of free base).

(20) 2-[3-(4-Cyanophenyl)benzoyl]guanidine hydrochloride

So pl. 243-245oC.

IR (nujol): 3350, 2230, 1710 cm-1.

NMR (DMSO-d6) : of 7.75 (1H, DD, J=7,7 Hz, 7.7 Hz), 7,98 the l]guanidine hydrochloride

So pl. 236-238oC.

IR (nujol): 3200, 1710, 1560, 1300, 1230, 1140, 960, 760 cm-1.

NMR (DMCO-d6) : of 2.93 (3H, s) of 7.48 (1H, DD, J=7,2 Hz, 1.6 Hz), 7,62-a 7.85 (4h, m), 8,1-to 8.14 (2H, m), 8,23 (1H, d, J=7,7 Hz), 8,59 (2H, sh.C.), 8,77 (2H, sh.C.), 12,17 (1H, s).

MASS (m/z): 318 (M++1).

(22) 2-[3-(2-Triptoreline)benzoyl]guanidine hydrochloride

So pl. 141-143oC.

IR (nujol): 3300, 1700, 1230, 1110, 740 cm-1.

NMR (DMSO-d6) : 7,51 (1H, d, J=7.5 Hz), 7,62-of 7.82 (4H, m), 7,88 (1H, d, J=7,6 Hz), 8,02 (1H, s), 8,2-of 8.25 (1H, m), to 8.57 (2H, sh.C.), 8,67 (2H, sh.C.), 11,99 (1H, s).

MASS (m/z): 308 (M++1).

(23) 2-[3-(2-Methoxyphenyl)benzoyl]guanidine hydrochloride

So pl. 182-183oC.

IR (nujol): 3340, 1700, 1250, 1020, 730 cm-1.

NMR (DMSO-d6) : with 3.79 (3H, s), 7.03 is-7,17 (2H, m), of 7.36-7,47 (2H, m), a 7.62 (1H, DD, J=7.9 Hz, 7.9 Hz), to 7.84 (1H, d, J=7.9 Hz), 8,11 (1H, d, J=7.9 Hz), 8,18 (1H, s), 8,61 (2H, sh.C) 8,79 (2H, sh.C.). to 12.1 (1H, s).

MASS (m/z): 270 (M++1).

(24) 2-[3-(-Naphthyl)benzoyl]guanidine hydrochloride

So pl. 132-134oC.

IR (nujol): 1700, 1560, 1250, 750 cm-1.

NMR (DMSO-d6) : 7,55-to 7.59 (2H, m), of 7.75 (1H, DD, J=7.8 Hz, 7.8 Hz), of 7.96 were 8.22 (6H, m), 8,49 (1H, s), 8,55 (2H, sh.C) 8,61 (1H, s), 8,78 (1H, sh. C), and 12.2 (1H, s).

MASS (m/z): 290 (M++1).

(25) 2-[3-(1-Naphthyl)benzoyl]guanidine hydrochlo 7,52-7,88 (7H, m), 8-8,07 (2H, m), and 8.2 to 8.3 (2H, m), 8,66 (2H, sh.C) 8,79 (2H, sh.C), 12,17 (1H, s).

MASS (m/z): 290 (M++1).

(26) 2-[3-(3-Methoxyphenyl)benzoyl]guanidine hydrochloride

So pl. 166-167oC.

IR (nujol): 3250, 1700, 1250, 1030, 730 cm-1.

NMR (DMSO-d6) : a 3.87 (3H, s), of 6.96? 7.04 baby mortality (1H, m), 7,35-7,42 (3H, m), 7,68 (1H, DD, J=7.8 Hz), 7.8 Hz), 8,01-8,1 (2H, m), and 8.5 (1H, s), to 8.62 (2H, sh.C.), 8,89 (2H, sh.C.), 12,38 (1H, s).

MASS (m/z): 270 (M++1).

(27) 2-[3-(2-Morpholinoethyl)-5-(pyrrol-1-yl) benzoyl]guanidine the dihydrochloride

So pl. 195-198oC.

IR (nujol): 1695, 1250, 720 cm-1.

NMR (DMSO-d6) : 3-4,1 (10H, m), 6,3-6,36 (2H, m), 7,79-7,81 (2H, m), 8,35 (1H, s), 8,53 (1H, s), 8,63 (1H, s). of 8.8 (2H, s). 9,34 (1H, m), 10,85 (1H, sh.C), 12,47 (1H, s).

MASS (m/z): 385 (M+1).

(28) 2-[3-(Thiophene-2-yl)benzoyl]guanidine hydrochloride

So pl. 225-226oC.

IR (nujol): 3360, 1700, 1280, 725 cm-1.

NMR (DMSO-d6) : 7,15-of 7.25 (1H, m), and 7.6 to 7.7 (2H, m), 7,8-a 7.85 (1H, m), 7.95 is-with 8.05 (2H, m), 8,48 and 8.5 (1H, m), 8,59 (2H, sh), 8,81 (2H, sh), 12,21 (1H, s).

MASS (m/z): 246 (M+1).

(29) 2-[3-(Thiazol-2-yl)benzoyl]guanidine the dihydrochloride

So pl. 236-239oC (decomp).

IR (nujol): 3375, 1700, 1455, 750 cm-1.

NMR (DMSO-d6) : to 7.84 (1H, t, J=7.8 Hz, 7.8 Hz), to $ 7.91 (1H, d, J=3.2 Hz), 8,01 (1 H, d, J=3.2 Hz), 8,25-8,32 (2H, m), 8.6 out of nidina hydrochloride

So pl. 244-245oC.

IR (nujol): 1690, 1580, 720 cm-1.

NMR (DMSO-d6) : 6,3-6,34 (2H, m), 7.68 per-7,73 (2H, m), 7,87 (1H, DD, J= 1.5 Hz, 1.5 Hz), 8,11 (1H, DD, J=1.5 Hz, 1.5 Hz), and 8.4 (1H, DD, J=1.5 Hz, 1.5 Hz), 8,58 (2H, sh.C) 8,77 (2H, sh.C) 12,42 (1H, sh.C).

MASS (m/z): 263 (M+1).

(31) 2-[3-Acetyl-5-(pyrrol-1-yl)benzoyl]guanidine hydrochloride

So pl. 292-293oC.

IR (guidal): 1690, 1240, 1080, 870 cm-1.

NMR (DMSO-d6) : 2,75 (3H, s), 6,3-6,4 (2H, m), 7,7-7,8 (2H, m). a 8.34 (1H, s), and 8.4 (1H, s), to 8.62 (2H, sh.C.), 8,83 (2H, sh.C.), 12,55 (1H, s).

MASS (m/z) : 271 (M+1).

(32) 2-[3-(4-Methoxyphenyl)benzoyl]guanidine hydrochloride

So pl. 242-243oC.

IR (nujol): 1690, 1295, 830 cm-1.

NMR (DMSO-d6) : 3,81 (3H, s), 7,06 (2H, d, J=8,8 Hz), the 7.65 (1H, DD, J= 7.9 Hz), 7,81 (2H, d, J=8,8 Hz), 7.95 is-with 8.05 (2H, m), to 8.41 (1H, DD, J=1.7 Hz), 8,56 (2H, sh.C.), 8,81 (2H, sh.C.), 12.2 (1H, s).

MASS (m/z): 270 (M+1).

(33) 2-[3-(3-Morpholinopropan)-5-pyrrol-1-yl)- benzoyl]the guanidine dihydrochloride

So pl. 195-197oC. (decomp.).

IR (nujol): 1700, 1650, 1240 cm-1.

NMR (DMSO-d6) : 1,9-2,2 (2H, m), 2,9-3,3 (4H, m), 3,3-3,55 (4H, m), 3.7 to 4.1 (4H, m), 6,3-6,4 (2H, m), 7,7-7,8 (2H, m), of 8.37 (1H, s), to 8.41 (1H, s), 8,61 (1H, c), 8,72 (2H, s), cent to 8.85 (1H, s), 9,16 (1H, t, J = 5.6 Hz), 10,96 (1H, sh.C.), 12,55 (1H, s).

MACC (m/z): 399 (M+1).

(34) 2-[2-Naphtol]g>) : 7,6-7,8 (2H, m), 8-8,2 (4H, m), 8,67 (2H, s), 8,88 (2H, s), 8,96 (1H, s), of 12.33 (1H, s).

MACC (m/z: 214 (M+1).

(35) 2-[3-(2-Cyanophenyl)benzoyl]guanidine hydrochloride

So pl. 204-205oC.

IR (nujol): 2225, 1690, 720 cm-1.

NMR (DMSO-d6) : of 7.6 to 7.9 (4H, m), 8 (1H, DD, J = 7.2 Hz, 7.2 Hz), 8,2-8,35 (2H, m), and 8.6 (2H, sh.C.), 8,77 (2H, sh.C.), 12,25 (1H, s).

MACC (m/z): 265 (M+1).

(35) 4,4-Dimethyl-8-(diaminotrinitrobenzene)-4H-pyrrolo /2,1-C//1,4/benzoxazine hydrochloride

So pl. 276-277oC.

IR (nujol): 3480, 3180, 1692, 1630 cm-1.

NMR (DMSO-d6) : 1,6 (6H, s), x 6.15 (1H, DD, J = 1.4 Hz, 3.2 Hz), 6,33 (1H, DD, J = 3.2 Hz, 3.2 Hz), 7.23 percent (1H, d, J = 8.6 Hz), to 7.77 (1H, DD, J = 1.4 Hz, 3.2 Hz), 7,83 (1H, DD, J = 2.1 Hz), 8.6 Hz), of 8.47 (2H, s) 8,71 (1H, d, J = 2.1 Hz), 8,79 (2H, s), 12,13 (1H, m).

MACC (m/z): 285 (M++1 of free base).

Example 10.

To a mixture of guanidine hydrochloride (1.6 g) and 28% methanolic solution of sodium methoxide (3 ml) in N,N-dimethylformamide (8 ml) was added methyl ether 3-(2-cyano-5-methylpyrrole-1-yl)benzoic acid (0.8 g) and the mixture is stirred for 4 hours at room temperature. The mixture is then transferred into water-ethyl acetate. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuum. The residue is dissolved in methanol (1 diisopropyl ether. The formed precipitate is filtered off and recrystallization from methanol-water get 2-[3-(2-cyano-5-methylpyrrole-1-yl)benzoyl]guanidine methanesulfonate (0,98 g).

So pl. 233-234oC.

IR (nujol): 3300, 2220, 1165, 1045 cm-1.

NMR (DMSO-d6) : of 2.15 (3H, s), of 2.34 (3H, s), of 6.26 (1H, d, J = 3,9 Hz), 7,14 (1H, d, J = 3,9 Hz), 7,83-7,89 (2H, m), of 7.96-to 7.99 (1H, M), 8.07-a to 8.14 (1H, m), 8,14-8,6 (4H, sh.C.), 11,34 (1H, s).

MACC (m/z): 268 (M++1 of free base).

Example 11.

By the method similar to the method of example 10, the following connection:

2-[3-Hydroxymethyl-5-pyrrol-1-yl)benzoyl]guanidine methanesulfonate

So pl. 171-172oC.

IR (nujol): 3330, 3120, 1690, 1600 cm-1.

NMR (DMSO-d6) : to 2.42 (3H, s), of 4.66 (2H, s), 6,3-6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,7-8 (3H, m), 8,43 (4H, sh.C.), 11,41 (1H, s).

MAC (m/z): 259 (M++1).

Example 12.

To guanidine hydrochloride (4.7 g) in dry N,N-dimethylformamide (14 ml) was added a 28% solution of sodium methoxide in methanol (8.6 ml) and the mixture is stirred for 20 minutes at room temperature. Then added to the mixture dimethyl 5-(2-cyanoprop-1-yl)isophthalic acid (1.4 g) and the mixture is stirred for 4 hours at the same temperature. Then the reaction mixture under stirring p is(2-cyanoprop-1-yl)-5- (diaminotrinitrobenzene)benzoyl]guanidine (0.88 g).

So pl. 251-253oC

IR (nujol): 3340 (W.), 2220, 1690, 1640 cm-1.

NMR (DMSO-d6) : 6,03-8,7 (8H, s), 6.42 per-of 6.49 (1H, m), 7,2-7,26 (1H, m), 7,54-to 7.59 (1H, m), by 8.22 (2H, s), cent to 8.85 (1H, s).

Example 13.

By the method similar to the method of example 12, the following connection:

2-[3-(Diaminomethylene)-5-(pyrrol-1-yl)-benzoyl] - guanidine hydrochloride

So pl. 257oC.

IR (nujol): 1700, 1575, 1070 cm-1.

NMR (DMSO-d6) : 6,34-6,37 (2H, m), 7,8-to 7.93 (2H, m), of 8.37 (1H, s), 8,66 (2H, sh.C.), 8,79 (4H, sh.C.), to 12.58 (1H, s).

Example 14.

To a mixture of 5-cyano-3-(pyrrol-1-yl)benzoic acid (2 g), guanidine hydrochloride (2.7 g) and triethylamine (7.2 ml) in N,N-dimethylformamide (30 ml) is added 2-chloro-1-methyl-pyridiniumyl (3.6 g) and the mixture is stirred for 4 hours at room temperature. Then the reaction mixture is transferred to a mixture of ethyl acetate-tetrahydrofuran-water and adding potassium carbonate establish a pH of 10. Separate the organic layer washed with brine and dried over magnesium sulfate. The solvent is removed by concentration and presidenial of the residue from ether to obtain 2 - 5-cyano-3-(pyrrol-1-yl)benzoyl guanidine (1,49 g).

So pl. 198-200oC.

IR (nujol): 3480, 3400, 3300, 2230, 1620, 1600 cm-1.

Yak, similar to the method of example 14, the following compounds:

(1) 2-[3-(2-Cyanoprop-1-yl)benzoyl]guanidine

So pl. 136-138oC.

IR (nujol): 3390, 2220, 1637 cm-1.

NMR (DMSO-d6) : 6,3 an 8.4 (4H, sh), 6,46 (1H, DD, J = 2,8 Hz, 3.9 Hz), 7,24 (1H, DD, J = 1.6 Hz, 3.9 Hz), 7,56 (1H, DD, J = 1.6 Hz, 2.8 Hz), 7,58-of 7.69 (2H, m), 8,11-8,19 (2H, m).

(2) 2-[3-(3-Cyanoprop-1-yl)benzoyl]guanidine

So pl. 203-205oC.

IR (nujol): 3420, 3300, 3140, 2220, 1655, 1630, 1660 cm-1.

NMR (DMSO-d6) : from 6.4 to 8.2 (4H, sh), 6,72-7,76 (1H, m), 7,47 to 7.75 (3H, m), 8-8,1 (1H, m), 8,18-8,23 (2H, m).

(3) 2-[3-(2-Benzyloxycarbonylamino-1-yl)benzoyl]guanidine

IR (film): 3400, 1705, 1630 cm-1.

NMR (DMSO-d6) : 5,12 (2H, s), 6,28-8,35 (4H, sh), 6,34 (1H, DD, J = 2.7 Hz, 3.9 Hz), and 7.1 (1H, DD, J = 1,8 Hz, 3.9 Hz), 7,2-7,51 (8H, m), 7,98-8,02 (1H, m), 8,03-of 8.09 (1H, m).

(4) 2-[4-Phenylbenzyl]guanidine hydrochloride

So pl. 270-272oC.

IR (nujol): 3300, 1685, 1260, 745 cm-1.

NMR (DMSO-d6) : 7,4-the 7.65 (3H, m), 7,7-7,9 (2H, m), 7,92 (2H, d, J = 8.5 Hz), compared to 8.26 (2H, d, J = 8.5 Hz), 8,63 (2H, s), 8,84 (2H, s), 12,14 (1H, s).

MACC (m/z): 240 (M+1).

Example 16.

By the method similar to the method of example 6, the following compounds:

(1) 2-[3-[(Z)-2-Gidroksiiminobetulonovoi-1-yl]benzoyl]-guanidine ghidrah the 6,36-6.42 per (1H, m), 7,11 (1H, s), 7,28 and 7.36 (2H, m), 7,72-7,81 (1H, m) to 8.12 (1H, s), 8,19-of 8.25 (1H, m), 8,72 (2H, s), 8,79 (2H, s), 12,36 (1H, s).

MASS (m/z 272 (M++1 of free base).

(2) 2-3-[(E)-2-Gidroksiiminobetulonovoi-1-yl] benzoyl] -guanidine hydrochloride

So pl. 207-208oC.

IR (nujol): 3250, 3100, 1695 cm-1.

NMR (DMSO-d6) : 6,36-6.42 per (1H, m), to 7.09 (1H, s), 7,25-to 7.35 (2H, m), 7,73-of 7.82 (2H, m), 8,08 (1H, s), 8,15 is 8.22 (1H, c), 8,5-8.82 (4H, m), 11,47 (1H, s), 12,17 (1H, s).

Mass (m/z): 272 (M++1 of free base).

(3) 2-[3-(2-Dimethylaminomethylene-1-yl] benzoyl] -the guanidine dihydrochloride

So pl. 210-211oC.

IR (nujol): 3350, 3080, 1690-1705 (W.), 1630 cm-1.

NMR (DMSO-d6) : 2,49 (6H, s), 4,32 (2H, s), 6,32-6,38 (1H, m), 6,7-of 6.75 (1H, m), 7,2-of 7.25 (1H, m), 7.68 per-7,8 (2H, m), 8,15-of 8.25 (2H, m), 8,76 (2H, s) 8,89 (2H,c), 10,49 (1H, c), 12,56 (1H, c).

MASS (m/z); 286 (M+1 of free base).

(4) 2-[3-(2,5-Dichloroprop-1-yl)benzoyl]guanidine hydrochloride

So pl. 204-205oC.

IR (nujol): 3330, 3240, 3100, 1685 cm-1.

NMR (DMSO-d6) : 6,41 (2H, c), 7,71-7,89 (2H, m), of 8.06 (1H, s) of 8.37 (1H, d, J = 7,3 Hz), 8,67 (2H, s) 8,71 (1H, s), and 12.2 (1H, s).

Mass (m/z): 297 (M++1) of free base).

(5) 2-[3-(2-Carbamoylphenoxy-1-yl)benzoyl]guanidine hydrochloride

So pl. 155-158oC. 2H, W), 6,97 (1H, DD, J= 1.6 Hz), 7.23 percent-7,28 (1H, m), 7,54 - to 7.67(2H, m), 8,01 (1H, s), 8.07-a of 8.15 (1H, m), 8,66 (2H, s), 8,77 (2H, s), 12,22 (1H, s).

Mass (m/z): 272 (M++1) of free base).

(6) 2-[3-(2-Acetylpyrrole-1-yl)benzoyl]guanidine hydrochloride

So pl. 87-89oC.

IR (nujol): 3100-3300, (W), 1690, 1630 cm-1.

NMR (DMSO-d6) : 2,43 (3H, c), of 6.68 (1H, dd, J=1.6 Hz), 7.68 per-7,79 (2H, m), to 7.99 (1H, d, J = 8.1 Hz), 8.08 (1H, d, J= 8.1 Hz), 8,49-8,7(4H, s), 8,81 (2H, s), 12,38 (1H, s).

Mass (m/z): 271 (M++1) of free base).

(7) 2-[3-(2-Cyanoprop-1-yl)benzoyl]guanidine hydrochloride

So pl. 220-221oC.

IR (nujol): 3300, 3080, 1700, 1615, 1585 cm-1.

NMR (DMSO-d6) : of 6.52 (1H, DD, J= 2,9 Hz), and 7.3 (1H, DD, J= 1.5 Hz, 3.9 Hz), 7,75-7,88 (2H, m), to $ 7.91 shed 8.01 (1H, m), 8,18 compared to 8.26 (1H, m), 8,3-to 8.34 (1H, m), 8,65 (2H, s), 8,77 (2H, s) 12,42 (1H, s).

Mass (m/z): 254 (M++1 of free base).

(8) 2-[3-(3-Cyanoprop-1-yl)benzoyl]guanidine hydrochloride

So pl. 259-261oC.

IR (nujol): 3350, 3100, 2230, 1700, 1610, 1590 cm-1.

NMR (DMSO-d6) : 6,79 (1H, DD, J= 1.5 Hz), of 7.75 (1H, DD, J= 8 Hz), 7,8-a 7.85 (1H, m), 7,99 to 8.1 (2H, m), 8,43-8,51 (2H, m), 8,56 (1H, s), is 8.75 (2H, s), 12,35 (1H, s).

Mass (m/z): 254 (M++1 of free base).

(9) 2-[4-n-Butyl-3-(2-sienopyr-1-yl)benzoyl]-guanidine hydrochloride

of 1.05 to 1.27 (2H, m), from 1.3 to 1.45 (2H, m), 2,39 is 2.55 (2H, m), 6.48 in (1H, DD, J= 2.7 Hz, 4 Hz), 7,24 (1H, DD, J= 1.6 Hz, 4 Hz), 7,44 (1H, DD, J= 1.6 Hz, 2.7 Hz), 7,74 (1H, d, J= 8.1 Hz), was 7.08 (1H, d, J = 1,8 Hz), 8,29 (1H, DD, J= 1,8 Hz), 8.1 Hz), of 8.47-8,75 (4H, m), compared to 12.1 (1H, s).

Mass (m/z): 310 (M++1 of free base).

(10) 2-[4-n-Butyl-3-(pyrrol-1-yl)benzoyl]guanidine hydrochloride

So pl. 188o-189oC.

IR (nujol): 3370, 3260, 1700, 1670, 1610 cm-1.

NMR (DMSO-d6) : of 0.77 (3H, t, J= 7,1 Hz), 1.06 a-a 1.45 (4H, m), a 2.5 to 2.65 (2H, m), 6,24-6,28 (2H, m), 6,98-7,03 (2H, m), to 7.61 (1H, d, J = 8.1 Hz), of 7.97 (1H, s) to 8.12 (1H, d, J = 8.1 Hz), 8,64 (2H, s), is 8.75 (2H, s), 12,17 (1H, s).

Mass (m/z): 285 (M++1 of free base).

(11) 2-[4-Methyl-3-(pyrrol-1-yl)benzoyl]guanidine hydrochloride

So pl. 251-252oC.

IR (nujol): 3400, 3250, 3130, 2230, 1700, 1610 cm-1.

NMR (DMSO-d6) : 2,3 (3H, s), 6,24-6,3 (2H, m), 7,05-7,11 (2H, m), and 7.6 (1H, d J= 8.1 Hz), 7,98 (1H, d, J=1,8 Hz), with 8.05 (1H, DD, J= 1,8 Hz, 8.1 Hz), 8,59 (2H, s) 8,71 (2H, s), 12,11 (1H, s).

Mass (m/z: 243 (M++1 of free base).

(12) 2-[5-Cyano-3-(pyrrol-1-)benzoyl]guanidine hydrochloride

So pl. 267-268oC.

IR (nujol): 3400, 3250, 3130, 2230, 1700, 1610 cm-1.

NMR (DMSO-d6) : 6,33-6,38 (2H, m), 7,72 for 7.78 (2H, m), of 8.25 (1H, s), and 8.5 (1H, s), 8,65 (2H, s), 8,72 (1H, s), 8,79 (2H, s), br12.62 (1H, s).

Mass (m/z): 254 (M++1 is the ethanol (20 ml) is added conc. sulfuric acid (0,42 ml) and the mixture is stirred for 30 minutes at room temperature. Then to the mixture is added ethyl acetate (20 ml) and the resulting precipitate is filtered off. By recrystallization of the precipitate from methanol-water get polysulphate 2-[3-(2-cyanoprop-1-yl)benzoyl]guanidine (1,53 g).

So pl. 170-171oC.

IR (nujol): 3300, 3110, 2220, 1720, 1690, 1610, 1100 cm-1.

NMR (DMSO-d6) : 6,48 (1H, DD, J= 2,8 Hz, 3.9 Hz), 7-8,4 (4H, sh), 7,27 (1H, DD, J= 1.6 Hz, 3.9 Hz), to 7.61 (1H, DD, J= 1.6 Hz, 2.8 Hz), 7,66-to 7.84 (2H, m), 8.07-a to 8.14 (2H, m).

Example 18.

To a solution of 2-[3-(2-cyanoprop-1-yl)benzoyl]guanidine (1 g) in methanol (10 ml) add a solution of fumaric acid (0,46 g) in methanol (10 ml) and everything is stirred for 1 hour at room temperature. The formed precipitate is filtered off and, after recrystallization from aqueous methanol receive fumarate 2-[3-(2-cyanoprop-1-yl)benzoyl]guanidine (1,03 g).

So pl. 216-217oC.

IR (nujol): 3360, 3130, 2220, 1730, 1705, 1610 cm-1.

NMR (DMSO-d6) : 6,46 (1H, DD, J= 2,8 Hz, 3.9 Hz), 6,55 to 8.6 (4H, sh), of 6.61 (2H, s), from 7.24 (1H, DD, J=1.6 Hz, 3.9 Hz), EUR 7.57 (1H, DD, J = 1.6 Hz, 2.8 Hz), to 7.61 -7,71 (2H, m), 8,11-8,19 (2H, m).

Example 19.

According to the methods similar to the methods of examples 6, 17 and 18, the following soedineniya, 2220, 1700, 1610, 1590 cm-1.

NMR (DMSO-d6) : 2,55-2,77 (2H, m), 6,47 (1H, DD, J = 2,8 Hz, 3.9 Hz), 6,77 and 8.6 (4H, sh), from 7.24 (1H, DD, J = 1.6 Hz, 3.9 Hz), 7,56 (1H, DD, J = 1.6 Hz, 2.8 Hz), to 7.59 to 7.75 (2H, m), 8,1-8,19 (2H, m).

(2) 2-[3-(2-Cyanoprop-1-yl)benzoyl]guanidine maleate

So pl. 211-213oC.

IR (nujol): 3400, 3250, 3100, 2220, 1705, 1685 cm-1.

(DMSO-d6) : 6,1 (2H, c), 6,51 (1H, DD, J = 2,8 Hz, 3.9 Hz), 7,29 (1H, DD, J = 1,6, 3,9 Hz), a 7.62 (1H, DD, J = 1.6 Hz, 2.8 Hz), and 7.8 (1H, DD, J = 8,2 Hz and 8.2 Hz), the 7.85-7,94 (1H, m), 8,04-to 8.12 (2H, m), 8,19 (4H, m).

Example 20.

To a solution of 2-[3-(2-cyanoprop-1-yl)-5-(diaminotrinitrobenzene) benzoyl]guanidine (0.8 g) in methanol (16 ml) is added methanesulfonyl acid (0.5 ml) and everything is stirred for 1 hour at room temperature. The formed precipitate is filtered off and recrystallization from water getting 2-[3-(2-cyanoprop-1-yl)-5- (diaminotrinitrobenzene)benzoyl]guanidine dimethanesulfonate (0.65 g).

So pl. 250-251oC.

IR (nujol): 3350, 3100, 2220, 1725, 1600, 1210, 1050 cm-1.

(DMSO-d6) : 2,43 (6H, c), to 6.57 (1H, DD, J = 2,9 Hz, 3.9 Hz), was 7.36 (1H, DD, J = 1.6 Hz, 3.9 Hz), to 7.77 (1H, DD, J = 1.6 Hz, 2.9 Hz), of 8.3 to 8.8 (4H, m), to 8.41 (2H, c), 8,55 (1H, c), 11,67 (2H, c).

MASS (m/z): 339 (M++1 of free base).

Example 21.

According to the method unloadcontent

So pl. 200-201oC.

IR (nujol): 3350, 3100, 2220, 1720, 1585, 1165, 1045 cm-1.

NMR (DMSO-d6) : a 2.36 (3H, c), of 6.49-6,55 (1H, m), 7,27-7,33 (1H, m), of 7.64-to 7.67 (1H, m), to 7.84 (1H, DD, J = 7,7 Hz, 7.7 Hz), of 7.96 (1H, d, J = 7,7 Hz), 8-8,1 (2H, m), 8,2-8,6 (4H, m), 11,42 (1H, c).

(2) 2-[3-(Pyrrol-1-yl)benzoyl]guanidine methanesulfonate

So pl. 216oC.

IR (nujol): 3350, 3150, 1700, 1695, 1180, 1050 cm-1.

NMR (DMSO-d6) : of 2.38 (3H, c), of 6.31-6,36 (2H, m), 7,45 is 7.5 (2H, m), of 7.69 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,79 (1H, d, J = 7.8 Hz), 7,95 (1H, d, J = 7.8 Hz), 8,07 (1H, c), and 8.4 (4H, c), is 11.39 (1H, c).

Example 22.

To a solution of 2-[3-nitro-5-(pyrrol-1-yl)benzoyl]guanidine (0.3 g) in a mixture of methanol (10 ml) with tetrahydrofuran (5 ml) is added 10% palladium on coal (50% in water) and all hydronaut at room temperature and atmospheric pressure. The catalyst is filtered off and the filtrate evaporated in vacuum. The residue is dissolved in ethanol and after processing a small excess of 4 n solution of hydrogen chloride in ethyl acetate to obtain the dihydrochloride of 2-[3-amino-5-(pyrrol-1-yl)benzoyl]guanidine (310 mg).

So pl. 269-270oC (decomp.).

IR (nujol): 3340, 1685, 1355, 715 cm-1.

NMR (DMSO-d6) : 6,29 of 6.31 (2H, m), 7,37-7,41 (2H, m), 7,52-7,56 (2H, m), 8-8,05 (1H, m), 8,65 (2H, sh), 8,88 (2H, sh), of 12.33 (1H, sh).

MASS (m/z: 244 (M+1).

So pl. 213oC.

IR (nujol): 3270, 1690 cm-1.

NMR (DMSO-d6) : 6,15 to 6.5 (4H, m), of 6.29 (1H, DD, J = 2.7 Hz, 3.8 Hz), of 6.99 (1H, DD, J = 1,8 Hz, 3.8 Hz), 7,17 (1H, DD, J = 1,8 Hz, 2.7 Hz), of 7.36-7,51 (2H, m), 7,97-of 8.09 (2H, m).

MASS (m/z): 273 (M++1).

Example 24.

To a mixture of guanidine hydrochloride (of 2.26 g) and 28% methanolic solution of sodium methoxide (4,1 ml) in N,N-dimethylformamide (17 ml) is added methyl ether 3-(3-triftormetilfullerenov)benzoic acid (1.7 g) and the reaction mixture is stirred for 6 hours at room temperature. After evaporation of the solvent the residue is transferred into a mixture of ethyl acetate (50 ml) with water (50 ml). By adding 10% hydrochloric acid, the mixture is acidified to a pH of 6.2. The crystalline product is filtered off, washed successively with water and methanol is.sq. 259-260oC.

IR (nujol): 3375, 3250, 1705, 1010 cm-1.

NMR (DMSO-d6)::? 7.04 baby mortality-to 7.32 (4H, m), to 7.67 (1H, DD, J = 8 Hz, 7.5 Hz), 7,87-to 7.93 (2H, m) to 8.12 (1H, c), 8,23 (4H, c).

(+) APCI MASS (m/z): 387 /M+H/+.

Example 25.

According to the methods similar to the methods of examples 1, 3, 8, 10, 14 and 24, the following connections:

(1) 2-[2-Methoxy-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. 208-209oC.

IR (nujol): 3400, 1662, 1590 cm-1.

(DMSO-d6) : of 3.75 (3H, c), with 6.1 and 8.3 (4H, sh), 6,18-6,24 (2H, m), 7,03 (1H, d, J = 8.6 Hz), 7.18 in-7,24 (2H, m), 7,38-7,51 (2H, m).

(2) 2-[2-Hydroxy-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. 191-193oC.

IR (nujol): 3370, 3180, 1668, 1610 cm-1.

NMR (DMSO-d6) : 6,18-6,24 (2H, m), 6,7-8,9 (4H, sh), 6,87 (1H, d, J = 8.7 Hz), 7,14-of 7.2 (2H, m), of 7.48 (1H, DD, J = 3 Hz, 8.7 Hz), 7,86 (1H, d, J = 3 Hz), 14,75 (1H, c).

(+) APCI MASS (m/z): 245 /M+H/+.

Elemental analysis for C12H12N4O2< / BR>
Calculated: C 59,01, H 4,95, N 22,94

Found: C 59,16, H 5,04, N 22,59

(3) 2-[-Nitro-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. 212-213oC.

IR (nujol): 3420, 1655, 1600, 1585, 1355 cm-1.

NMR (DMSO-d6) : 6,2-8,5 (4H, sh), 6,32-6,38 (2H, m), 7,51-EUR 7.57 (2H, m), 7,76 (1H, DD, J = 2,5 Hz, 8.7 Hz), 7,83 (1H, d, J = 2.5 Hz), 7,95 (1H, d, J = 8.7 Hz).

(4)80, 1655, 1610 cm-1.

NMR (DMSO-d6) : of 2.09 (3H, c), from 6.4 to 8.3 (4H, sh), 6,53 (1H, DD, J = 1.6 Hz, 2.9 Hz), 7,31 and 7.36 (1H, m), of 7.48 (1H, DD, J = 7.8 Hz, 7.8 Hz), to 7.61 -7,65 (1H, m), 7,65 - 7,72 (1H, m), 7,95 (1H, d, J = 7.8 Hz), 8,18 (1H, s), 10.56 (1H, s).

(+) APCI MASS (m/z): 286 /M + H/+.

Elemental analysis for C14H15N5O2< / BR>
Calculated: C 58,94, 5,30 H, N RUB 24.55

Found: C 58,90, H of 5.45, N 24,27

(5) 2-[3-[2-((Z)-1-Hydroxyimino)pyrrol-1-yl]-benzoyl]-guanidine

So pl. 195-197oC (decomp.).

IR (nujol): 3360, 1600 cm-1.

NMR (DMSO-D6) : 2,11 (3H, s), 6,4 - 6,84 (4H, sh), 6,72 (1H, DD, J = 1.5 Hz, 2.9 Hz), 7,34 - 7,39 (1H, m), and 7.5 (1H, DD, J = 7.8 Hz, 7.8 Hz), of 7.64 - 7,71 (1H, m), 7,95 - of 8.04 (2H, m), 8,17 (1H, m).

(6) 2-[3-(2-Methoxyaminomethyl-1-yl)benzoyl] -guanidine methanesulfonate

So pl. 162-164oC.

IR (nujol): 3350, 1715, 1695, 1170, 1045 cm-1.

NMR (DMSO-d6) : 2,39 (3H, s), 3.7 and 3,93 (total 3H, each s), 6,35 - 6,46 (1H, m), of 6.71 - 6.75 in and 7,21 - 7,29 (total 2H, each m), 7.1 and a 7.92 (total 1H, each s), 7,72 - of 8.06 (4H, m), scored 8.38 (2H, s), charged 8.52 (2H, s), 11,37 (1H, s).

Elemental analysis for C14H15N5O2CH4O3S:

Calculated: C is 47.24, H 5,02, N 18,36

Found: C 47,31, H 4,73, N 18,07

(7) 2-[3-[2-(((E)-2-Carboxyethyl)pyrrol-1-yl)-benzoyl]guanidine

So pl. 204 - 206oC.

,97 - 7,02 (1H, m), 7,17 (1H, d, J = 15.7 Hz), 7,2 - of 7.25 (1H, m), 7,41 - 7,49 (1H, m), to 7.59 (1H, DD, J = 7,7 Hz, 7.7 Hz), 8,01 (1H, s), 8,16 (1H, d, J = 7,7 Hz).

(+) APCI MASS (m/z): 299 /M+H/+.

(8) 2-[3-[2-(2-Carboxyethyl)pyrrol-1-yl]-benzoyl]guanidine

So pl. 221oC.

IR (nujol): 3470, 3380, 1695, 1585 cm-1.

NMR (DMSO-d6) : 2,43 (2H, t, J = 7 Hz), a 2.71 (2H, t, J = 7 Hz), 5,98 - 6,03 (1H, m), 6,07 - x 6.15 (1H, m), 6,3 - 8,4 (4H, m), 6,79 - 6,86 (1H, m), 7,41 - 7,58 (2H, m), 8-8,1 (2H, m).

(+) APCI MASS (m/z): 301 /M+H/+.

Elemental analysis for C15H16N4O3< / BR>
Calculated: C 59,99, H lower than the 5.37, N 18,66

Found: C 59,79, H 5,49, N 18,38

(9) 2-[5-(Pyrrol-1-yl)-3-sulfamoylbenzoyl]guanidine

So pl. 173 - 174oC.

IR (nujol): 3350, 3230, 1628, 1365 cm-1.

NMR (DMSO-d6) : 6,32 - 6,38 (2H, m), from 6.4 to 8.7 (4H, sh), 7,35 - 7,41 (2H, m), 7,46 (2H, s), 8 - 8,05 (1H, m), 8,31 - at 8.36 (1H, m), of 8.37 - 8,42 (1H, m).

(10) 2-[3-(Pyrrol-1-)-5-(1H-tetrazol-5-yl)benzoyl]guanidine

So pl. 270oC.

IR (nujol): 3350, 3100, 1700, 1650, 1597 cm-1.

NMR (DMSO-d6) : 6,32 - 6,38 (2H, m), 7,15 - 8,5 (4H, sh), 7,42 - of 7.48 (2H, m), 8,18 is 8.22 (1H, m), 8,27 - 8,32 (1H, m), 8,56 and 8.6 (1H, m).

(+) APCI MASS (m/z): 297 /M+H/+.

Elemental analysis for C13H12N8O

Calculated: C 52,7, H 4,08, N 37,82

Found: C 52,6, H 3,98, N 37,46

1600 cm-1.

NMR (DMSO-d6) : 3,65 - of 3.77 (2H, m), of 4.13 (2H, t, J = 4.9 Hz), a 4.86 (1H, t, J = 5,2 Hz), 6,16 - to 6.22 (2H, m), from 6.4 to 8.3 (4H, sh), a 7.1 to 7.15 (2H, m), 7,19 (1H, d, J = 8.6 Hz), of 7.96 (1H, DD, J = 2.1 Hz, 8.6 Hz), 8,01 (1H, d, J = 2.1 Hz).

(12) 2-[4-Benzyloxy-3-pyrrol-1-yl)benzoyl]guanidine

So pl. 150 - 153oC.

IR (nujol): 3320, 1630, 1600 cm-1.

NMR (DMSO-d6) : to 5.21 (2H, s), 6,16 - 6,24 (2H, m), 6,3 - 6,84 (4H, sh), 7,02 - was 7.08 (2H, m), 7,27 - 7,47 (6H, m), 7,94 - of 8.06 (2H, m)

(13) 2-[4-Methoxy-3-(pyrrol-1-yl)benzoyl]guanidine

So pl. 155 - 156oC.

IR (nujol): 3450, 3320, 1660, 1633, 1695 cm-1.

NMR (DMSO-d6) : of 3.85 (3H, s), 6,16 - to 6.22 (2H, m), 6.3 to 8.3 (4H, sh), of 6.96 - 7,02 (2H, m), 7,19 (1H, d, J = 9,2 Hz), of 7.96 - of 8.06 (2H, m).

(14) 2-[4-Carboxymethoxy-3-(pyrrol-1-yl)benzoyl]guanidine

So pl. 250 - 253oC.

IR (nujol) : 3300, 1708, 1675, 1600 (sh.) cm-1< / BR>
NMR (DMSO-d6) : with 4.64 (2H, s), 6,16 - 6,23 (2H, m), from 6.4 to 9.4 (4H, sh), 6,98 (1H, d, J = 8,8 Hz), 7,17 - of 7.23 (2H, m), 7.9 (1H, DD, J = 2 Hz and 8.8 Hz), 8,01 (1H, d, J = 2 Hz),

(+) APCI MASS (m/z): 303 /M+H/+.

(15) 2-[3-Dimethylcarbamoyl-5-(pyrrol-1-yl)benzoyl] guanidine methanesulfonate

So pl. 203 - 204oC.

IR (nujol): 3350, 3280, 1710, 1630. 1590 cm-1.

NMR (DMSO-d6) : to 2.42 (3H, s), 2,95 (3H, s), 3.04 from (3H, s), 6,3 - 6,4 (2H, m), and 7.5 and 7.6 (2H, m), of 7.75 (1H, s), 7,98 (1H, s), 8,13 (1H, t, J = 1,8 Hz), 8,42 (2H, sales for C15H17N5O2CH4O3S :

Calculated: C 48,60, H 5,35, N 17,71

Found: C 48,27, H 5,32, N 17,47

(16) 2-[4-Acetamidomethyl-3-(pyrrol-1-yl)benzoyl]guanidine

So pl. 183 - 185oC.

IR (nujol): 3400, 3320, 3180, 1640, 1590 cm-1.

NMR (DMSO-d6) : of 1.87 (3H, c), of 4.12 (2H, d, J = 5.6 HZ), 6,21 - 6,27 (2H, m), 6,83 - 6,99 (2H, m), 7,41 (1H, d, J = 8 Hz), 7,98 (1H, s), 8,02 (1H, d, J = 8 Hz), of 8.28 (1H, t, J = 5.6 Hz).

(17) 8-(Diaminomethylene)-1-dimethylaminomethyl-4,4 - dimethyl-4H-pyrrolo/2,1-C//1.4/benzoxazin

So pl. 182 - 186oC.

IR (nujol): 3400, 1660, 1600 cm-1.

NMR (DMSO-d6) : of 1.53 (6H, s) to 2.29 (6H, s), 3,37 (2H, s), 6,01 (1H, d, J = 3,4 Hz), x 6.15 (1H, d, J = 3,4 Hz), 6,3 - 8,4 (4H, sh), of 6.99 (1H, d, J = 8,4 Hz), 7,86 (1H, DD, J = 1.7 Hz, 8,4 Hz), the rate of 8.75 (1H, d, J = 1.7 Hz).

(18) 2-[4-(Pyrrol-1-yl)benzoyl]guanidine

So pl. 184 - 186oC.

IR (nujol): 3300, 1595 cm-1.

NMR (DMSO-d6) : 6,1 - a 8.4 (4H, sh), 6,26 - 6,32 (2H, m), 7,41 -7,47 (2H, m), to 7.59 (2H,d, J = 8,8 Hz), 8,13 (2H, d, J = 8,8 Hz).

(19) 2-[3-[(Pyrrol-1-yl)methyl]benzoyl]guanidine

So pl. 165 - 166oC.

IR (nujol): 3430, 3280, 1647, 1600 cm-1.

NMR (DMSO-d6) : of 5.11 (2H, s), 5,99 - 6,05 (2H, m), a 6.2 to 8.4 (4H, sh), 6,76 - PC 6.82 (2H, m), 7,22 (1H, d, J = 7.5 Hz), 7,33 (1H, DD, J = 7.5 Hz, 7.5 Hz), 7,92 (1H, c), 7,98 (1H, d, J = 7.5 Hz).

(20) 2-[3tx2">

NMR (DMSO-d6) : from 6.4 to 8.8 (4H, sh), of 6.68 (1H, s), 7,41 (1H, DD, J = 7.2 Hz, 7.2 Hz), and 7.8 (1H, s), a 7.85 (1H, d, J = 7,2 Hz), 7,98 (1H, d, J = 7,2 Hz), 8,53 (1H, s), and 12.9 (1H, s).

(21) 2-[3-(Pyrimidine-4-yl)benzoyl]guanidine

So pl. 173-175oC.

IR (nujol): 3320, 3150, 1680, 1605, 1575 cm-1.

NMR (DMSO-d6) : a 6.2 to 8.7 (4H, sh), to 7.59 (1H, DD, J = 7,7 Hz, 7.7 Hz), and 8.1 (1H, d, J = 5.4 Hz), and 8.2 to 8.3 (2H, m), 8,86-8,95 (2H, m), 9.28 are (1H, c).

(22) 2-[3-(Pyridin-2-yl)benzoyl]guanidine

So pl. 190-191oC.

IR (nujol): 3310, 3140, 1670, 1605, 1585, 1570 cm-1.

NMR (DMSO-d6) : of 6.3 and 8.6 (4H, sh), 7,31-the 7.43 (1H, m), 7,51 (1H, DD, J = 7,7 Hz, 7.7 Hz), 7,83-to 7.99 (2H, m), 8,08-8,18 (2H, m), 8,65-8,73 (1H, m), 8,78-8,84 (1H, m).

(23) 2-[3-(Pyridin-3-yl)benzoyl]guanidine.

So pl. 182-185oC.

IR (nujol): 3430, 3290, 1690, 1670, 1625 cm-1.

NMR (DMSO-d6) : of 6.3 and 8.6 (4H, sh), 7,46-7,58 (2H, m), 7,76-7,83 (1H, m), 8,02-of 8.15 (2H, m), 8,35-to 8.41 (1H, m), 8,56-to 8.62 (1H, m), cent to 8.85-8,89 (1H, m).

(24) 2-[3-(5-Aminopyrazole-1-yl)benzoyl]guanidine

So pl. 140-143oC.

IR (nujol): 3320, 3180, 1645 cm-1.

NMR (DMSO-d6) : 5,3 (2H, c), of 5.48 (1H, d, J = 1,8 Hz), 6,2-or 8.6 (4H, sh. ), 7,29 (1H, d, J = 1,8 Hz), 7,47 (1H, DD, J = 7.8 Hz, 7.8 Hz), to 7.61-of 7.69 (1H, m), 7,95-8,02 (1H, m), 8,27-8,32 (1H, m).

(25) 2-[3-(1H-tetrazol-5-yl)benzoyl]guanidine

So pl. >300oC.

IR (nujol): 3300, 310 (1H, c).

(+) APCI MASS (m/z): 232 /M+H/+.

(26) 2-[3-(3-Cyano-1,5-dimethylpyrrole-2-yl)benzoyl]guanidine

So pl. 112-124oC.

IR (nujol): 3320, 3350, 1662, 1640, 1610, 1590 cm-1.

NMR (DMSO-d6) : of 2.26 (3H, c), of 3.45 (3H, c), a 6.2 to 8.4 (4H, m), 7.5 to a 7.62 (2H, m), of 8.1 to 8.2 (2H, m).

(27) 2-[2-(Pyrrol-1-yl)isonicotinoyl]guanidine

So pl. 165 to 169oC.

IR (nujol): 3440, 3350, 3070, 1685, 1625, 1605 cm-1.

(DMSO-d6) : 6,29 to 6.35 (2H, m), 6.5 to 8.9 in (4H, sh), 7,63-of 7.69 (2H, m), 7,71-to 7.77 (1H, m), of 8.06 (1H, c), 8,45-charged 8.52 (1H, m).

(28) 2-[[4-(Pyrrol-1-yl)pyridine-1-yl]carbonyl]guanidine

So pl. 176-180oC.

IR (nujol): 3320, 3100, 1663, 1584 cm-1.

NMR (DMSO-d6) : a 6.2 to 8.7 (4H, sh), 6,34 is 6.4 (2H, m), 7,55-to 7.61 (2H, m), and 7.7 (1H, DD, J = 2.2 Hz, 5.4 Hz), and 8.2 (1H, d, J = 2.2 Hz), 8,58 (1H, d, J = 5.4 Hz).

(29) 2-[3-(3-Were)benzoyl]guanidine hydrochloride

So pl. 168-169oC.

IR (nujol): 1690, 1300, 1250 cm-1.

NMR (DMSO-d6) : 2,4 (3H, c), from 7.24 (1H, d, J = 7,4 Hz), 7,39 (1H, DD, J = 7,6 Hz and 7.6 Hz), 7,6 to 7.75 (3H, m), 7,95-of 8.15 (2H, m), of 8.47 (1H, c), 8,63 (2H, sh.c) 8,89 (2H, sh.c) to 12.3 (1H, c).

(+) APCI MASS (m/z): 254 /M of the free base + H/+.

(30) 2-[3-[(2-Forfinal)benzoyl]guanidine hydrochloride

So pl. 168-169oC.

IR (nujol): 3350, 3150, 1700, 1685, 1235 cm-1.

Elemental analysis for C14H12FN3HCl

Calculated: C 56,55, H of 4.54, N 14,13

Found: C 56,65, H 4,43, N 14,15

(31) 2-[3-(3-Nitrophenyl)benzoyl]guanidine hydrochloride

So pl. 239-240oC.

IR (nujol): 3325, 1690, 1520, 1360 cm-1.

NMR (DMSO-d6) : of 7.7 to 7.9 (2H, m), of 8.1 to 8.2 (2H, m), and 8.2 and 8.3 (1H, m), 8,3 an 8.4 (1H, m), 8.4 to 8.9 in (6H, m), 12,31 (1H, c).

(+) APCI MASS (m/z): 285 /M free base + H/+.

(32) 2-[3-(2-Nitrophenyl)benzoyl]guanidine hydrochloride

So pl. 206-208oC.

IR (nujol): 3350, 1700, 1590, 1520, 1230 cm-1.

NMR (DMSO-d6) : to 7.67-7,88 (5H, m), 8,05-8,23 (3H, m), 8,59 (2H, sh.c) 8,73 (2H, sh.c), 12,17 (1H, c).

(+) APCI MASS (m/z): 285 /M free base + H/+.

(33) 2-[3-(3-Cyanophenyl)benzoyl]guanidine hydrochloride

So pl. 268oC (decomp.).

IR (nujol): 3350, 2230, 1700, 1560 cm-1.

NMR (DMSO-d6) : to 7.67-to 7.77 (2H, m), and 7.9 (1H, d, J = 7,8 Hz) to 8.12 (2H, d, J = 7.8 Hz), of 8.27 (1H, d, J = 7.8 Hz), and 8.4 (1H, c), 8,59 (1H, c), 8,61 (2H, sh.c), cent to 8.85 (2H, sh.c) and 12.4 (1H, c).

(+) APCI MASS (m/z): 265 /M free base + H/+.

(34) 2-[3-(2-Chlorophenyl)benzoyl]guanidine hydrochloride

So pl. 191-192oC.

IR (nujol): 3200, 1690, 1560, 1230 cm-1.

NMR (DMSO-d6) : 7,44-7,74 (5H, m), 7,82 (1H, d is + H/+.

Elemental analysis for C14H12ClN3OHCl

Calculated: C 54,21, H 4,22, N 13,55

Found: C 54,11, H 4,24, N 13,42

(35) 2-[3-(3-Forfinal)benzoyl]guanidine hydrochloride

So pl. 214-216oC.

IR (nujol): 3100, 1690, 1270 cm-1.

NMR (DMSO-d6) : 7,22-7,31 (1H, m), 7,49-to 7.84 (4H, m), 8,05-8,13 (2H, m), 8,54 (1H, c) 8,64 (2H, sh.c) 8,89 (2H, sh.c), 12,41 (1H, c).

(+) APCI MASS (m/z): 258 /M free base + H/+.

(36) 2-[3-(4-Forfinal)benzoyl]guanidine hydrochloride

So pl. 160-162oC.

IR (nujol): 3120, 1700, 1630, 1260 cm-1.

NMR (DMSO-d6) : 7,29-7,38 (2H, m), of 7.69 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,9-of 8.09 (4H, m), of 8.47 (1H, c), 8,61 (2H, sh.c) 8,86 (2H, sh.c), 12,34 (1H, c).

(+) APCI MASS (m/z): 258 /M free base + H/+.

(37) 2-[3-(3-Triptoreline)benzoyl]guanidine hydrochloride

So pl. 179-181oC.

IR (nujol): 3300, 1690, 1640, 1150, 1110 cm-1.

NMR (DMSO-d6) : 7,69-of 7.82 (3H, m), 8,09-of 8.15 (2H, m), 8,2-8,23 (2H, m), 8,55 (1H, c), 8,59 (2H, sh.c) 8,82 (2H, sh.c), 12,37 (1H, c).

(+) APCI MASS (m/z): 308 /M free base + H/+.

(38) 2-[3-[((E)-2-carboxyethyl]-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. >250oC.

IR (nujol): 3300, 1690, 1580 cm-1.

NMR (DMSO-d6) : 6,2-6,4 (2H, mitarbeiterbeteiligung-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. >250oC.

IR (nujol): 3370, 1700, 1595 cm-1.

NMR (DMSO-d6) : 6,2-6,3 (2H, m), 7,2-7,3 (2H, m), between 7.4 to 7.5 (3H, m), 8,1 an 8.4 (4H, sh.c) 11,09 (1H, sh.c).

(+) APCI MASS (m/z): 376 /M+H/+.

(40) 2-[3-(Diethylaminoethylamine)-5-(pyrrol-1-yl)-benzoyl] the guanidine dihydrochloride

So pl. 188-195oC.

IR (nujol): 3200, 1700, 1590 cm-1.

NMR (DMSO-d6) : of 1.27 (6H, t, J = 7.2 Hz), the 3.2 and 3.4 (4H, m), 4,24 (2H, c), 6,3-6,4 (2H, m), and 7.5 and 7.6 (2H, m), 8,15 (1H, c), 8,18 (1H, c), scored 8.38 (1H, c), and 8.7 (2H, sh.c) of 8.92 (2H, sh.c) for 9.95 (1H, sh.c) 11,66 (1H, c), 12,57 (1H, c).

(+) APCI MASS (m/z): 357 /M free base + H/+.

(41) 2-[3-Morpholinosydnonimine)-5-(pyrrol-1-yl)benzoyl] guanidine the dihydrochloride

So pl. >250oC.

IR (nujol): 3320, 1690, 1615, 1580 cm-1.

NMR (DMSO-d6) : 3,1-3,6 (4H, m), 3.7 to 4.1 (4H, m), 4,27 (2H, c), 6,2-6,4 (2H, m), and 7.5 and 7.6 (2H, m), 8,11 (1H, c), 8,16 (1H, c), 8,35 (1H, c) 8,64 (2H, sh.c), 8,9 (2H, sh.c) to 10.7 (1H, sh.c) 11,43 (1H, c), of 12.53 (1H, c).

(+) APCI MASS (m/z): 371 /M free base + H/+.

(42) 2-[3-Dimethylaminomethyl-5-(pyrrol-1-yl)benzoyl] guanidine the dihydrochloride

So pl. >250oC.

IR (nujol): 3300, 1690, 1600 cm-1.

NMR (DMSO-d6) : 2,75 (6H, c), 4,43 (2H, c), 6,3-6,4 (2H, m), 7,7-7,8 (2H, m), 8,02 (1H, c), scored 8.38 (1H, c), and 8.6 (1H, c), 8,71 (1H, sh.c) 8,93 (1H, sh.c), and 11.2 (1H, sh.c), 12,67 (l)benzoyl]the guanidine dihydrochloride

So pl. 216-218oC.

IR (nujol): 3350, 1690, 1600 cm-1.

NMR (DMSO-d6) : 2,9-3,3 (4H, m), 6,2-6,4 (2H, m), and 7.6 to 7.7 (2H, m), 7,8-7,9 (2H, m), 8-8,3 (3H, m), with 8.33 (1H, c), 8,72 (2H, sh.c) 8,95 (2H, sh. c), and 12.6 (1H, c).

(+) APCI MASS (m/z): 272 /M free base + H/+.

(44) 2-[3-Gidroksilaminami-5-(pyrrol-1-yl) benzoyl]guanidine

So pl. 185-187oC.

IR (nujol): 3360, 3130, 1660, 1625, 1585 cm-1.

NMR (DMSO-d6) : 6,2-6,4 (2H, m), 7.3 to 7.4 (2H, m), and 7.7 to 8.3 (4H, m), is 11.39 (1H, c).

(+) APCI MASS (m/z): 272 /M+H/+.

(45) 2-[3-Hydroxymethyl-5-(pyrrol-1-yl)benzoyl]guanidine

So pl. 188-189oC.

IR (nujol): 3420, 3300, 3150, 1635, 1600 cm-1.

NMR (DMSO-d6) : 4,5-4,7 (2H, m), 5,2-5,4 (1H, m), 6,2-6,3 (2H, m), 7.3 to 7.4 (2H, m), and 7.5 and 7.6 (1H, c), of 7.9 to 8.1 (2H, m).

(+) APCI MASS (m/z): 259 /M+H/+.

(46) 1-Cyano-8-(diaminomethylene)-4,4-dimethyl-4H - pyrrolo/2,1-c//1,4/benzoxazine methanesulfonate

So pl. 276-278oC.

IR (nujol): 3330, 3160, 3100, 2210, 1712, 1694, 1610, 1597, 1195, 1040 cm-1.

NMR (DMSO-d6) : of 1.64 (6H, c), of 2.38 (3H, c), 6,47 (1H, d, J = 4 Hz), 7,39 (1H, d, J = 4 Hz), 7,41 (1H, d, J = 8.6 Hz), 7,9 (1H, DD, J = 2 Hz, 8.6 Hz), 8,39 (4H, c), 8,66 (1H, d, J = 2 Hz), to 11.31 (1H, c).

(+) APCI MASS (m/z): 310 /M free base + H/+.

Elemental analy,84, N 17,12

(47) 8-Diaminomethylene)-4H-pyrrolo/2,3-c//1,4/benzoxazine methanesulfonate

So pl. 232-233oC.

IR (nujol): 3330, 1695, 1585, 1170, 1045 cm-1.

NMR (DMSO-d6) : to 2.42 (3H, c), 5,31 (2H, c), 6,11-of 6.17 (1H, m), 6,33-6,4 (1H, m), 7,28 (1H, d, J = 8.5 Hz), EUR 7.57-the 7.65 (1H, m), 7,71 (1H, DD, J = 2.1 Hz, 8.5 Hz), 8,21 (1H, d, J = 2.1 Hz), 8,42 (4H, c), to 11.28 (1H, c).

(+) APCI MASS (m/z): 257 /M free base + H/+.

Elemental analysis for C13H12N4O2CH4O3S:

Calculated: C 47,72, H 4,58, N 15,90

Found: C 47,80, H 4,59, N 15,79

(48) 2-[3-Hydroxymethyl-5-phenylbenzyl]guanidine methanesulfonate

So pl. 129-130oC.

IR (nujol): 3350, 1690, 1170, 1040 cm-1.

NMR (DMSO-d6) : and 4.68 (2H, c), 7,4-7,6 (3H, m), 7,73 for 7.78 (2H, m), 7,9-of 7.95 (2H, m), of 8.09 (1H, c), 8,3-8,7 (4H, sh), 11,38 (1H, c).

(+) APCI MASS (m/z): 270 /M free base + H/+.

(49) 2-[3-Benzoylmethyl guanidine]methanesulfonate

So pl. 208-210oC.

IR (nujol): 3300, 1710, 1040, 700 cm-1.

NMR (DMSO-d6) : of 2.38 (3H, c), 7,56-a 7.85 (6H, m), 8,03-8,08 (1H, m), by 8.22 to 8.3 (2H, m), 8,2-8,7 (4H, sh), of 11.45 (1H, c).

(+) APCI MASS (m/z): 268 /M free base + H/+.

(50) 2-[3-Trifloromethyl]guanidine hydrochloride

So pl. 156-157oC.

(+) APCI MASS (m/z): 232 /M free base + H/+.

(51) 2-[3-(3-Chlorophenyl)benzoyl]guanidine methanesulfonate

So pl. 213-214oC.

IR (nujol): 3340, 3100, 1710, 1160 cm-1.

NMR (DMSO-d6) : 2,4 (3H, c), 7,49-to 7.61 (2H, m), 7.68 per-7,79 (2H, m), 7,86 (1H, c), of 7.97 (1H, d, J = 7.9 Hz), 8,07 (1H, d, J = 7.9 Hz), by 8.22 (1H, c), to 8.45 (4H, sh.c), 11,42 (1H, c).

(+) APCI MASS (m/z): 276 /M free base + H/+.

Elemental analysis for C14H12ClN3OCH3SO3H

Calculated: C 48,72, H 4,36, N 11,36

Found: C 48,74, H 4,40, N 11,22

(52) 2-[3-(Furan-3-yl)benzoyl]guanidine methanesulfonate

So pl. 214-216oC.

IR (nujol): 3350, 3100, 1690, 1590, 1260 cm-1.

NMR (DMSO-d6) : to 2.42 (3H, c), 7,07 (1H, DD, J = 1.6 Hz, 0.6 Hz), 7,63 (1H, DD, J = 7.8 Hz, 7.8 Hz), 7,8-a 7.85 (2H, m), of 7.97 (1H, d, J = 7.8 Hz), 8,15 (1H, DD, J = 1.6 Hz, 0.6 Hz), a 8.34 (1H, c), 8,46 (4H, sh.c), 11,38 (1H, c).

(+) APCI MASS (m/z): 230 /M free base + H/+.

Elemental analysis for C12H11N3O2CH3SO3H

Calculated: C 47,99, H 4,65, S 12,92

Found: C 48,17, H 4,75, S 12,46

(53) 2-[3-Hydroxy-5-phenylbenzyl]guanidine methanesulfonate

So pl. 287-288oC.

IR (nujol): 3300, 3150, 1700, 1600, 1340, 11.c), 10,22 (1H, c), 11,27 (1H, c).

(+) APCI MASS (m/z): 256 /M free base + H/+.

(54) 2-[3-(2-Hydroxyethoxy))-5-phenylbenzyl]guanidine methanesulfonate

So pl. 175-176oC.

IR (nujol): 3350, 3100, 1700, 1590, 1170 cm-1.

NMR (DMSO-d6) : 2,43 (3H, s), of 3.78 (2H, t, J = 4,8 Hz), 4,19 (2H, t, J = 4,8 Hz), 7,39 - of 7.55 (5H, m), 7,76 one - 7.8 (3H, m), 8,44 (4H, sh.C.), 11,36 (1H, s).

(+) APCI MACC (m/z): 300 /M free base + H/+.

(55) 2-[3-(2-Cyanothiophene-3-yl)benzoyl]guanidine methanesulfonate

So pl. 188 - 189oC.

IR (nujol): 3320, 2200, 1710, 1050 cm-1.

NMR (DMSO-d6) : of 2.38 (3H, s), to 7.68 (1H, d, J = 5,1 Hz), 7,82 (1H, DD, J = 7.8 Hz, 7.8 Hz), 8 - of 8.15 (2H, m), by 8.22 (1H, d, J = 5,1 Hz), 8,24 compared to 8.26 (1H, m), of 8.3 and 8.6 (4H, sh.C) 11,42 (1H, s).

(+) APCI MACC (m/z): 271 /M+H/+.

Elemental analysis for C13H10N4OSCH4O3S:

Calculated: C 45,89, H of 3.85, N 15,29

Found: C 45,81, H 3,74, N 15,13

(56) 2-[3-(2-Cianfuran-3-yl)benzoyl]guanidine methanesulfonate

So PL . 208oC (decomp.).

IR (nujol): 3300, 2220, 1720, 1170 cm-1.

NMR (DMSO-d6) : is 2.37 (3H, s), 7,38 (1H, d, J = 1.9 Hz), 7,81 (1H, DD, J = 7.8 Hz, 7.8 Hz), of 8.04 (1H, d, J = 7.8 Hz), 8,11 (1H, d, J = 7.8 Hz), 8,24 (1H, d, J = 1.9 Hz), of 8.28 (1H, DD, J = 1.7 Hz, 1.7 Hz), 8,43 (4H, sh.C) 11,44 (1H, s).

(+) APCI MACC (m/z): 244 /M+H/x2">

IR (nujol): 3390, 3280, 1694, 1665, 1575, 1237, 1028 cm-1.

NMR (DMSO-d6) : a 2.36 (3H, s), 6,18 - 6,24 (2H, m), of 6.99 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,07 - 7,13 (2H, m), and 7.4 (1H, DD, J = 1.5 Hz, 7.9 Hz), of 7.75 (1H, DD, J = 1.5 Hz, 7.9 Hz), and 7.8 and 8.6 (4H, sh).

Elemental analysis for C12H12N4O2CH4O3S:

Calculated: C 45,88, H 4,74, N 16,46

Found: C 46,04, H a 4.83, N 16,48

(58) 6-(Diaminomethylene)-4H-pyrrolo /2,1-c//1,4/-benzoxazine methanesulfonate

NMR (DMSO-d6) : 2,35 (3H, s) 5,38 (2H, s), 6,15 to 6.2 (1H, m), of 6.31 - to 6.39 (1H, m), 7,25 (1H, DD, J = 7.9 Hz, 7.9 Hz), 7,5 to 7.62 (2H, m), 7,98 (1H, DD, J = 1.5 Hz), 8,58 (4H, s) 11,05 (1H, s).

(59) 1-Cyano-6-(diaminomethylene)-4H-pyrrolo-/2,1-c//1,4/benzoxazine methanesulfonate

NMR (DMSO-d6) : a 2.36 (3H, s), 5,42 (2H, s), of 6.45 (1H, d, J = 4 Hz), 7,34 - 7,44 (2H, m), 7,68 (1H, DD, J = 1.4 Hz, 7.9 Hz), and 8.2 (1H, DD, J = 1.4 Hz, 7.9 Hz), 8,56 (4H, s), 11,18 (1H, s).

(60) 2-[4-Hydroxymethyl-3-(pyrrol-1-yl)benzoyl]-guanidine methanesulfonate

So pl. 131-133oC.

IR (nujol): 3340, 3120, 1707, 1590, 1190, 1040 cm-1< / BR>
NMR (DMSO-d6) 2,4 (3H, s), 4,47 (2H, s), 6,25 of 6.31 (2H, m), 7,05 - 7,11 (2H, m), 7,8 - 7,9 (2H, m), 8 (1H, d, J = 8.7 Hz), by 8.22 - 8,7 (4H, sh), 11,33 (1H, s).

Example 26.

According to the methods similar to the methods of examples 6, 17 and 18, the following compounds:

(1) 2-[2-Methoxy-5-(Pirro is -1
.

NMR (DMSO-d6) : to 2.42 (3H, s), 3,98 (3H, s), 6,25 to 6.3 (2H, m), 7,31 - 7,39 (3H, m), 7,8 - 7,89 (2H, m), 8,65 (4H, s) to 11.11 (1H, s).

Elemental analysis for C13H14N4O2CH4O3S:

Calculated: C 47,45, H 5,12, N 15,81

Found: C 47,09, H 5,16, N 15,52

(2) 2-[5-(Pyrrol-1-yl)-3-sulfamoylbenzoyl]guanidine methanesulfonate

So pl. 240-241oC.

IR (nujol): 3300, 3150, 1718, 1695, 1585, 1335, 1165 cm-1.

NMR (DMSO-d6) : 2,43 (3H, s), 6,37 - to 6.43 (2H, m), 7,51 - 7,56 (2H, m), the 7.65 (2H, s), 8,16 (1H, s), 8,25 - 8,31 (2H, m), 8,31 was 8.8 (4H, m), 11,64 (1H, s).

Elemental analysis for C12H13N5O3SCH4O3S:

Calculated: C 38,70, H 4,25, N 17,36

Found: C 38,45, H 4,25, N 17,08

(3) 2-[4-Methoxy-3-(pyrrol-1-yl)benzoyl]guanidine methanesulfonate

So pl. 220-221oC.

IR (nujol): 3320, 3100, 1705, 1605, 1260, 1048 cm-1.

NMR (DMSO-d6) : of 2.38 (3H, s), of 3.94 (3H, s), 6.22 per 6,28 (2H, m), 7,09 - to 7.15 (2H, m), 7,44 (1h, d, J = 8.7 Hz), to $ 7.91 (1H, d, J = 2.2 Hz), of 7.97 (1H, DD, J = 2.2 Hz, 8.7 Hz), scored 8.38 (4H, s), 11,19 (1H, s).

(+) APCI MACC (m/z): 259 /M free base + H/+.

Elemental analysis for C13H14N4O2CH4O3S:

Calculated: C 47,45, H 5,12, N 15,81

Found: C 47,30, H 5,17, N 15,72

(4) 2-[4-Acetamidomethyl-3-(pyrrol-1-yl)LASS="ptx2">

NMR (DMSO-d6) : 1,89 (3H, s), is 2.37 (3H, s), 4.2V (2H, d, J = 5.7 Hz), 6,26 - 6,34 (2H, m), 7.03 is for 7.12 (2H, m), to 7.61 (1H, d, J = 8,2 Hz), the 7.85 (1H, s), of 7.97 (1H, d, J = 8,2 Hz), 8,19 - 8,65 (5H, m), and 11.3 (1H, s).

(+) APCI MACC (m/z): 300 /M free base + H/+.

Elemental analysis for C15H17N5O2CH4O3S:

Calculated: C 48,60, H 5,35, N 17,71

Found: C 48,79 H 5,41, N 17,39

(5) 2-[3-(3-Cyano-1,5-dimethylpyrrole-2-yl)benzoyl] guanidine methanesulfonate

So pl. 230-132oC.

IR (nujol): 3330, 3080, 2220, 1700, 1650, 1600, 1170, 1050 cm-1.

NMR (DMSO-d6) : of 2.27 (3H, s), of 2.34 (3H, s), 3,49 (3H, s) of 6.4 (1H, s), 7,72 - 7,88 (2H, m), 7,95 - 8,08 (2H, m), 8,35 (4H, s), made 11.32 (1H, s).

(+) APCI MACC (m/z): 282 /M free base + H/+.

Elemental analysis for C15H15N5OCH4O3S:

Calculated: C 50,92, H 5,07, N 18,56

Found: C 50,85, H 5,02, N 18,36

(6) 2-[3-Hydroxymethyl-5-(pyrrol-1-yl)benzoyl]guanidine of izational

So pl. 154-156oC.

IR (nujol): 3350, 1700, 1590 cm-1.

NMR (DMSO-d6) : by 2.73 (2H, t, J = 7 Hz), to 3.67 (2H, t, J = 7 Hz), of 4.66 (2H, s), 6,3 - 6,4 (2H, m), between 7.4 to 7.5 (2H, m), 7,7 - 8 (3H, m), 8,44 (4H, sh. C) 11,38 (1H, s).

(+) APCI MACC (m/z): 259 /M free base + H/+.

Elemental analysis for C13H14N4O2C2-(pyrrol-1-yl)benzoyl]-guanidine methanesulfonate

So pl. 224-226oC.

IR (Nicol): 3350, 3170, 1700, 1645, 1590 cm-1.

NMR (DMSO-d6) : to 2.42 (3H, s), 6,3 - 6,4 (2H, m), and 7.5 and 7.6 (2H, m), 8 and 8.1 (3H, m), 8,31 (1H, s), 8,42 (4H, sh.C) 11,51 (1H, s), 11,64 (1H, s).

(+) APCI MACC (m/z): 272 /M free base + H/+.

Elemental analysis for C13H13N5O2CH4O3S:

Calculated: C 45,77, H 6,66, N 19,06

Found: C 45,69, H 4,75, N 18,87

(8) 2-[2-Nitro-5-(pyrrol-1-)benzoyl]guanidine hydrochloride

So pl. 253-254oC.

IR (nujol): 3350, 3120, 1720, 1690, 1620, 1590, 1570, 1330 cm-1.

NMR (DMSO-d6) : 6,38-6,44 (2H, m), 7,65-7,71 (2H, m), of 8.06 (1 H, DD, J= 2,5 Hz, 9 Hz), 8,21 (1H, d, J=2.5 Hz), 8,31 (1H, d, J=9 Hz), to 8.45 (2H, s), a total of 8.74 (2H, s), 12,77 (1H, s).

(+) APCl MASS (m/z): 274 /M free base + H/+.

Elemental analysis for C12H11N5O3HCl

Calculated: C 46,54, H 3,91, N 22,61

Found: C 46,24, H 3,90, N 22,27

(9) 2-[3-[2-((Z)-1-hydroxyimino)pyrrol-1-yl] benzoyl] - guanidine hydrochloride

So pl. 184-186oC.

IR (nujol): 3300, 1685 cm-1.

NMR (DMSO-d6) : of 2.26 (3H, s), 6,9-to 6.95 (1H, m), 7,65-to 7.77 (2H, m), 7,97-8,07 (2H, m), at 8.36 (1H, s), 8,51 (1H, s), 8,65 (2H, s), 8,86 (2H, s), 12,46 (1H, s).

(+) APCl MASS (m/z): 286/M free base +H/+.

(10) 2-[4-(2-Hydroxic, 1600 cm-1.

NMR (DMSO-d6) : of 3.75 (2H, t, J=4,7 Hz), 4,24 (2H, t), J=4,7 Hz), 6,2-of 6.26 (2H, m), 7,33-7,39 (2H, m), 7,42 (1H, d, J=8,8 Hz), with 8.05 (1H, DD, J=2.3 Hz, 8,8 Hz) to 8.12 (1H, d, J=2.3 Hz), 8,51 (2H, s), 8,72 (2H, s), 12,06 (1H, s).

(+) APCl MACC (m/z): 289/M free base + H/+.

(11) 8-(Diaminomethylene)-1-dimethylaminomethyl-4,4 - dimethyl-4H-pyrrolo/2,1-C//1,4/benzoxazin the dihydrochloride

So pl. 212-213oC.

IR (nujol): 3320, 1703, 1616 cm-1.

NMR (DMSO-d6) : was 1.58 (6H, s), and 2.8 (3H, s), 2,82 (3H, s), 4,88 (2H, sh. C) of 6.29 (1H, d, J=3,7 Hz), 6,7 (1H, d, J= 3,7 Hz), 7,31 (1H, d, J=8.5 Hz), 8,02 (1h, D, J=8.5 Hz), of 8.28 (1H, s), 8,65 (2H, s), 8,84 (2H, c), 10,22 (1H, s). 12, 31 (1H, s).

(+) APCl MASS (m/z): 342 /M free base + H/+.

(12) 2-[4-(Pyrrol-1-yl)benzoyl]guanidine hydrochloride

So pl. 267-268oC.

IR (nujol): 3350, 3130, 1685, 1600 cm-1.

NMR (DMSO-d6) 6,32-6,38 (2H, m), 7,56 and 7.36 (2H, m), a 7.85 (2H, d, J=8,8 Hz), 8,29 (2H, d, J=8,8 Hz), 8,63 (2H, s), cent to 8.85 (2H, s), 12,15 (1H, s).

(+) APCI MASS (m/z): 229 /M free base + H/+.

(13) 2-[3-[(Pyrrol-1-yl)methyl]benzoyl]guanidine hydrochloride

So pl. 210-212oC.

IR (nujol): 3340, 3240, 3120, 1695, 1630, 1570 cm-1.

NMR (DMSO-d6) : 5,19 (2H, s), 6-6,1 (2H, m), 6,84-6,93 (2H, m), 7,45-to 7.61 (2H, m), to 7.99 (1H, s), and 8.1 (1H, d, J=7,6 Hz), to 8.57 (2H, c) is I C13H14N4O HCl

Calculated: C 56,02, H, 5,42, N 20,10

Found: C 56,31, H 5.43, N 20,01

(14) 2-[3-(Pyrazole-3-yl)benzoyl]guanidine hydrochloride

So pl. 258-260oC.

IR (nujol): 3380, 3150, 1680, 1630 cm-1.

NMR (DMSO-d6) : 7,05 (1H, d, J=2.3 Hz), to 7.64 (1H, DD, J=7.8 Hz), 7,83 (1H, d, J=2.3 Hz), 8,08 (1H, d, J=7.8 Hz), 8,18 (1H, d, J=7.8 Hz), 8,67 (3H, s), 8,9 (2H, s), 12,23 (1H, s).

(+) APCl MACC (m/z) : 230 /M free base + H/+.

(15) 2-[3-(pyrimidine-4-yl)benzoyl]guanidine hydrochloride

So pl. 285-286oC (decomp.).

IR (nujol): 3270, 3050, 1710, 1575 cm-1.

NMR (DMSO-d6) : 7,8 (1H, DD, J=8 Hz, 8 Hz), 8,31 (1H, d, J=8 Hz), 8,42 (1H, d, J= 5.4 Hz), to 8.57 (1H, d, J=8 Hz), 8,66 (2H, s), 8,84 (2H, s), 8,96 (1H, d, J=5.4 Hz), 8,98-of 9.02 (1H, m), 9.3 to a 9.35 (1H, m), 12,37 (1H, s).

Elemental analysis for C12H11N5O HCl

Calculated: C better than anticipated at 51.90, H 4,36, N 25,22

Found: C 51,94, H 4,35, N ARE 24.88

(+) APCI MACC (m/z): 242 /M free base + H/+.

(16) 2-[3-(Pyridin-2-yl)benzoyl]guanidine the dihydrochloride

So pl. 257-258oC.

IR (nujol): 3400-3100 (W.), 1685, 1620 cm-1.

NMR (DMSO-d6) : 7,7-7,87 (2H, m), 8,27 is 8.38 (2H, m), 8,43-8,58 (2H, m), 8,76-8,94 (6H, m), 12,56 (1H, s).

(+) APCl MACC (m/z): 241 /M free base + H/+.

(17) 2-[3-(Pyridin-3-yl)benzoyl]guamr (DMSO-d6) : 7,8 (1H, DD, J=7.8 Hz), 8,06-8,17 (1H, m), 8,18 to 8.3 (2H, m), 8,65-9 (6H, m), 9,03-9,12 (1H, m), 9,46-9,52 (1H, m). 12,66 (1H, s).

Elemental analysis for C13H12N4O 2HCl

Calculated: C 49,86, H 4,51, N 17,89

Found: C 49,77, H of 4.54, N 18,19

(18) 2-[3-(5-Aminopyrazole-1-yl)benzoyl]guanidine the dihydrochloride

So pl. 248-250o.

IR (nujol): 3400, 3270, 3150, 2700, 1705, 1685, 1625 cm-1.

NMR (DMSO-d6) : 5,74 (1H, d, J=2.4 Hz), 7,71-to 7.84 (2H, m), of 7.96 (1H, d, J=7.9 Hz), compared to 8.26 (1H, d, and 17.9 Hz), a 8.34 (1H, s), 8,82 (4H, s). 12,47 (1H, s).

(+) APCl MACC (m/z): 245 /M free base + H/+.

Elemental analysis for C11H12N6O 2HCl

Calculated: C 41,66, H 4,13, N 26,50

Found: C 41,69, H 4,53, N 26,21

(19) 2-[2-(Pyrrol-1-yl)isonicotinoyl]guanidine hydrochloride

So pl. 255-256oC (decomp.)

IR (nujol): 3350, 3120, 1700, 1620, 1560 cm-1.

NMR (DMSO-d6) : 6,33-to 6.39 (2H, m), 7,76 (1H, DD, J=1.3 Hz, 5.2 Hz), 7,83-7,89 (2H, m), 8,54 (1H, J=1.3 Hz), 8.6 out of 8.95 (4H, m), 8,67 (1H, d, J=5,2 Hz). 12,63 (1H, s).

(+) APCl MACC (m/z): 230 /M free base + H/+.

Elemental analysis for C11H11N5O HCl

Calculated: C 49,73, H 4,55, N 26,36

Found: C 49,73, H 4,56, N 26,07

(20) 2-[[4-(Pyrrol-1-yl)pyridin-2-yl]carbonyl]guanidine hydrochloride

So pl. 257-258o.

IR (nujol):). is 8.75 (1H, d, J=5.6 Hz), 8,76 (2H, s), 8,84 (2H, s), 11,77 (1H, s).

(21) 2-[3-(2-Cyanoprop-1-yl)benzoyl]guanidine of izational

So pl. 149-150oC.

IR (nujol): 3320, 2220, 1717, 1585, 1172, 1033 cm-1.

NMR (DMSO-d6) : of 2.66 (2H, t, J=6.9 Hz), to 3.64 (2H, t, J=6.9 Hz), 6.48 in-6,55 (1H, m), 7,27-7,33 (1H, m), 7,63-to 7.68 (1H, m), to 7.84 (1H, DD, J=8 Hz, 8 Hz), 7,92-7,8 (1H, m), 8,01-of 8.09 (2H, m), scored 8.38 (4H, s). of 11.4 (1H, s).

Example 27.

The reaction of the methyl ester of 3-[[N-(2-hydroxyethyl)-N-benzyloxycarbonylamino] methyl]-5-(pyrrol-1-yl)benzoic acid hydrochloride guanidine according to the methods similar to the methods of examples 1, 3, 8, 10, 14 and 24 received the following connection:

2-[3-[(2-Oxoacridine-3-yl)methyl-5-(pyrrol-1-yl)- benzoyl] guanidine methanesulfonate.

So pl. 162-163oC.

IR (nujol): 3350, 3150, 1730, 1700, 1600 cm-1.

NMR (DMSO-d6) : of 2.44 (3H, s), 3,5-3,6 (2H, m), a 4.3 and 4.4 (2H, m), and 4.5 (2H, s), 6,3-6,4 (2H, m), and 7.5 and 7.6 (2H, m), 7,69 (1H, s), a 7.85 (1H, s), 8,02 (1H, s), of 8.47 (4H, sh.C). of 11.5 (1H, s).

(+) APCl MACC (m/z): 328 /M free base + H/+.

Elemental analysis for C16H17N5O3CH4O3S:

Calculated: C 48,22, H, 5,0, N 16,54

Found: C 48,40, H 5,1, N 16,44

Example 28.

By the method similar to the method of example 12, the following compound is (nujol): 3300, 1650, 1577 cm-1.

NMR (DMSO-d6) : 6-6,5 (8H, sh), 6,11-of 6.17 (2H, m), 6,93-6,99 (2H, m), 7,44 (1H, d, J=7,6 Hz), 7,9-to 7.99 (2H, m).

Example 29.

By the method similar to the method of example 20, the following connection:

2-[4-(Diaminomethylene)-2-(pyrrol-1-yl)- benzoyl] guanidine dimethanesulfonate.

So pl. 276-278oC.

IR (nujol): 3350, 3110, 1725, 1710, 1660, 1605, 1250, 1405 cm-1.

NMR (DMSO-d6) : a 2.36 (6H, s), 6,28-6,34 (2H, m),? 7.04 baby mortality, and 7.1 (2H, m), 7,87-8,07 (3H, m), 8.07-a 8,75 (8H, m), 11,53 (1H, s), up 11,86 (1H, s).

(+) APCI MACC (m/z): 314 /M free base + H/+.

Elemental analysis for C14H15N7O22CH4O3S:

Calculated: C 38,02, H 4,59, N 19,40

Found: C 37,79, H 4,40, N 19,06

Example 30.

By the method similar to the procedures of examples 12 and 20, we obtained the following compounds:

(1) 2-[5-(2-Cyanophenyl)-3-(diaminomethylene)- benzoyl] guanidine dimethanesulfonate

So pl. 270-271oC.

IR (nujol): 3350, 1720, 1205, 1050 cm-1.

NMR (DMSO-d6) : to 2.42 (6H, s), with 7.6 and 8.1 (4H, m), 8,44 (2H, s), 8,59 (1H, s), 8-8,7 (4H, sh), 11,64 (1H, sh).

(+) APCI MACC (m/z): 350 /M free base + H/+.

Elemental analysis for C17H15N7O22CHOnyl)-5-phenylbenzyl] - guanidine dimethanesulfonate

So pl. 265-266oC.

IR (nujol): 3350, 1720, 1205, 1040 cm-1.

NMR (DMSO-d6) : of 2.45 (6H, s), 7,45 to 7.7 (3H, m), a 7.85-to 7.93 (2H, m), and 8.4 to 8.8 (11H, m), 11,66 (2H, s).

(+) APCI MACC (m/z): 325 /M free base + H/+.

Elemental analysis for C16H16N6O2C2H8S2O6< / BR>
Calculated: C 41,85, H 4,68, N 16,27

Found: C 41,69, H 4,76, N 15,93

(3) 2-[3-(3-Diaminotrinitrobenzene)-benzoyl] -guanidine dimethanesulfonate

So pl. > 300oC.

IR (nujol): 3350, 3100, 1710, 1580, 1270, 1040 cm-1.

NMR (DMSO-d6) : a 2.36 (6H, s), 7,88 (2H, DD, J = 7.8 Hz, 7.8 Hz), 8 (2H, d, J = 7.8 Hz), 8,13 (2H, d, J = 7.8 Hz), of 8.27 (2H, s), and 8.4 (8H, sh.C.), 11,41 (2H, s).

(+) APCI MACC (m/z): 325 /M free base + H/+.

Example 31.

To the mixture 2-[3-[2-(((E)-2-carboxyethyl)pyrrol-1-yl] benzoyl]- guanidine (0.25 g), tetrahydrofuran (5 ml) and methanol (5 ml) is added 2 M solution of (trimethylsilyl)diazomethane in hexane (0,84 ml) and the mixture is stirred for 25 minutes at room temperature. To the reaction mixture are added acetic acid (2 ml) and stirred for 5 minutes. Then to the resulting mixture are added ethyl acetate and water and adding 20% aqueous solution of potassium carbonate by ustanavlivaetsya residue from a mixture of ethanol with diisopropyl ether get 2-[3-[2-(((E)-2-methoxycarbonylethyl)pyrrol-1-yl]benzoyl]- guanidine (0.15 g).

So pl. 165-168oC (decomp.).

IR (nujol): 3270, 1690, 1620 cm-1.

NMR (DMSO-d6) : 3.6V (3H, s), 6-8,2 (4H, sh), x 6.15 (1H, d, J = 15.7 Hz), 6,34 is 6.4 (1H, m), 7,02-7,06 (1H, m), 7,21 (1H, d, J = 15.7 Hz), 7,25 (1H, s), 7,42-7,49 (1H, m), to 7.59 (1H, DD, J = 7,7 Hz, 7.7 Hz), 8,01 (1H, s), 8,15 (1H, d, J = 7.7 Hz).

(+) APCI MACC (m/z): 313 /M+H/+.

Elemental analysis for C16H16N4O3< / BR>
Calculated: C 61,53, H 5,16, N 17,94

Found: C 61,31, H 5,22, N 18,07

Example 32.

To a solution of 2-[4-benzyloxy-3-(pyrrol-1-yl)benzoyl] guanidine (1.9 g) in methanol (20 ml) and tetrahydrofuran (20 ml) is added 10% palladium on coal (0.2 g) and the mixture for 30 minutes, subjected to catalytic recovery at room temperature and atmospheric pressure. The catalyst is filtered off and the filtrate evaporated in vacuum. The residue is dissolved in methanol (15 ml) and to the solution was added with stirring methansulfonate acid (0.4 ml). Formed after adding to the solution of diisopropyl ether, the precipitate is filtered off. By recrystallization of the precipitate from a mixture of methanol with diisopropyl ether get methanesulfonate 2-[4-hydroxy-3-(pyrrol-1 - yl)benzoyl]guanidine.

So pl. 128-133oC.

IR (nujol): 3350, 3150, 1690, 1595, 1240, 1045 cm-1.

NMR (D Example 33.

To a solution of guanidine hydrochloride (63.7 g) in dry N,N-dimethylformamide (300 ml) was added a 28% solution of sodium methoxide in methanol (122,2 ml) and the mixture is stirred for 20 minutes at room temperature. After adding to the mixture of methyl ester of 3-(2-cyanoprop-1-yl)benzoic acid (30.5 g) the mixture is stirred for 2 hours at the same temperature. Then the reaction mixture under stirring transferred into the water. Filtration of the resulting precipitate receive 2-[3-(2-cyanoprop-1-yl)benzoyl]guanidine (21,66 g).

So pl. 136-138oC.

IR (nujol): 3390, 2220, 1637 cm-1.

NMR (DMSO-d6) : 6,3-6,4 (4H, sh), 6,46 (1H, DD, J = 2,8 Hz, 3.9 Hz), 7,24 (1H, DD, J = 1.6 Hz, 3.9 Hz), 7,56 (1H, DD, J = 1.6 Hz, 2.8 Hz), 7,58-of 7.69 (2H, m), 8,11-8,19 (2H, m).

Example 34.

To a mixture of 2-[3-(2-cyanoprop-1-yl)benzoyl]guanidine (2 g) and methanol (20 ml) is added methanesulfonyl acid (0.8 ml) and the mixture is stirred for 30 minutes at room temperature. After adding to the mixture of ethyl acetate (20 ml) the resulting precipitate is filtered off. By recrystallization of the precipitate from the water get methanesulfonate 2-[3-(2-cyanoprop-1-yl)benzoyl] guanidine (1.48 g).

So pl. 200-201oC.

IR (nujol): 3350, 3100, 2220, 1720, 1585, 1165, 1045 cm-1.

NMR (DMSO-d6) : 2,36 (32">

Elemental analysis for C13H11N5O CH4O3S:

Calculated: C 48,13, H 4,33, N 20,05

Found: C 48,16, H is 4.21, N 19,83

Appendix A. Inhibition of Na+/H+-exchange of Ki (M) of 2.51 10-8.

< / BR>
(Example 9-17)

Appendix B, see the end of the description.

Appendix C.

Methods

Measurement of the activity of Na+/H+- metabolism in rat lymphocytes.

Activation of Na+/H+metabolism in rat lymphocytes by the method of Grinstein et al. (1989). Rats-males Sprague-dauli (8-9 weeks) killed and removed the thymus and kept in the environment of NaCl, containing 140 mm NaCl, 1 mm KCl, 1 mm CaCl2, 1 mm MgCl2, 10 mm glucose, 20 mm Hepes buffer (pH 7.3) at room temperature. Then the thymus sharp scissors, cut into small pieces, was diluted in 20 ml of medium NaCl and transferred to a homogenizer (Dounce type, equipped with netpo fixed pestle. Cells were separated using 10 soft bumps. To remove large cellular konglomerat and connective tissue, the resulting suspension was filtered through 12 layers of surgical gauze and then the filtrate was centrifuged at 1000 g for 10 minutes. The precipitate is re-suspended in 20 ml of medium NaCl and again besieged, as described previously. The final osado the P>-exchange was determined by measuring the increase in cell volume induced intracellular acidification. The reaction was started by introducing 0.1 lymphocytes prepared as described above, in 20 ml of Na-propionic buffer containing 140 mm Na-propionate, 1 mm KCl, 1 mm CaCl2, 1 mm MgCl2, 10 mm glucose, 20 mm Hepes buffer (pH of 6.7). Quantitative distribution of the cell population was determined on a Coulter counter model TAII (Multi-channel particle counter, Coulter Electronics Inc.) equipped with a 50 μm aperture. The average diameter of the cells was determined through 0,5, 1, 1,26, 2, 3, 4, 5 minutes at room temperature. Then calculate the volume of cells and determined the initial rate of increase at the expense of Na+/H+-exchange. Based on the values of these velocities evaluated the inhibitory effect of the drug and expressed in the value of Ki.

Arrhythmias induced by ischemia and recovered by perfusion.

For this experience used Crome et al. (1986) modification. Rats male SD (aged 9-10 weeks) were euthanized using pentobarbital sodium (50 mg/kg, intraperitoneally), was intubated and perform pulmonary ventilation indoor air shock volume of 4.5 ml with a frequency of 50 beats. ECG was recorded with a lead electrode. Fiziologicheskii 5 minutes in order to avoid clogging. Performed thoracotomy for applying ligatures to the coronary artery on the left side of the chest above the heart, and carried out a corking beginning of the left anterior descending coronary artery by applying pressure during aspiration, which guarantees the emergence of regional ischemia. Successful completion of the occlusion was confirmed by ECG changes induced by ischemia. After 5 minutes of ischemia, spent restoring perfusion stop aspiration and determined the frequency of manifestations of ventricular tachycardia and ventricular fibrillation, with a duration of more than 5 seconds.

The determination of the size of myocardial infarction.

The size of infarction was determined by the method Bernaner (1985). Thoracotomy for applying ligatures to the coronary artery was performed as described above. Rats were injected two drip intravenous injection of physiological solution and the test substance for 5 minutes before applying ligatures and 5 minutes to restore perfusion. The left anterior descending coronary artery left the ligature about 2-3 mm from its beginning. Successful completion of the occlusion was confirmed by the typical rise-wave on electrocardiogram ST. After 60 minutes of ischemia, which smenila and cut into 6 slices about 5 mm parallel to the arterio-venous furrow. Then all sections were stained by incubation in 0.5% triphenyltetrazolium chloride in buffered physiological solution (-) for 10 minutes at 37oC and fixed in 10% formalin. After 24 hours they were photographed with the help of computer planimetry program (Luzlx, Nickon) was determined infarction area (not painted TTC) and reinforcing region. The size of infarction was calculated as the sum of necrotic fields on 6 slices of a whole area (the amount of necrotic fields and fields without necrosis) and was expressed in percentage of the whole plot.

Statistics.

The results by the values of the size of myocardial infarction were expressed as the mean SEM, and comparative statistical processing was performed using Well-Wallis test, and identifying with this test, a statistically significant difference, the data were then analyzed using the test were analyzed using X2test. The level of P < 0,05 was considered significant.

1. Derivatives of guanidine of the formula I

< / BR>
where Y Is N or C - R1in which R1is hydrogen, (lower)alkyl, hydroxy, (lower)alkoxygroup, hydroxy(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkoxygroup, hydroxy (and 2 nitrogen atom;

R2represents hydrogen, aryl which may have one Deputy, selected from the group comprising halogen, nitro, cyano, (lower)alkyl, trihalogen(lower)alkyl, protected amino group; alloctype, trihalogen(lower)alkyl, acyl 5 - or 6-membered heterocyclic group with 1 to 4 heteroatoms, independently selected from the group comprising nitrogen, sulfur and oxygen, which may have a substituent(s) selected(s) from the group comprising carboxypropyl, secure carboxypropyl, acyl, (lower)alkyl, halogen, hydroxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, amino, protected amino, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, carboxy(lower)alkyl or heterocyclyl(lower)alkyl;

R3is hydrogen, (lower)alkoxygroup, the hydroxy-group, 5-membered heterocyclic group with the nitrogen atom as heteroatom, or

R2and R3connected to each other with the formation of 2-valent radical of the formula

< / BR>
in which R5is hydrogen or (lower)alkyl, R6is hydrogen or (lower)alkyl, R11is hydrogen or cyano;

Z is N or C - R4in which R4is hydrogen, halogen, cyano, hydroxy(lower)P>12in which R12is hydrogen,

or pharmaceutically acceptable salt of this compound.

2. Connection on p. 1, where Y Is N or C - R1in which R1is hydrogen, (lower)alkyl, hydroxy-group, (lower)alkoxygroup, hydroxy(lower)alkyl, acylamino(lower)alkyl, carboxy(lower)alkoxygroup, hydroxy(lower)alkoxygroup, phenyl, piperidyl or pyrrolyl; R2represents hydrogen, naphthyl or phenyl, each of which may have one Deputy, selected from the group comprising trihalogen(lower)alkyl, cyano, (lower)alkyl, halogen, the nitro-group and a protected amino group; fenoxaprop; trihalogen(lower)alkyl; aroyl; pyrrolyl, tetrazolyl, pyrazolyl, thienyl, furyl, thiazolyl, pyridyl or pyrimidinyl, each of which may have 1 to 3 substituent selected from the group comprising carboxypropyl, secure carboxypropyl, acyl, (lower)alkyl, halogen, hydroxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, amino, protected amino, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, carboxy(lower)alkyl or pyrrolyl(lower)alkyl; R3is hydrogen, (lower)alkoxygroup, the hydroxy-group, pyrrolyl or R2and R3soybean (lower)alkyl; R6is hydrogen or (lower)alkyl; R11is hydrogen or cyano;

Z is N or C - R4in which R4is hydrogen, halogen, hydroxy(lower)alkyl, cyano, pyrrolyl, tetrazolyl, carbarnoyl, which may have a Deputy selected from the group comprising diamino(lower)alkylidene, di(lower)alkylamino(lower)alkyl and heterocycle(lower)alkyl; W is N or C - R12in which R12- hydrogen.

3. Connection on p. 2, where Y Is N or C - R1in which R1is hydrogen, lower alkyl, hydroxy-group, the lowest alkoxygroup, hydroxy(lower)alkyl, (lower)alkanolamine(lower)alkyl, carboxy(lower)alkoxygroup, hydroxy(lower)alkoxygroup, phenyl, piperidyl or pyrrolyl; R2is hydrogen, phenyl; trihalogen(lower)alkylphenyl, cyanophenyl, (lower)alkylphenyl, halogenfree, nitrophenyl, trihalogen(lower)alkylsulfonamides, naphthyl, phenyloxy, trihalogen(lower)alkyl, benzoyl, pyrrolyl, tetrazolyl, pyrazolyl, thienyl, furyl, thiazolyl, pyridyl or pyrimidinyl, each of which may have 1 to 3 substituent selected from the group comprising carboxylate, lower alkanoyl, carbarnoyl, (lower)alkyl, halogen, hydroxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, langr and pyrrolyl(lower)alkyl; R3is hydrogen, (lower)alkoxygroup, the hydroxy-group or pyrrolyl or R2and R3connected to each other with the formation of 2-valent radical of the formula

< / BR>
in which R5is hydrogen or (lower)alkyl; R6is hydrogen or (lower)alkyl; R11is hydrogen or cyano;

Z is N or C - R4in which R4is hydrogen, halogen, cyano, hydroxy(lower)alkyl, pyrrolyl, tetrazolyl, diamino(lower)alkylaminocarbonyl, di(lower)alkylamino(lower)allylcarbamate or morpholinyl(lower)allylcarbamate.

4. Connection on p. 3, where Y Is N or C - R1in which R1is hydrogen, (lower)alkyl, hydroxy-group, (lower)alkoxygroup, hydroxy(lower)alkyl, (lower)alkanolamine(lower)alkyl, carboxy(lower)alkoxygroup, hydroxy(lower)alkoxygroup, phenyl, piperidyl or pyrrolyl; R2is hydrogen, phenyl; trihalogen(lower)alkylphenyl, cyanophenyl, (lower)alkylphenyl, halogenfree, nitrophenyl, trihalogen(lower)alkylsulfonamides, naphthyl, fenoxaprop, trihalogen(lower)alkyl, benzoyl, pyrrolyl, carboxypropyl, (lower)alcanoterreos, carbamoylethyl, mono(or di)-(lower)acylpyrrole, hydroxyimino(lower)acylpyrrole; (di(lower)alkyl is caniparoli, carboxy(lower)acylpyrrole, dialogerror, pyrrolyl, substituted (lower)alkyl and cyano, pyrrolyl, substituted di(lower)alkylamino(lower)alkyl and cyano, tetrazolyl, pyrazolyl, possibly substituted amino group, thienyl, possibly substituted by cyano, furyl, possibly substituted by cyano, thiazolyl, pyridyl; pyrimidinyl or pyrrolyl(lower)alkyl; R3is hydrogen, (lower)alkoxygroup, the hydroxy-group or pyrrolyl or R2and R3connected to each other with the formation of 2-valent radical of the formula

< / BR>
in which R5is hydrogen or (lower)alkyl; R6is hydrogen or (lower)alkyl; R11is hydrogen or cyano.

5. Connection on p. 4, where Y is C - R1where R1is hydrogen, R2is phenyl or cyanophenyl, R3is hydrogen, Z is C - R4where R4is hydrogen, and W - C - R12where R12- hydrogen.

6. Connection on p. 5, selected from the group comprising 2-(3-phenylbenzyl)guanidine or its hydrochloride and 2-[3-(2-cyanophenyl)benzoyl]guanidine or its hydrochloride.

7. Connection on p. 4, where Y is C - R1where R1is hydrogen, R2- pyrrolyl, cyanopropyl, hydroxyimino(lower)acylpyrrole, cantieni and cyanophenyl, R12in which R12- hydrogen.

8. Connection on p. 7, selected from the group including

2-[3-(pyrrol-1-yl)benzoyl] guanidine or its hydrochloride or methanesulfonate,

2-[3,5-di-(pyrrol-1-yl)benzoyl]guanidine,

2-[3-nitro-5-(pyrrol-1-yl)benzoyl]guanidine,

2[3-(2-morpholinoethyl)-5-(pyrrol-1-yl)benzoyl] guanidine or its dihydrochloride,

2-[3-(3-morpholinopropan)-5-(pyrrol-1-yl)benzoyl] guanidine or its dihydrochloride,

2-[3-hydroxymethyl-5-(pyrrol-1-yl)benzoyl] guanidine or its hydrochloride, methanesulfonate or isocyanate,

2-[3-(2-cyanoprop-1-yl)benzoyl] guanidine or its hydrochloride, polysulfate, fumarate, maleate, polycitra, methanesulfonate or isothionate,

2-[3-(2-cyanoprop-1-yl)-5-(diaminotrinitrobenzene)benzoyl] guanidine or its methanesulfonate,

2-[3-(Z)-2-gidroksiiminobetulonovoi-1-yl] benzoyl/guanidine or its hydrochloride,

2-[3-(2-cyanothiophene-3-yl)benzoyl]guanidine or its methanesulfonate and

2-[3-(2-cianfuran-3-yl)benzoyl]guanidine or its methanesulfonate,

2-[3-(2-dimethylaminoethyl)carbarnoyl]-5-(pyrrol-1-yl)benzoyl/guanidine.

9. Connection on p. 4, where Y is C - R1where R1- (W - C - R12where R12- hydrogen.

10. Connection on p. 9, selected from the group comprising 2-[4-n-butyl-3-(pyrrol-1-yl)benzoyl] guanidine or its hydrochloride and 2-[4-hydroxymethyl-3-(pyrrol-1-yl)benzoyl]guanidine or its methanesulfonate.

11. Connection on p. 4, where Y is C - R1where R1is hydrogen, R2and R3are connected to each other to form divalent radical of the formula

< / BR>
in which R5is hydrogen, R6is hydrogen and R11is hydrogen or cyano,

Z - C - R4where R4is hydrogen and W - C - R12where R12- hydrogen.

12. Connection on p. 11, selected from the group comprising 6-(diaminomethylene)-4H-pyrrolo(2,1-C) (1,4)benzoxazine or its methanesulfonate and 1-cyano-6-(diaminomethylene)-4H-pyrrolo(2,1-C)(1,4)benzoxazine or methanesulfonate.

13. The method of obtaining derivatives of guanidine of the formula /I/

< / BR>
where Y Is N or C - R1where R1is hydrogen, (lower)alkyl, hydroxy-group, (lower)alkoxygroup, hydroxy(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkoxygroup, hydroxy(lower)alkoxygroup, phenyl, 5 - or 6-membered heterocyclic group having as heteroatoms 1, or 2 atoms which includes halogen, nitro, cyano, (lower)alkyl, trihalogen(lower)alkyl and protected amino group, alloctype, trihalogen(lower)alkyl, acyl, 5 - or 6-membered heterocyclic group with 1 to 4 heteroatoms, independently selected from the group comprising nitrogen, sulfur and oxygen, which may have a substituent(s) selected(s) from the group comprising carboxypropyl, secure carboxypropyl, acyl, halogen, (lower)alkyl, hydroxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, amino, protected amino group, carocci(lower)alkenyl, protected carboxy(lower)alkenyl, carboxy(lower)alkyl or a heterocycle(lower)alkyl.

R3is hydrogen, (lower)alkoxygroup, the hydroxy-group, 5-membered heterocyclic group containing 1 nitrogen atom as heteroatom, or

R2and R3are connected to each other to form divalent radical of the formula

< / BR>
in which R5is hydrogen or (lower)alkyl, R6is hydrogen or (lower)alkyl, R11is hydrogen or cyano;

Z is N or C - R4where R4is hydrogen, halogen, hydroxy(lower)alkyl, cyano, 5-membered heterocyclic group with 1 to 4 nitrogen atoms as the heteroatoms, or acyl;

W is N or C - R123, Y, W and Z each accepts these values,

or its reactive on carboxylate derivative, or its salt with the compound of the formula

< / BR>
or its reactive on aminogroup derivative, or its salt.

14. The method of inhibition of Na+/H+- metabolism in the cells, characterized in that impose a derivative of guanidine according to p. 1 or its pharmaceutically acceptable salt to a person or animal.

15. The method according to p. 14, characterized in that a derivative of guanidine according to p. 1 or its pharmaceutically acceptable salt is used for the treatment of myocardial infarction and ischemic arrhythmias.

Priority points and features:

17.05.93 on PP.1 - 5, 7, 9 and 13, where R2is hydrogen, aryl, alloctype, 5 - or 6-membered heterocyclic group with 1 to 4 heteroatoms, independently selected from the group comprising nitrogen, sulfur and oxygen, which may have a substituent(s) selected(s) from the group comprising carboxypropyl, secure carboxypropyl, acyl, (lower)alkyl, halogen, hydroxyimino(lower)alkyl, di(lower)alkylamino(lower)alkyl, cyano, amino, protected amino, carboxy(lower)alkenyl, protected carboxy(lower)alkenyl, carboxy(lower)allievate or R2and R3connected to each other with the formation of 2-valent radical of the formula

< / BR>
in which R5- (lower)alkyl, R6- (lower)alkyl, R11is hydrogen;

Z is N or C - R4in which R4is hydrogen, halogen, a 5-membered heterocyclic group with 1 to 4 nitrogen atoms as heteroatoms, acyl.

10.12.93 on PP. 1 to 5, 7 and 13, where R2is aryl which may have one Deputy, selected from the group comprising halogen, nitro, cyano, (lower)alkyl, trihalogen(lower)alkyl, protected amino group; Z is C - R4in which R4is cyano or hydroxy(lower)alkyl - 10.12.93; p. 8, wherein the compound of formula I is selected from the group comprising 2-(3-)pyrrol-1-yl(benzoyl)-guanidine or its hydrochloride or methanesulfonate, 2-[3-hydroxymethyl-5-(pyrrol-1-yl)benzoyl]guanidine or its hydrochloride or methanesulfonate, 2-[3-(2-cyanoprop-1-yl)benzoyl] guanidine or its hydrochloride or methanesulfonate.

 

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< / BR>
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