UA51621C2 - Derivatives of 3-amino-2-mercaptobenzoic acid and method of their producing - Google Patents

Abstract

Compounds of the formula I and disulfides thereof and salts thereof are important intermediate products for the preparation of compounds having a microbicidal and plant-immunizing action, of the formula III In the compounds of the formulae I and III: X is halogen, n is 0, 1, 2 or 3; Z is CN, CO-A or CS-A, A is hydrogen, halogen, OR1, SR2 and N(R3)R4; R1 to R4 are hydrogen, a substituted or unsubstituted, open-chain, saturated or unsaturated hydrocarbon radical containing not more than 8 carbon atoms, a substituted or unsubstituted cyclic, saturated or unsaturated hydrocarbon radical containing not more than 10 carbon atoms, substituted or unsubstituted benzyl or phenethyl, a substituted or unsubstituted alkanoyl group containing not more than 8 carbon atoms, a substituted or unsubstituted benzoyl group or a substituted or unsubstituted heterocyclyl radical; or R3 and R4, together with the nitrogen atom to which they are bonded, are a 5- or 6-membered, substituted or unsubstituted heterocyclic radical having 1-3 heteroatoms 0, S and/or N. Processes for the preparation of compounds of the formula I are described.

Description

Description of the invention

The present invention relates to the compound of formula 7! 5H (Op 170 Mn, to its disulfide and to its salts, Kk to the methods of its preparation and application in the preparation of compounds of formulas II, possessing microbicidal action and the ability to immunize plants 15 7 PI 5 - zm and

M

20

In the compounds of the formulas and and HER

X denotes fluorine, n denotes 0, 1, 2 or 3; 7 denotes CM, СО-А or С5-А, and 25А denotes hydrogen, OKU, ZK» or M(К3)Ка; at

K.-Ki denote hydrogen, a substituted or unsubstituted, saturated or unsaturated hydrocarbon radical with an open chain containing no more than 8 carbon atoms, a substituted or unsubstituted cyclic saturated or unsaturated hydrocarbon radical containing no more than carbon atoms, substituted or unsubstituted benzyl or phenethyl, a substituted or unsubstituted alkanoyl group containing no more than 8 carbon atoms, a substituted or unsubstituted benzoyl group, or a substituted or unsubstituted heterocyclic radical; or Kz and K; together with the nitrogen atom to which they are connected, denote 5- or b- member substituted or unsubstituted ise) heterocyclic radical containing 1 - C heteroatom O, 5 and/or M; except for a compound in which n "- denotes 0 and 7 denotes CM or СОМН" or СОН.

Combinations of formulas! include at least one basic group and can, thus, t) form acid-addition salts. They are obtained, for example, by reacting with mineral acids, in particular with sulfuric acid, phosphoric acid or hydrohalic acid, with organic carboxylic acids, in particular with acetic acid or oxalic, malonic, maleic, fumaric or phthalic acid, with hydroxycarboxylic acids, in in particular with ascorbic, lactic, malic, tartaric or citric acid, with benzoic acid, or with organic - with sulfonic acids, in particular with methane- or p-toluenesulfonic acid. When the substituent 7 has a ZH-group "» or an acid group, compounds of the formulas potassium and magnesium salts, and salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, mono-, di- and tri(lower alkyl)amine, in particular zyl, distyl-, tristyl- and dimethylpropylamine, mono- , di- and trihydroxy(lower - alkyl)amine, in particular mono-, di- and trisethanolamine. Moreover, under certain conditions, it is possible to obtain the corresponding internal salts.

If not specified otherwise, the general concepts used above and below have the following meanings. with 50 Hydrocarbon radical! they can be saturated or unsaturated, open-chain or cyclic, they are a mixture of open-chain and cyclic radicals, for example, cyclopropylmethyl or benzyl.

Depending on the number of carbon atoms, alkyl groups are considered straight-chain or branched and are, for example, methyl, ztyl, n-propyl, isopropyl, n-butyl, sec-butyl, h-isobutyl, tert-butyl, sec-amyl, tert-amyl , 1-hexyl and 3-hexyl.

Gee! Alkenyl, alkynyl and alkenynyl groups are unsaturated hydrocarbon radicals! at least with 3-fold bonds, for example, butadienyl, hexatrienyl, 2-penten-4-ynyl. o The term "alkenyl" refers to straight-chain or branched alkenyl, in particular allyl, methallyl, 1-methylvinyl or but-2-en-1-yl. Preferred! alkenyl radical, the chain of which contains C 60 - 4 carbon atoms.

Similarly, depending on the number of carbon atoms, alkynyl can be straight-chain or branched, for example, propargyl, but-1-yn-1-yl, and but-1-yn-3-yl. Propargyl is preferred.

Cyclic unsaturated hydrocarbon radical! they can be aromatic, for example, phenyl and naphthyl, or non-aromatic, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctadienyl, or partially aromatic, for example, tetrahydronaphthyl and indanyl.

Halogen is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

Haloalkyls can contain the same or different atoms! halogen, for example, fluoromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoromethyl, 2-fluoromethyl, 2-chloromethyl, 2,2,2-trichloromethyl and 3,3,3-trifluoropropyl.

Alkoxy groups can be named, for example, methoxy-, ztoxy-, propyloxy-, isopropyloxy-, n-butyloxy-, isobutyloxy-, sec-butyloxy and tert-butyloxy groups. Preferred methoxy- (and toxygroups!.

Haloalkyl groups! are, for example, difluoromethoxy-, trifluoromethoxy-, 2,2,2-trifluoroethoxy-, 1,1,2,2-tetrafluoroethoxy-, 2-fluoroethoxy-, 2-chloroethoxy- and 2,2-difluoroethoxy groups! 70 Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

Alkanoyl is either straight-chain or branched. Examples of Ego include formyl, acetyl, propionyl, butyryl, pivaloyl or octanoyl.

The term "heterocyclic radical" refers to 05- or b-membered aromatic and non-aromatic rings with heteroatoms M, O and/or 5. In addition, an unsubstituted or substituted benzo group can be condensed with such a heterocyclic radical, /5 bonding with the rest of the molecules . Examples of heterocyclic groups are pyridyl, pyrimidinyl, imidazolyl, thiazolyl, 1,3,4-thiadiazolyl, triazolyl, thienyl, furanyl, pyrrolyl, morpholinyl, oxazolyl and corresponding partially or fully hydrogenated rings. Examples of heterocyclic groups with condensed benzo groups are quinolyl, isoquinolyl, benzoxazolyl, quinoxalinyl, benzothiazolyl, benzimidazolyl, indolyl, and indolinyl.

Compounds of formulas I, possessing a bactericidal effect and the ability to immunize plants, and the method! their preparation is known, for example, from the European patent 313512. The method described in it is unacceptable! for industrial production, as they include many reaction stages, some of which are difficult to implement, resulting in an overall unsatisfactory product output.

For this reason, there is a need to develop a new, industrially more advanced i) method of synthesis of such compounds.

Combinations of formulas | in accordance with the invention, they provide a new opportunity to obtain compounds of the formulas! It is as shown in scheme 1. Such a synthesis is characterized by the easy availability of the precursor, the use of common reagents and a good yield of the product even in the case when the intermediate product is not isolated. In addition to the above, the present invention relates to this synthesis. with

In the formulas in the scheme 1X, n and 7 have the meanings specified for the formulas I!, and T denotes hydrogen, He

C.-Cioalkyl, in particular C.sub.1-C.sub.alkyl, C.sub.3-S.sub.alkyl, C.sub.3-S.sub.alkyl, C.sub.3-S.sub.cycloalkyl or substituted or unsubstituted phenyl, benzyl or phenethyl. --

Precursors of formula M are compounds that can be obtained industrially or can be obtained by known methods, for example, by reducing the corresponding nitro compounds.

Scheme I « 7 7 - s and more

B in Mn, MN MN

M y 2 oo en ry Mn--T (Op »

Fu m Va, sh with 50 Ii M -x Ge | s» dream 7 vn same V, i

F! MN, Mn,

Ia 1 name) sorrno (s) Y (vv) 60 soOon 7 5 5

EK ho es tk y y

M M

65 Sha SHI

More specifically, this reaction stage can be carried out as follows.

(17 5SM-T/for example, methyl isothiocyanate /inert solvent/ under appropriate conditions in the presence of an acid! or a base; or ZSM-salt. (2) An oxidizing agent, for example, 505Si", HgO, NiZO,/ bromide or Si". (3 ) Aqueous strong base, for example, potassium hydroxide solution, preferably in an inert atmosphere.

Reactions (1), (2) and (3) as described), for example, in Ogo. Bupipeviv, SoiYi., volume I, p. 7b; 9. Her.

Spega., volume 17, page 1325 (1980); in US patent 5374737; in the Ukrainian Chemical Journal, volume 22, 363, 1956, on which there is a link in Snega. Abrzeg 22, 43585 (1957). 70 (For) Diazotization / NzZRO" (Zupii. Sogat., vol. 10, p. 167, 1980). (4) Diazotization with cyclization, for example, with nitric acid (NOMO), inorganic or organic nitrite, in particular sodium nitrite or isoamyl nitrite (see, for example, European patent 313512). (4a) For example, hydrazine/ztanol, basic hydrolysis or similar to what is indicated in 4) (Supp. Sott.,

This is 10, p. 167, 1980). (45) For example, 2p/acid, Re/acid (Neegosusiis Sotrotspav, volume 7, p.541 and further) or Na/catalyst. (5) Conversion of the COOH group into group 7, where 7 has the meaning specified for formula I, can be carried out by known methods, as shown in scheme 3.

Preferable combinations of formulas! And the following are recognized. (1) Compounds in which 7 denotes CM, СО-А or С5-А,

A denotes OKU, ZK" or M(Kz)Ka, and in which

Ku, Ko and Kz denote hydrogen, C--C alkyl, which is unsubstituted or substituted by 1-5 halogen atoms,

C3-Svcycloalkyl, C.i-C; alkokoy-, phenoxy-, benzyloxy-, C--C; acyloxy-, benzoyloxy group, hydroxyl, sch ov nitro-, cyano group, C.-C; canoyl, benzoyl, carboxyl, C .-C, alkoxycarbonyl, benzyloxycarbonyl, amino-, C-C-C alkylamino-, C--C dialkyl-amino group or heterocyclyl, and)

C3-Svalkenyl, which is unsubstituted or substituted by 1-5 halogen atoms, C3-Svalkynyl, C3-Svcycloalkyl,

S.-C.alkanoyl, phenyl, benzyl or phenethyl, phenyl ring of which are not substituted! or contain from one to three substituents from the group of hydroxyl halogen, C-Salalkyl, haloC. or substitution by one or three identical or different substituents from the groups! halogen, C 4-Soalkyl, halomethyl or nitro groups; "at

Ku; denotes hydrogen, C1-C6alkyl, substituted or benzyl; or Kz and K); together with the nitrogen atom with which they are connected, they represent a 5- or b-membered ring with 1-2 heteroatoms 0, 5 and/or M, where - from 5 the rings are unsubstituted or contain one or two identical or different substituents from groups uu halogen, C-Salkyl or C-Socoxycarbonyl. (2) Connections in which

X denotes fluorine; n denotes 0 or 1; "40 7 denotes SM or СО-А, A denotes OK), ZK" or M(К3)Ка. in c (3) Compounds in which n denotes 0 or 1; from 7 denotes CM or СО-А,

A means OK. or ZK"; and 45 Ki and Ko" denote hydrogen, C-C alkyl, which is unsubstituted or substituted 1 - With halogen atoms, with C3-C cycloalkyl or C.--Socoxy group, C3-Salkenyl, which is unsubstituted or substituted 1 - With halogen atoms, C3- Slalkynyl, C3-Seccycloalkyl or phenyl, benzyl or phenethyl, phenyl rings of which are unsubstituted or contain one or two substituents from the group of halogen, hydroxyl, C --C; alkyl,

He" haloC.-Soalkyl, C4-SoAlkoxy-, haloC-SoAlkoxy- or nitro groups. 50 According to the second method of combining formulas | it is possible to obtain according to scheme 2 through the corresponding benzodithiazolium salts MI or hydroxybenzodithiazolium MI! (Notsbrep-UUeu! Eva, as Neiiegoagepe |Neiiegoagepez) II, part 4; p. 2 et seq. and p. 59 et seq.).

Scheme 2 7 2 in, -, ven

GF) otu, m. ime) As |nyu b2) 2 2 7 60 ZNO (in 8. in -i nya er -on z Ye vho

Mn, M K

GiLly M

Iv (2-SOON) p. in (a) A halide of the series, for example, ZoSiO or ZCI" (where the aniline derivative M is first preferably converted into the corresponding hydrochloride salt) in an inert solvent, for example, in acetic acid, at 0 - 12072 (U. Ogu. Spec. 30 , 2763; 9. Nei. Spet. 3, 518, ibid. 5, 1149). (01) Н»О/ or Н2О/ Maods (0 - 50"C) | Chemistry of heterogeneous compounds (9), 1205 (1979); Zupii. Sott. 23, 2631). (62) НхО/ 20 - 100"С with or without a base such as sodium bicarbonate, sodium carbonate, or a dilute solution of an alkali metal or alkaline earth metal hydroxide or oxide |). At.

Spent Zos. 68, 1594 (1946)). (c) Sulfur dihalide (for example, ZSIi"), thionyl halide (5OSI"), ot - 20 to 10070 (U. Nei. Spet. 3, 518). (4) 5(О)5», where | denotes a leaving group, such as a halogen atom, imidazol-1-yl or 1,2,4-triazol-1-yl, for example, thionyldiimidazole or ZOSI", ie - 30 to 100"C, an inert solvent |). 7/0 Spec. 30, 2763 (1965).

It is also possible to carry out the further interaction of the compounds with the participation of benzodithiazolium salts of MI and MII without dilution and under the corresponding conditions (). Spent boss. 1970, 2250, Noirep-UUeu|! Eva, Negyegoagepe

I, part 4, p. 59 and further (first of all, p. 93 and further) with the preparation of benzothiadiazoles II or Ia.

Scheme 3: conversion of pears; 7,

Resoon -- 52525. in RISOS -- 80 5 vzno moe

R-SO-A RI-SO-MNA in | (is)

РИ-С8-А РН-СМ с до о вн З

RY: so or s-G y -- y

Mn, M c (a) chlorinating agent, for example, OSI" or SOSI"; (5) М-А (II), where M denotes hydrogen, Gi", Ma", K", 1/2mMd" or a quaternary ammonium ion and A has the meaning specified for formula I; "-- (c) a sulfurizing agent, for example, phosphorus pentasulfide or cyclodithiocyanate

Zo 4-methoxyphenylthiophosphonic acid ("Lossson's reagent"); o (4) MN"; (f) dehydration agent, for example, OSI" or SOSI"; () reduction, for example, using hydrogen/catalyst or complex hydride, for example, "

ПАНХОСНСНоОСН»)». The description of the reaction is carried out according to a known technique, for example, in the absence or absence of the corresponding solvent, diluent or their mixture in the medium, and such a reaction, if necessary

It is carried out with cooling, at room temperature or with heating, for example, in the temperature range from about -807C to the boiling point of the reaction mixture, preferably from about -20 to about 1707C, and if necessary in a closed vessel, under pressure, in the atmosphere inert gas and/or in anhydrous conditions.

Mn Processes of diazotization, i.e. the interaction of a primary amine with nitrous acid or with an inorganic or organic nitrite is expediently carried out at a temperature from - 20 to - 30"C.

Leaving groups represent, for example, an atom! fluorine, chlorine, bromine, and iodine, C1-Salkylthio group, such as methylthio-, zylthio-, and propylthio group, C-Salkanoyloxy group, such as acetoxy group, ka 20 (halomd) / -C1-Svalcansulfonyloxy group, such as methanesulfonyloxy-, ztansulfonyloxy- or ah trifluoromethanesulfonyloxy group, substituted or unsubstituted phenylsulfonyloxy group, such as 7" benzenesulfonyloxy- or p-toluenesulfonyloxy group, imidazolyl, triazolyl, hydroxyl or water, preferably chlorine, bromine and iodine atoms and p-toluenesulfonyloxy group.

Corresponding bases are, for example, hydroxides), hydrides, amides, alkanoyls, 25 carbonates, dialkylamides and alkyl silyl amides, alkali metals and alkaline earth metals,

HF) alkylamines, alkylenediamines, non-alkylated and M-alkylated saturated and unsaturated cycloalkylamines, basic heterocyclic compounds, ammonium hydroxide and carbocyclic amines. Examples include hydroxide, hydride, amide, sodium methanolate and carbonate, potassium tert-butanolate and carbonate, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, tristhylamine, 60 tristylenediamine, cyclohexylamine, M-cyclohex-syl- M,M-dimethylamine, M,M-distylaniline, pyridine, 4-(M,M-dimethylamino)pyridine, M-methylmorpholine, benzyltrimethylammonium hydroxide and 1,8-diazabicyclo

И5.4.0Й undec-5-ene (DBU).

It is possible to conduct interaction between reagents as such, i.e. without adding a solvent or diluent, for example, to the melt. However, it is generally recommended to add an inert solvent, such as a diluent or a mixture thereof. Examples of such solvents or diluents are aromatic,

aliphatic and alicyclic hydrocarbons! and halogenated hydrocarbons, such as benzene, toluene, xylene, chlorobenzene, bromobenzene, petroleum sulfur, hexane, cyclohexane, methylene chloride, chloroform, dichloroethane and trichloroethane; simple ethers, such as diethyl ether, tert-butyl methyl ether, tetrahydrofuran and dioxane; ketones, such as acetone and methylzylketone; alcohol", such as methanol, ethanol, propanol, butanol, ethylene glycol and glycerin; compounds such as ethyl acetate and butyl acetate; amide, such as M,M-dimethylformamide, M,M-dimethylacetamide, M-methylpyrrolidone and hexamethylphosphoric acid triamide; a nitrile such as acetonitrile and a sulfoxide such as dimethyl sulfoxide. As solvents or diluents, it is also possible to use an excess of 7/0 Kolychestva base, such as tristhylamine, pyridine, M-methylmorpholine or M,M-distylaniline. Such interaction can also be carried out under the conditions of interfacial catalysis in an organic solvent, for example, in methylene chloride or toluene, in the presence of an aqueous alkaline solution, for example, a sodium hydroxide solution, and an interfacial catalyst, for example, primary acid tetrabutylammonium sulfate.

Typical reaction conditions are presented in the examples.

The invention further relates to the preparation methods given below, and the substituents in the following schemes (1)-(6) represent the substituents indicated in the described scheme 1. (1) The method of obtaining the compound of formulas I or its salts -ch-- - her -- --her

М МН, мн, "и иа and including the interaction of the compound of formulas I! with a hydrogen strong base to obtain the compound of formula Ia or its salt and its subsequent transformation into the compound of formula I. (2) The method of obtaining the compound of formula Ia or its salt 7 soon

A vn o (n f-nl --- same Hip

M MN,

II and including the interaction of the compounds of formulas and! with a strong hydrogen base, in particular with potassium hydroxide solution or sodium hydroxide solution, at a temperature of 120 - 15072 and under a pressure of 1 - Bbar. cm (3) The method of obtaining the combination of the formula (Ce)

IS "-

WITH

IS c) in D-chnyal

M

I « 9 - - sleep 7 I вн вн (n -2 (dp sl 15 Mn, Mn,

Ia i - ») in (o) same in soon 7 ke mo (Ha ( y y

M M

59 Sha (I (F, which includes ka a) interaction of the compound of the formulas and! with a strong hydrogen base to obtain the compound of the formula Ia or its salt and, if necessary, or 60 61) its conversion into the compound of the formulas! By diazotization with nitric acid or organic or inorganic nitrite and under certain conditions, its conversion into a compound of the formula! Ii; or 62) ego conversion into a combination of formulas AND ego conversion into a combination of formulas! III by diazotization with nitric acid or organic or inorganic nitrite. (4) The method of obtaining a combination of formulas! Sha b5

2 soon soon 5H uv -her -x uv

M chn, m " Ia Sha which includes the interaction of the compound of the formulas! II with a strong hydrogen base to obtain the compound of the formulas! inorganic nitrite, where, in particular, the first reaction stage is carried out in a solution of potassium hydroxide at 120 - 1707C and under a pressure of 1 - 5 bar and where diazotization is carried out with sodium nitrite. Ha

M And mn, m ! which includes the hydrolysis of compounds of formulas! MI in neutral or alkaline conditions. (6) A method of obtaining a compound of formula II or its salt

Y Y Z. her. --- yahhk I, Y -- es d-chna

Mn, MN oMNI M

In m "which includes the interaction of the compounds of the formulas! M with ZSM-T or with the 5SM-salt in a solvent and under appropriate conditions in the presence of acids! or bases and the interaction of the compounds of the formulas IM obtained in this way with an oxidant, for example, with ZO 5Si", Hgo ", NeZO//bromide or Si", with obtaining from the compound of the formula ІІ

At the first reaction stage, it is preferable to use S.-Svalkylisothiocyanate, in particular, methyl isothiocyanate; suitable solvents are anhydrous carboxylic acid, for example, formic acid and acetic acid; alcohols, for example, ethanol and isopropanol, ketones, simple ethers and halogenated hydrocarbons.

Both reaction stages are especially preferably carried out in the same solvent, for example, in acetic acid, and without leaching of the IM compound.

In addition, the invention relates to new semi-products of the formulas ЯИ and ИМ и-о 7 and 7 "- are d-chni i. I eat her

M MN Osmnt and M or their salts, where

X denotes fluorine, n denotes 0, 1, 2 or 3; z c t denotes hydrogen, C3-Salkyl, C3-Svalkenyl, C3-Svalkynyl, C3-Svecycloalkyl or substituted or unsubstituted phenyl, benzyl or phenethyl; from 7 denotes CM, СО-А or С5-А,

A denotes hydrogen, halogen, OK, ZK" or M(Kz)Ka;

K.-Ki denote hydrogen, a substituted or unsubstituted, saturated or unsaturated hydrocarbon radical with an open chain containing no more than 8 carbon atoms, a substituted or unsubstituted cyclic saturated or unsaturated hydrocarbon radical containing no more than 10 carbon atoms, substituted or unsubstituted benzyl or phenethyl, a substituted or unsubstituted b alkanoyl group containing no more than 8 carbon atoms, a substituted or unsubstituted benzoyl group, or a substituted or unsubstituted heterocyclic radical, or Kz and K/ together with the nitrogen atom to which they are connected represent a 5- or β-substituted or unsubstituted heterocyclic radical containing 1 - C heteroatom O, 5 and/or M; and with the exception of such compounds of formulas II and M, where 7 denotes СООН or СООС»ОНБб, п denotes 0 and T denotes hydrogen (already known from the Ukrainian Chemical Journal, volume 22, 363, 1956; on which there is a link in Spet. Arbrzig. 22, 43586, dated 1951).

Preferable compounds of formulas II, IM and MI are compounds in which (Ф) n denotes 0 or 1; ka t denotes hydrogen or C.i.C.alkyl; 7 denotes CM or СО-А, and A denotes OK. ZK" or M(Kz)Ka; and

K./-Ku have higher meanings; and among them more preferable connections, in which

A means OK. or ZK";

Ku and Ko" each denote hydrogen, C-C alkyl, which is unsubstituted or substituted 1 - With halogen atoms, 65 C3-C cycloalkyl or C.-Soalkyloxy group, C3-C.alkenyl, which is unsubstituted or substituted 1 - With halogen atoms, C3- Slalkynyl, C3-C. cycloalkyl or phenyl, benzyl or phenethyl, phenyl ring which is unsubstituted or contains one or two substituents from the group of halogen, hydroxyl, C 4-C; alkyl, haloC.-Soalkyl, C-Soalkoxy-, halo C- Soalkoxy or nitro group; and among them the most preferred compounds, in which n denotes 0;

T denotes hydrogen or methyl; 7 denotes CO-A,

A stands for OKU, i

Ki denotes hydrogen, C.--Salkyl, which is unsubstituted or substituted 1 - With halogen atoms, 7/0 C1-Coalkoxy group, C3-Scycloalkyl or phenyl, benzyl or phenethyl, phenyl ring which is unsubstituted or contains one or two substituents from the halogen group .

In compounds of formulas MI Na! preferably chlorine.

Samples of receipt

Example 1: 3-amino-2-mercaptobenzoic acid (formula Ia1) 28.9 g of 85956 potassium hydroxide dissolved in 1 ml of water was added dropwise to 3.5 g of methyl-2-aminobenzothiazol-7- carboxylate in Zvml of dioxane with simultaneous stirring and cooling with ice in such a way that the internal temperature did not exceed 2576.

After that, the mixture was boiled with a reflux condenser at a bath temperature of 140"C, and by the end of the reaction, the internal temperature was increased to 170"C and dioxane was distilled off using a horizontal condenser.

Then the mixture was cooled to 0"C, filtered in a nitrogen atmosphere, and the residue was washed with 30 ml of water and ice.

The compound specified in the title can be isolated from the filtrate by acidification to pH 5.5 with sharp cooling and stirring at a maximum temperature of 0"C, extraction with ethyl acetate/tetrahydrofuran (8:2) and washing with a concentrated sodium chloride solution. Due to the danger of disulfide formation in further, it is preferable to carry out a direct interaction with the participation of potassium salt in the filtrate (potassium 3-amino-2-mercaptobenzoate). i)

Example 2: benzo-1.2.3-thiadiazole-7-carboxylic acid

The filtered aqueous solution, obtained as a result of the above-mentioned hydrolysis of 17.bmmol of methyl-2-aminobenzothiazole-7-carboxylate, potassium salt of 33-amino-2-mercaptobenzoic acid, was acidified with "-zo" in a nitrogen atmosphere at a maximum temperature of 0"С 31, bml of concentrated sulfuric acid! with simultaneous thorough mixing and sharp cooling, a solution of 1.28 g (18.6 bmmol) of sodium nitrite in 33.4 ml of water was added dropwise under the surface! at a maximum temperature of 10"7C and then the mixture was stirred for 4 h, allowing the temperature to rise to approximately 2573. The formed precipitate was filtered off, washed with ice water and dissolved in tetrahydrofuran, and after treatment with activated carbon, the mixture was filtered on a small amount of silica gel. After evaporation of the filtrate, 2.64 g (8895 in 2 stages) of the gray compound specified in the title with a melting point of 232 - 233"C were obtained. Analysis using high-pressure liquid chromatography showed a content of at least 8390 of the title compound and approximately 8 - 1795 of the isomeric benzo-1,2,3-thiadiazole-5-carboxylic acid. Recrystallization from dioxane gave the pure compound specified in the title with a "melting point of 239 - 240"C. with c Example 3: benzo-1,2,3-thiadiazole-7-carbonide chloride 290 g of benzo-1,2,3-thiadiazole-7-carboxylic acid were suspended in 1.bl of toluene, 3.5 mL were added; of dimethylformamide and 129U9 ml of thionyl chloride, and the mixture was stirred at 80-90°C, and as the gas evolved, the suspension turned into a solution. After the reaction was complete, the solution was cooled and filtered through a small amount of Nouillet material, the residue was washed with toluene, and the filtrate was evaporated. As a result, 297g (9395) of crude acid chloride, which can be used directly for the reaction in the future - Example 4: 5-methylbenzo-1,2,3-thiadiazole-7-thiocarboxylate

2100 ml of trisethylamine and 2.1 g of 4-dimethylaminopyridine were added at 0"C to a solution of 60.7 g (1.2 bmol) of 5 g of methyl mercaptan in 1450 ml of methylene chloride. At 0 - 5 C, 250.1 g ( 1.2 bmol) of the above-mentioned acid chloride, dissolved in 1.2 l of chloride

Kk of methylene, and then the mixture was stirred at room temperature for 3h. Next, water with ice was added, the aqueous phase was extracted with methylene chloride, and the organic extracts were combined! washed with water, dried over sodium sulfate, filtered through a small amount of silica gel and evaporated. In this way, 236 g (8990) of 5-methylbenzo-1,2,3-thiadiazole-7-thiocarboxylate with a melting point of 132 - 13476 were obtained.

F) Example 5: methyl-3-aminobenzoate, 13 Oml (1.7 vmol) of sodium chloride was added dropwise while stirring to 500 ml of methanol, which had previously been cooled to -5°C, and the mixture was thoroughly stirred at 07°C for 5 min. Then, at the same temperature, 70 g (0.5 mol) of solid 3-aminobenzoic acid was introduced, the mixture was stirred for 15 min, and the resulting solution was heated to 707 C and kept at the same temperature overnight. and by adding a saturated solution of sodium bicarbonate, the pH was brought to 7.5. The product was extracted with ethyl acetate and the extract was washed with water, dried over sodium sulfate and evaporated. In this way, 65 69.8 g (92.296) of pure methyl sulfur was obtained in the form of an oil, which on standing crystallizes, melting point 37 - 3870.

Example 6: methyl-Z-tisureidobenzoate

First, 11.3 g of methyl-3-aminobenzoate in the form of a solution in 75 ml of chlorobenzene was introduced into the reaction vessel.

At a temperature of -5 to 0"C, 2.07 ml of concentrated (96905-noy) sulfuric acid was added dropwise for 15 minutes, stirring was continued for 5 minutes, then in separate portions at a maximum temperature of 0"C, 6b.8g of sodium thiocyanate and a mixture additionally stirred for 15 minutes.

Next, 0.2 ml of 15-crown-5 was added, the mixture was stirred at a bath temperature of 1007"C for 10 hours, cooled, and the resulting precipitate was filtered off and washed three times with water. In this way, 13.5 g (85.9965) of the title compound was obtained with a melting point of 171 - 17276. 70 Example 7: methyl-2-aminobenzothiazole-7-carboxylate 8.4 g of methyl-3-tisureidobenzoate was suspended in 120 ml of chlorobenzene, at 0"C for 1 hour, 2.2 ml of bromine was added to 30 ml of chlorobenzene at the same time as much as possible possible thorough mixing, after which the mixture was stirred at room temperature. Then it was kept at 70"C for 4 hours, cooled, a small amount of distilled sulfur was added, the precipitate was filtered off, thoroughly mixed with 7 Oml of an aqueous solution of sodium bicarbonate, filtered again and washed with water. In this way, 7.7 g (88905) of a gray product was obtained with a melting point of 231 - 232". HPLC analysis in addition to 8 - 1895 of isomeric methyl-2-aminobenzothiazole-5-carboxylate showed the content of more than 8395 of the pure compound indicated in the title. By suspending in ethyl acetate, holding for a short time at 70°C, cooling to 30°C, and filtering, the pure compound specified in the title with a melting point of 25070 was obtained.

If such a reaction is carried out in acetic acid (and not in chlorobenzene), then the content of the undesirable isomeric methyl-2-aminobenzothiazole-5-carboxylate is only approximately 590.

Example 8: direct preparation of benzo-1,2,3-thiadiazole-7-carboxylic acid from methyl-2-aminobenzothiazole-7-carboxylate

M Mn, M 1.3 kg of methyl-2-aminobenzothiazole-7-carboxylate was kept at 1207C / 1 - 2 bar in 3.5 kg of 5095 KOH for 4 hours, and then at 0 - 5"C the mixture was neutralized with an aqueous solution of hydrochloric acid. 4095 aqueous solution of sodium nitrite was added to the solution at pt. at a temperature of 07C to 107C, and the product that precipitated was filtered, washed and dried. In this way, 1.03Zkg cm benzo-1,2,3-thiadiazole was obtained -7-carboxylic acid with a melting point of 230 - 233" (the 9190th input from (se) theoretical in two stages).

Example 9: direct preparation of benzo-1.2.3-thiadiazole-7-carboxylic acid from -- 2-methylaminobenzothiazole-7-carboxylic acid IS) son son sooNn 5 vn B,

Sun Os tt So ; : "

Suspension 150g of 2-methylaminobenzothiazole-7-carboxylic acid! (concentration 92.790) and 596g of 47905

KOH was kept at 1552 / 1.7 - 1.8 bar in an autoclave for 12 hours, and then clarified by filtration at 20 - 2570 °C. The filtrate was added dropwise to 635 g of 3795 hydrochloric acid and 500 ml of methanol was added. 200g of a 3095% aqueous solution of sodium nitrite was added dropwise from the suspension at a temperature of -10 to -5"C and the mixture was allowed to react completely at a temperature of -5 to 0"C for 2 hours. By vacuum filtration and washing with water, 112 g of gray benzo-1,2,3-thiadiazole-7-carboxylic acid was obtained! with a melting point of 260 - 2627. HPLC-analysis showed a content of 90 - 9395 pure specified in the title compound. - Example 10: obtaining 3-amino-2-mercaptobenzoic acid! 1.3 g. of methyl-2-amino-7-methoxycarbonylbenzoate in a nitrogen atmosphere with simultaneous stirring

Me. 3.4 g of a 5095% solution of potassium hydroxide was introduced into 3.4 g of potassium hydroxide solution and the mixture was kept in a casing for sealed glass for 20 ampoules! at 120°C for 12 hours. Then the mixture was cooled, an additional 1.3 g of 5096% potassium hydroxide solution was added in an inert atmosphere, and the mixture was additionally kept at 1507°C for 4 hours. Then the mixture was cooled dropwise in an inert atmosphere at 0 An amount of diluted sulfuric acid was added to it, which is sufficient to achieve a pH of 5.5. The precipitate formed was filtered and washed with ice water. After drying in a deep vacuum, the compound indicated in the title of 22 with a melting point of 255 - 2582С was obtained, which according to the data mass spectrometry

F! contained traces of the corresponding disulfide.

Example 11: preparation of 3-(M'-methyltisureido)benzoic acid! how soon

With bo r sn,

MN us

A mixture of 279.6 g of Z-aminobenzoic acid! with 164.1 g of methyl isothiocyanate and 1000 g of 100956-noy acetic acid were heated to 80 - 85"C. The temperature rose to 95 - 1007C within 20 minutes without further heating and a transparent solution was formed from which the product slowly crystallized. The suspension was kept at 90 - 100 for 2 hours, after which it was cooled to 15-20"C, filtered under vacuum and the residue on the vacuum filter was washed with acetic acid. In this way, 404 g of the title compound with a purity of 99.596 were obtained; melting point 190 - 1917 (decomposition). Output: 95,795 from the theoretical.

Example 12: preparation of 2-methylaminobenzothiazole-7-carboxylic acids soon 5 s /Zh-mn-sn,

M

76 Solution of 163g of bromine and 50g of 10095-noy acetic acid! 212g of 3-(M'-methyltisureido)benzoic acid and 500g of 100956-acetic acid were added dropwise to the suspension at 45 - 50"C for 2 hours. Then the mixture was heated to 90 - 1007C for 2.5 hours and the reaction was allowed to proceed in during the next 2 hours until the gas evolution stops. After distilling 150g of acetic acid at 80-857C under reduced pressure, 200g of water was added, and the pH value of the mixture was brought to 7/5 by dropwise addition of a 3095 solution of sodium hydroxide to 2. As a result of filtration under vacuum at 70 - 807C and washing with water yielded 179.2 g of the title compound with a melting point of »330"C. HPLC analysis in addition to C - 4965 isomeric 2-methylaminobenzothiazole-5-carboxylic acid showed a content of 94.695% of the title compound. Output: 81,595 from theoretical.

Example 13: preparation of 2-methylaminobenzothiazole-7-carboxylic acid! without elimination of an intermediate product (reaction in one reactor) soon soon soon 5 hours

Mn, mi nnsn, M

A solution of 39.2 g of methyl isothiocyanate and 50 g of 10095 acetic acid! at 75 - 80"C, 70g of 3-aminobenzoic acid and 250g of 100956-acetic acid were added dropwise to the suspension in the flow of BOMin. 3-(M'-methyltisureido) The reaction was allowed to proceed to completion within 2 hours, after which the mixture was cooled to 50°C and a solution of 81.5 g of bromine and 50 g of 100956-noy acetic acid was added dropwise within 2 hours at 45-50°C.

Next, the mixture was heated for 2 hours to 90 - 100"7C and the reaction was allowed to complete for 2h4 until it stopped - gas was released. After distillation under reduced pressure and at 75 - 802C, 160g of acetic acid was added to the residue with 200g of water, 67g was added dropwise. 3095 solution of sodium hydroxide, the mixture was filtered under vacuum at 75-807C and the residue was washed with water, obtaining 7g of a product with a melting point of »330C. ise)

HPLC analysis in addition to 0.795 isomeric 2-methylaminobenzothiazole-5-carboxylic acid! showed "- content 9795 of the connection specified in the title. Input: 6895 from theoretical.

From Example 14: methyl-3-amino-2-mercaptobenzoate o сОоОМе сООМе вн 0 - i; p

M Mn, o c A solution of 1 g of methylbenzo-1,2,3-thiadiazole-7-carboxylate in 40 ml of dioxane was hydrogenated over 0.5 g of 595 palladium on charcoal at 1607"С and an initial pressure of 150 bar. After the reaction of the starting substance was completed, » the catalyst was filtered off, washed with dioxane, the filtrate was evaporated, avoiding contact with air, and the residue was purified on silica gel. in the examples, you can get the compounds presented in the following tables.

Claims (1)

The formula of the invention with 50 - and 1. Derivative of Z-amino-2-mercaptobenzoic acid! formulas I VN o F) MN. He A is ego disulfide or ego salt, where X denotes fluorine, n denotes 0, 1, 2 or 3, 7 denotes CM, СО-А or С5-А, A denotes hydrogen, OKU, ZK» or M(К3)Ка , K.-Ki denote hydrogen, a substituted or unsubstituted, saturated or unsaturated 65 hydrocarbon radical with an open chain containing no more than 8 carbon atoms, a substituted or unsubstituted cyclic saturated or unsaturated hydrocarbon radical containing no more 10 carbon atoms, substituted or unsubstituted benzyl or phenethyl, substituted or unsubstituted alkanoyl group containing no more than 8 carbon atoms, substituted or unsubstituted benzoyl group or substituted or unsubstituted heterocyclic radical; or Ez and Ku together with the nitrogen atom with which they are bonded denote a 5- or b-substituted or unsubstituted heterocyclic radical containing 1-3 O, 5 and/or M heteroatoms, except for compounds in which n denotes 0 and 7 denotes SM or СОМН», or СООН. 2. Derivative according to claim 1, characterized by the fact that 7 denotes СМ, СО-А or С5-А, 70 А denotes hydrogen, ОК, ЗКо or М(Бз3)Ка, and where Ки, Ко and Кз each denote hydrogen, Si -Salkyl, which is unsubstituted or substituted by 1-5 halogen atoms, C3-C8cycloalkyl, C.i.i.C; alkoxy-, phenoxy-, benzyloxy-, C.i.i. C-C.alkanoyl, benzoyl, carboxyl, C.i-C;alkoxycarbonyl, benzyloxycarbonyl, amino-, C.--Slalkylamino-, C.i-C.dialkylamino group or heterocyclyl, 7/5 C3-Svalkenyl, which is unsubstituted or substituted by 1-5 halogen atoms, C3-Svalkynyl, C3-Svecycloalkyl, S.-C.alkanoyl, phenyl, benzyl or phenethyl, phenyl ring of which are not substituted! or contain from one to three substituents from the groups! halogen, hydroxyl, C1-C1alkyl, C1-C1-Coalkyl, C1-C1-Coalkyl, C1-C1-Coalkyl, C1-C1-Coalkyl, or nitro groups, or naphthyl, benzoyl, or heterocyclyl, which is unsubstituted! or substitution by one or three identical or different substituents from the groups! halogen, C 4-Coalkyl, 2o-halidemethyl or nitro group, Ku denotes hydrogen, C-Calkyl, phenyl or benzyl, or Ez and Ku together with the nitrogen atom with which they are connected, represent a 5- or b-lennoe ring with 1-2 heteroatoms 0, 5 and/or M, where the indication of the ring is unsubstituted or contains one or two identical or different substituents from the groups! halogen, C1-S6alkyl or C1-S6-Alkoxycarbonyl. with C. Derivative according to claim 2, characterized by the fact that n denotes 0 or 1, (8) 7 denotes СМ or СО-А, А denotes hydrogen, ОК, ЗКо or М(Бз3)Ка, and where K./-Ku have the meanings indicated in claim 2. "- zo 4. A derivative according to clause 3, distinguished by the fact that n denotes 0 or 1, c 7 denotes CM or CO-A, "o A denotes hydrogen, OK . or ЗК» and Ки and Ко» each denote hydrogen, C.--C alkyl, which is unsubstituted or substituted by 1-3 atoms -- with a halogen, C-C-C cycloalkyl or a C.-Co-alkyloxy group, C-C-Salkenyl, which is unsubstituted or substituted by 1- with 3 halogen atoms, C3-Slalkynyl, C3-Svecycloalkyl or phenyl, benzyl or phenethyl, phenyl rings of which are unsubstituted or contain one or two substituents from the groups! halogen, hydroxyl, C and -C; alkyl, haloC.-Soalkyl, C4-SoAlkoxy-, haloC -SoAlkoxy- or nitro group. 5. The method of obtaining a derivative of the formula I or its salt « sosNn 8 s « 8n en z ox D-MNLI -- bu -- o " MH, Mo p Ia I 1 including the interaction of the compound of the formula II, where - X, p and 7 have values, the indication for formulas I and T denotes hydrogen, C1-C6alkyl, C3-C6alkyl, C3-C6alkyl, C3-C6cycloalkyl, substituted or (e)) unsubstituted phenyl, benzyl or phenethyl, which is treated with a strong aqueous base to obtain compounds of formulas Ia or its salts and their subsequent interaction with obtaining compounds of formula i, where X, p and 7 have the meanings indicated for formulas I. -. and 6. The method of obtaining a derivative of the formula Ia or its salt soon 2 chai tutchnya vu Mko p La "7 including the interaction of the compound IY, where 60 X, p and 7 have meanings, the indication for the formulas I, and T denotes hydrogen, C. 1-Salkyl, C3-Salkyl, C3-Salkyl, C3-Scycloalkyl, substituted or unsubstituted phenyl, benzyl or phenethyl, with a strong base. 7. The method according to item b, characterized by the fact that a solution of potassium hydroxide or a solution of sodium hydroxide is used as a base. 8. The method according to claim 6, characterized by the fact that the reaction is carried out at 120-150" under a pressure of 1-5 bar. 9. The method of obtaining a derivative of formula II, where X, p and 7 have meanings, the designation for formulas I, and T denotes hydrogen, C3-Salkyl, C3-Salkylenyl, C3-Salkylenyl, C3-Seccycloalkyl or substituted or unsubstituted phenyl, benzyl or phenethyl, KU SOU D-mnl M p sFOoon en eN ha so OO " MN. Mn, I Ia Te | B) c sleep i) KU 5 x I2U9 ve 0, Х vo, these h- M M Sha shSh with which includes (Se) a) interaction of compounds of formulas II, where - X, p and 7 have meanings, indications for formulas I , and T denotes hydrogen, C3-C6alkyl, C3-C6alkyl, C3-C6alkyl, C3-C6cycloalkyl or substituted or M unsubstituted phenyl, benzyl or phenethyl, with a strong hydrogen base to obtain compounds of the formulas! Ia or ego salts and if necessary either « 61) conversion of ego into a combination of formulas! By diazotization with nitric acid or inorganic or organic nitrite and under certain conditions, its conversion into a compound of the formula! III, or - p. 62) ego conversion into a combination of formulas I and ego conversion into a combination of formulas! It is diazotized with nitric acid or inorganic or organic nitrite. ," 10. The method of obtaining the derivative of formulas! Ia, soon cOoson 35 « вн 8 1 x СО я-МНl -- (du -- 004 "М - М M (22) p Id "Sha GI 50 which includes the interaction of compounds of formulas Ii, where X, p and 7 have meanings , the indication for formulas I, and "Z T denotes hydrogen, C3-Salkyl, C3-Salkylenyl, C3-Salkylynyl, C3-Scycloalkyl or substituted or unsubstituted phenyl, benzyl or phenethyl, with hydrogen and a strong base to obtain compounds of formulas Ia or Ego salt and its conversion 5o directly, i.e., without elimination, into a compound of the formulas !Sa by diazotization with nitric acid or Ф! with an inorganic or organic nitrite. 11. The method according to claim 10, characterized by the fact that the first stage of the reaction is carried out in a solution of potassium hydroxide at 120-170"7C and under a pressure of 1-5 bar, and where diazotization is carried out with sodium nitrite. 12. The method of obtaining a derivative of the formula I 60 gen u niz o 7 Na oh M MH 65 M I which includes the hydrolysis of the compound of the formulas! MI, where X, n and 7 have the meanings specified for formula I, in neutral or alkaline conditions. 13. The method of obtaining a derivative of the formula II or its salt is KU so, -- o, 0-5 o r-knt ю МН, МНОСМН-Т М У I ny which includes the interaction of the compounds of the formulas! M with ZSM-T or with 5SM-salt in a solvent and under appropriate conditions in the presence of acid! or the bases and interaction of the compounds of the IM formulas obtained in this way with an oxidant, for example, with ZO 5Si», HgO», NeZO//bromide or Si», with obtaining 72 compounds of the formulas! II, in which X, p, 7 and T have the meanings specified in clause 5. 14. The method according to claim 13, characterized by the fact that methyl isothiocyanate is used at the first stage of the reaction, and HO is used at the second stage of the reaction, and where both reaction stages are carried out in anhydrous carboxylic acid and without extracting the IM compound. 15. 3-amino-2-mercaptobenzoic acid derivative! of the formula II 20 5 so l-kilt M c z p o) or its salt, where X denotes fluorine, n denotes 0, 1, 2 or 3, "- zo T denotes hydrogen, C-Salkyl, C3-Salkylenyl, C3- Svalkynyl, C3--Secycloalkyl or substituted or unsubstituted phenyl, benzyl or phenethyl, c 7 denotes CM, СО-А or С5-А, "о A denotes hydrogen, halogen, ОК), ЗК" or М(Кз)Ка, VK.-K/ denote hydrogen, substituted or unsubstituted, saturated or unsaturated (87 35 hydrocarbon radical with an open chain containing no more than 8 carbon atoms, substituted or unsubstituted cyclic saturated or unsaturated hydrocarbon radical containing no more carbon atoms, substituted or unsubstituted benzyl or phenethyl, substituted or unsubstituted alkanoyl group containing no more than 8 carbon atoms, substituted or unsubstituted benzoyl group or substituted or unsubstituted heterocyclic radical, or "Kz and KK; together with the nitrogen atom with which they are connected, they represent 5 - or b-membered C-substituted or unsubstituted heterocyclic radical containing 1-3 O, 5 and/or M heteroatoms, with the exception of compounds in which 7 denotes СООН or СООСОН, n denotes 0 and T denotes hydrogen. 16. Derivative according to claim 15, characterized by the fact that X denotes fluorine, c n denotes 0 or 1, t denotes hydrogen or C.i.C. alkyl, - 7 denotes CM or CO-A, He» and A denotes hydrogen, halogen, OK , ZK" or M(K3)KaA and K./-Ku have the meanings indicated in claim 2. where 17. Derivative according to claim 16, characterized by the fact that A means OK. or ZK" and Ki and Ko" each denote hydrogen, C-C alkyl, which is unsubstituted or substituted by 1-3 halogen atoms, C-C cycloalkyl or C-C alkyloxy group, C-C alkyl, which is unsubstituted or substituted by 1-3 atoms by halogen atoms, C3-Slalkynyl, C3-Secycloalkyl or phenyl, benzyl or phenethyl, phenyl rings which are unsubstituted or contain one or two substituents from the groups! halogen, hydroxyl, C and -C; alkyl, F) haloC1-Coalkyl, C41-C0-Alkoxy, haloC1-CoAlkoxy- or nitro group!. ka 18. Derivative according to claim 17, characterized by the fact that n denotes 0, 60 T denotes hydrogen or methyl, 7 denotes CO-A, A denotes OK and Ki denotes hydrogen, C-C-C alkyl, which is unsubstituted or substituted 1-3 halogen atoms, C.-Soalkoxy group, C3-Svecycloalkyl or phenyl, benzyl or phenethyl, phenyl rings of which b5 are unsubstituted or contain one or two substituents from the groups! halogen, hydroxyl, C 1-C alkyl, C 1-C alkyl, C 4 C-C alkyl, C 1-C alkyl, or nitro group. 19. Derivative of 3-amino-2-mercaptobenzoic acid! of the formula IM NI K mno Mn-T T/ or its salt, where X denotes fluorine, n denotes 0, 1, 2 or 3, T denotes hydrogen, C3-Salkyl, C3-Svalkenyl, C3-Svalkynyl, C3-Seccycloalkyl or substituted or unsubstituted phenyl, benzyl or phenethyl, 7 denotes CM, СО-А or С5-А, A denotes hydrogen, halogen, OK), ЗК» or М(Кз)Ка, K.i-K. each denote hydrogen, a substituted or unsubstituted, saturated or unsaturated hydrocarbon radical with an open chain containing no more than 8 carbon atoms, a substituted or unsubstituted cyclic saturated or unsaturated hydrocarbon radical containing no more than 10 carbon atoms, a substituted or unsubstituted benzyl or phenethyl, a substituted or an unsubstituted alkanoyl group containing no more than 8 carbon atoms, a substituted or unsubstituted benzoyl group, or a substituted or unsubstituted heterocyclic radical, or Ez and Ku together with the nitrogen atom to which they are bonded denote a 5- or b-substituted or unsubstituted heterocyclic a radical containing 1-3 heteroatoms O, 5 and/or M, except for the compound where 7 denotes СООС»Нб, n denotes 0 and T denotes hydrogen. with 20. Derivative according to claim 19, characterized by the fact that d) n denotes 0, t denotes hydrogen or C.i-Salkyl, 7 denotes CO-A, and A denotes OK. и - Ki denotes hydrogen, C.i-Salkyl, which is unsubstituted or substituted by 1-3 halogen atoms, c C.-Coalkoxy group, C3-Svecycloalkyl or phenyl, benzyl or phenethyl, phenyl ring which is unsubstituted or contains one or two substituents from the group of halogen, hydroxyl, C--C; alkyl, ise) haloC.-Coalkyl, C4-Co»alkoxy -, haloidC - Coalkoxy- or nitro groups. - From the Official Bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated circuits", 2002, M 12, 15.12.2002. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. - . and? 1 - (o) name) - name) 60 b5