RU2059612C1 - Method of synthesis of 1-phenyl-1-para-nitrobenzoylamino-5-n,n- diethylaminopentane hydrochloride and 1-phenyl-1-amino-5-n,n- diethylaminopentane - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: product 1: 1-phenyl-1-p-nitrobenzoylamino-5-N, N-diethylaminopentane hydrochloride. Reagent 1: 1-phenyl-1-amino-5-N, N-diethylaminopentane. Reagent 2: p-nitrobenzoyl chloride. Reaction conditions: in the medium of anhydrous aprotonic solvent at temperature from 0 C to the boiling point. Product 2: 1-phenyl-1-amino-5-N,N-diethylaminopentane. Reagent 1: 1-phenyl-1-cyano-1-carbethoxy-5-bromopentane. Reagent 2: diethylamine. Reaction conditions: at boiling followed by saponification and decarboxylaton of product prepared, acid or alkaline hydrolysis of formed product with bromine in methanol medium in the presence of sodium methylate at temperature from (-1) C to the boiling point, or with bromosuccinimide in the presence of mercury acetate in the mixture of dimethylformamide and methanol and boiling prepared product in spirituous-alkaline medium. EFFECT: improved method of synthesis. 1 cl, 1 tbl

Description

Соединение I обладает антиаритмической и антифибрилляторной активностью.The invention relates to the chemistry of both N-substituted amides of aromatic carboxylic acids and substituted amines, and relates specifically to an improvement in the method for producing 1-phenyl-1-n-nitrobenzoylamino-5-N, N-diethylamino-pentane hydrochloride of formula I

Compound I has antiarrhythmic and antifibrillatory activity.

 The purpose of the invention is a method for producing compound I.

 The essence of the proposed method is that the target product I is obtained directly by reacting the starting compound 1-phenyl-1-amino-5-N, N-diethylaminopentane with n-nitrobenzoyl chloride in an anhydrous aprotic solvent.

The claimed process for preparing the compounds I is that 1-phenyl-1-amino-5-N, N-dietilaminopentan reacted with n-nitrobezoilhloridom in an anhydrous aprotic solvent at a temperature ranging from 0 C to ^the reflux temperature of the reaction mass.

Target product I is isolated in the usual way. Compound I is obtained in the form of a light yellow or light yellow with a greenish tinge of crystalline powder, soluble in water, chloroform and alcohol, practically insoluble in ether with so pl. 165-167 ^{° C} (from isopropanol) 73,1-92,6% yield based on the 1-phenyl-1-amino-5-N, N-dietilaminopentan.

I 92,6%
В качестве безводного апротонного растворителя используют ароматические углеводороды, например бензол, эфиры, например этилацетат, кетоны, например ацетон, предпочтительно нитрилы, например ацетонитрил.The scheme of the proposed method for producing compound I

I 92.6%
Aromatic hydrocarbons, for example benzene, ethers, for example ethyl acetate, ketones, for example acetone, preferably nitriles, for example acetonitrile, are used as an anhydrous aprotic solvent.

 The presence of the tertiary amine function in 1-phenyl-1-amino-5-N, N-diethylaminopentane suggested that its interaction with n-nitrobenzoyl chloride can proceed along the tertiary amine group with the formation of the quaternary acyl derivative, and the process could stop at this stage, however, this was not observed. Therefore, the result was not obvious.

 Physico-chemical characteristics of the target product I are shown in the table.

 The second object of the invention is a new method for producing 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII).

 The purpose of the invention is the starting compound for the synthesis of compound I.

The goal is achieved by the proposed method for producing compound VII, namely, that 1-phenyl-1-cyan-1-carbethoxy-5-bromopentane (II) is treated with diethylamine at boiling (65-75 ^about C), the resulting 1-phenyl -1-cyan-1-carbethoxy-5-N, N-diethylaminopentane (III) is saponified and decarboxylated, the resulting 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV) is subjected to acid or alkaline hydrolysis, obtained 1 -phenyl-1-carbamido-5-N, N-diethylaminopentane (V) is treated with bromine in methanol in the presence of sodium methylate in the temperature range m (1) ^on to the reflux temperature of the reaction mass or bromosuccinimide in the presence of mercuric acetate in a mixture of dimethylformamide (DMF) and methanol, the resulting 1-phenyl-1-karbometoksiamino-5-N, N-dietilaminopen- tang (VI) is refluxed alcohol-alkaline environment in the presence of an interphase catalyst, for example, tetraethylbenzylammonium chloride (TEBAH) or without it.

Get compound VII in the form of a colorless or colorless with a light yellow tint oily liquid with so Kip. 117 ^about With at 0,022 mm RT.article

 The yield of compound VII is 25.3% 42.3%, counting on II.

 The scheme of the proposed method for producing 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII).

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Омыление и декарбоксилирование 1-фенил-1-циан-1-карбэтокси-5-N,N-диэтил- аминопентана (III) проводят, как при кипячении с этилатом натрия в этаноле или с хлоридом щелочного металла, например, хлоридом натрия или хлоридом лития, в среде водного диметилсульфоксида (ДМСО), так и с водным раствором едкой щелочи в присутствии межфазного катализатора, например, ТЭБАХа, как в среде ароматического растворителя, так и без него в температурном интервале от комнатной температуры до 50^оС.

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Saponification and decarboxylation of 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane (III) is carried out as when boiling with sodium ethoxide in ethanol or with an alkali metal chloride, for example, sodium chloride or lithium chloride , in aqueous dimethyl sulfoxide (DMSO) and an aqueous solution of caustic alkali in the presence of a phase transfer catalyst, e.g., TEBAHa as in an aromatic solvent, and without it in a temperature range from room temperature to 50 ° ^C.

Acid hydrolysis of 1-phenyl-1-cyano-5-N, N-dietilaminopentana (IV) is carried out in the presence of hydrochloric acid at a temperature ranging from room temperature ^to 50 ° C or in the presence of sulfuric acid at 0-50 ^C.

Alkaline hydrolysis of compound IV is carried out in the presence of caustic alkali and hydrogen peroxide in a medium of DMSO in the temperature range from 5 ^{° C} to room temperature or in the presence of potassium tert-butoxide under reflux.

 Starting compound II is new, not previously described.

 The synthesis of compound II is based on the well-known reaction of obtaining the sodium salt of phenylcyanoacetic acid ethyl ester followed by its alkylation with 1,4-dibromobutane at room temperature or by heating.

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Получают соединение II с выходом 86,3% считая на цианистый бензил.Compound II is obtained by reacting benzyl cyanide with diethyl carbonate in the presence of sodium ethylate during boiling, the resulting corresponding sodium salt of phenylcyanoacetic acid ethyl ester is treated with 1,4-dibromobutane according to the following scheme:

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Compound II was obtained in 86.3% yield, based on benzyl cyanide.

 As starting compounds for the preparation of compound II, benzyl cyanide and diethyl carbonate produced by the domestic industry are used. Intermediates III, IV, V, VI are new compounds not described in the literature.

 Physico-chemical characteristics of compounds II-VII are shown in the table.

 Examples illustrating the claimed method for producing 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII) and its use as a starting product for the synthesis of 1-phenyl-1-n-nitrobenzoylamino-5-N, N- hydrochloride diethylaminopentane (I) are given in the Appendix.

 Based on the claimed methods for producing compounds VII and I, an industrial production of a domestic potential drug (compound I) with antiarrhythmic and antifibrillator activity will be created.

 Example 1. Preparation of 1-phenyl-1-n-nitrobenzoylamino-5-N, N-diethylaminopentane hydrochloride (I).

 I. In the environment of anhydrous acetonitrile.

1) To 20 g of 90% or 18 g (0.0768 mol) of 100% 1-phenyl-1-amino-5-N, N-diethylaminopentane is added 20 ml of anhydrous acetonitrile, stirred for 10 minutes at room temperature, then cooled to 0-5 ^{° C} and at this temperature a solution of 16.63 g of 90% or 14.97 g (0.0807 mol) of 100% n-nitrobenzoyl chloride in 46 ml of anhydrous acetonitrile. When the download is n-nitrobenzoyl chloride, the reaction mixture was stirred for 4 hours at 0-5 ^C. The precipitate was filtered off, washed with 30 ml of absolute isopropanol and dried to constant weight.

Obtain 29.96 g (93%) of 99.5% hydrochloride of 1-phenyl-1-n-nitrobenzoylamino-5-N, N-diethylaminopentane (I) or 29.81 g (92.6%) in terms of 100% content of I, counting on 1-phenyl-1-amino-5-N, N-diethylaminopentane. Mp 165-167 ^{° C} (from absolute isopropanol).

2) To 20 g of 90% or 18 g (0.0768 mol) of 100% 1-phenyl-1-amino-5-N, N-diethylaminopentane is added 20 ml of anhydrous acetonitrile, stirred for 10 min at room temperature, then cooled to ^0-5 ° C and a solution of 16.63 g of 90% or 14.97 g (0.0807 mol) of 100% n-nitrobezoilhlorida in 46 ml of anhydrous acetonitrile. The reaction mixture was heated to reflux (80-81 ° ^C), refluxed with stirring for 30 minutes, cooled to room temperature and stirred for 1 hour.

 The precipitate formed is filtered off, washed with 30 ml of absolute isopropanol and dried to constant weight.

29.73 g (92.3%) of 99.5% 1-phenyl-1-n-nitrobenzoylamino-5-N, N-diethylaminopentane (I) hydrochloride or 29.58 g (91.9%) are obtained in in terms of 100% content of I, counting on 1-phenyl-1-amino-5-N, N-diethylaminopentane. T. pl. 165-167 ^{° C} (from absolute isopropanol).

 II. In anhydrous acetone.

 To 20 g of 90% or 18 g (0.0768 mol) of 100% 1-phenyl-1-amino-5-N, N-diethylaminopentane is added 20 ml of anhydrous acetone, stirred for 10 min at room temperature and at the same time 16.63 g of 90% or 14.97 g (0.0807 mol) of 100% n-nitrobenzoyl chloride are added at a temperature. At the end of the loading of n-nitrobenzoyl chloride, the reaction mass was stirred for 2 hours at room temperature. The precipitate formed is filtered off, washed with 30 ml of absolute isopropanol and dried to constant weight.

28.54 g (88.6%) of 99.5% 1-phenyl-1-n-nitrobenzoylamino-5-N, N-diethylaminopentane (I) hydrochloride are obtained or 28.4 g (88.2%) in in terms of 100% content of I, counting on 1-phenyl-1-amino-5-N, N-diethylaminopentane. Mp 165-167 ^about S.

 III. In an aromatic hydrocarbon environment.

To a solution of 20 g of 90% or 18 g (0.0768 mol) of 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII) in 40 ml of benzene, a solution of 16.78 g was added dropwise with stirring at room temperature. 90% or 15.10 g (0.0814 mol) of 100% n-nitrobenzoyl chloride in 60 ml of benzene. The reaction mass is heated to boiling (80 ^about C), boiled with stirring for 3 hours and cooled to room temperature. The precipitate formed is filtered off.

23.93 g (74.3%) of 98.8% 1-phenyl-1-n-nitrobenzoylamino-5-N, N-diethylaminopentane (I) hydrochloride are obtained, or 23.64 g (73.4%) in in terms of 100% content of I, counting on VII. Mp 165-167 ^{° C} (from absolute isopropanol).

 IV. In an environment of ethyl acetate.

 Similarly to the previous paragraph VIII, the reaction is carried out in a solution of ethyl acetate at the boiling point of the solvent.

25.53 g (79.3%) of 92.2% 1-phenyl-1-n-nitrobenzoylamino-5-N, N-diethylaminopentane (I) hydrochloride are obtained or 23.54 g (73.1%) in in terms of 100% content of I, counting on VII, so pl. 165-167 ^{° C} (from absolute isopropanol).

 The data of elemental analysis of synthesized compound I correspond to the calculated ones.

 PRI me R 2. Obtaining 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII).

 Stage I. Obtaining 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane (III).

To 121 g of 96% (116.16 g (0.358 mol) of 100%) 1-phenyl-1-cyan-1-carbethoxy-5-bromopentane (II) was added 112 ml (79.8 g) 98, 4% (78.55 g (1.074 mol) of 100%) of diethylamine was heated to reflux (62-65 ^{° C)} and kept under stirring for 2 hours while the reaction mass temperature increased to 75 ^C. to the reaction mixture 60 ml of toluene are added, stirred and cooled to room temperature. The precipitated diethylamine bromide hydrate was filtered off, washed with toluene (2x20 ml). The filtrate was evaporated. The residue is obtained in the form of an oily tan liquid in an amount of 115 g with a 94.5% content of 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane (III) or 108.67 g (95 , 9%) in terms of the 100% content of the main substance III, counting on II.

 Stage II. Preparation of 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV).

 1. Using sodium ethylate.

To 150 ml of absolute ethanol, 3.31 g (0.1439 g-a) of sodium metal are added in portions with stirring. A solution of 25.49 g (0.0805 mol) of 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane in 25 ml of absolute ethanol is added to the resulting solution of sodium ethylate. The reaction mass is heated to boiling (78-80 ^about C) and kept at boiling and stirring for 4 hours. Evaporated. 100 ml of water was added to the residue and extracted with toluene (ether) (3x100 ml). The toluene solution is dried over a desiccant, for example, anhydrous magnesium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of toluene. The toluene is evaporated. The residue was distilled in vacuo. Collect the fraction with so Kip. 150-160 ^about With 1 mm RT.article in the form of an oily yellow liquid.

 Obtain 17.59 g (89.33%) of 95.96% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV) or 16.88 g (88%) in terms of 100% - total content IV, counting on III.

 2. Using alkali metal chloride (NaCl) in aqueous dimethyl sulfoxide (DMSO).

To 300 ml of DMSO, 20 ml of water, 5.15 g (0.088 mol) of sodium chloride and 27.75 g (0.088 mol) of 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane ( III). The mixture is heated to boiling (146-147 ^about C) and boiled for 2 hours

The reaction mass is mixed with water and extracted with toluene (2x200 ml). The toluene solution is dried over anhydrous magnesium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of toluene. The toluene is evaporated. The residue was distilled in vacuo. Collect the fraction with so Kip. 150-160 ^about With 1 mm RT.article in the form of an oily yellow liquid.

 Obtain 17.35 g (80.96%) of 95.46% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV) or 16.56 g (77.3%) in terms of 100 % IV, counting on III.

 3. Using an interphase catalyst triethylbenzylammonium chloride (TEBAH) and an aqueous solution of alkali.

20 g (0.3564 mol) of potassium hydroxide or 20 g (0.5 mol) of sodium hydroxide are dissolved in 30 ml of water with stirring. To the resulting solution at 25-46 ^{° C} with stirring was added 0.34 g (0.0015 mol) TEBAHa and 34.03 g of 93% strength or 31.65 g (0.1 mol) of 100% 1-phenyl -1-cyan-1-carbethoxy-5-N, N-diethylaminopentane (III). The reaction mass was maintained at 45-50 ^{° C} and stirring for 1 hour, then added 67 ml of toluene, stirred for 2-3 min, poured 50 ml of water and cooled to room temperature. The mixture was extracted with toluene (2x30 ml). The combined toluene extracts are washed with water (2x50 ml) to pH 7-8, dried over a desiccant, for example, anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of toluene. The toluene is evaporated. The residue was distilled in vacuo. Collect the fraction with so Kip. 150-160 ^about With 1 mm RT.article in the form of an oily yellow liquid.

 Obtain 21.71 g (88.8%) of 99.4% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV) or 21.58 g (88.3%) in terms of 100 % IV, counting on III.

 4. Using an interphase catalyst triethylbenzylammonium chloride (TEBAH), an aqueous solution of alkali in an aromatic hydrocarbon medium.

a) 20 g (0.3564 mol) of potassium hydroxide or 20 g (0.5 mol) of sodium hydroxide are dissolved in 20 ml of water with stirring. To the resulting solution of alkali at 25-45 ^{° C} and with stirring was added 0.34 g (0.0015 mol) TEBAHa solution and 33.67 g of 94% strength or 31.65 g (0.1 mol) of 100% 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane (III) in 33 ml of toluene. The reaction mass was maintained at 45-50 ^{° C} and stirring for 1 hour, poured in 40 ml water and cooled to room temperature.

The mixture was extracted with toluene (2x20 ml). The combined toluene extracts are washed with water (2x50 ml) to a pH of 7-8 and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of toluene. Evaporate. The residue was distilled in vacuo. Collect the fraction with so Kip. 150-160 ^about With 1 mm RT.article in the form of an oily yellow liquid.

 Obtain 21.53 g (88.1%) of 97.54% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV) or 21.0 g (85.93%) in terms of 100% content IV, counting on III.

b) 10 g (0.1782 mol) of potassium hydroxide or 10 g (0.2500 mol) of sodium hydroxide are dissolved in 10 ml of water with stirring. To the resulting solution of alkali at 25-45 ^{° C} and with stirring was added 0.17 g (0.0007 mol) TEBAHa solution and 16.66 g of 95% or 15.83 g (0.0500 mol) of 100% 1-phenyl-1-cyan-carbethoxy-5-N, N-diethylaminopentane (III) in 17 ml of benzene. The reaction mixture was kept at 45-50 ^{° C} and stirring for 1 hour, poured in 35 ml water and cooled to room temperature. Then the reaction mass is treated similarly to 4a.

 Obtain 10.76 g (88%) of 91% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV) or 9.79 g (80%) in terms of 100% IV, counting on III.

 Stage III. Preparation of 1-phenyl-1-carbamido-5-N, N-diethylaminopentane (V).

 1. In the presence of hydrochloric acid.

A solution of 13.4 g (0.0511 mole) of 1-phenyl-1-cyano-5-N, N-dietilaminopentana (IV) in 70 ml of concentrated hydrochloric acid was stirred and heated ^to 50 ° C and held ^at 50 ° C for 4 hours The reaction mass is cooled to room temperature, poured into 100 g of ice and 40% NaOH is added to pH 10.0. The alkaline solution is extracted with toluene (3x50 ml), the toluene extract is washed with 100 ml of water and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of toluene. Evaporate. The residue is crystallized in hexane. The precipitate was filtered off, washed with hexane, and dried in air.

Obtain 9.5 g (66%) of 99.76% 1-phenyl-1-urea-5-N, N-diethylaminopentane (V) or 9.48 g (65.9%) in terms of 100% content V, counting on IV. Mp 70-73 ^C (from hexane).

IR spectrum, ν, cm ^-1 : 3370, 3160 (NH ₂ ), 1640, 1490 (CO, CH CH arom, CH ₂ ).

 2. In the presence of sulfuric acid.

To 6 g of 97.2% strength and 5.83 g (0.0239 mol) of 100% 1-phenyl-1-cyano-5-N, N-dietilaminopentana (IV) under cooling (0 ° ^C, ice ) while stirring, 10.9 ml of concentrated sulfuric acid are added dropwise. The reaction mass is heated to 45 ^about C and kept with stirring and 45 ^about 5 hours

 The reaction mixture was cooled to room temperature, poured into 50 g of ice, made basic with sodium hydroxide solution to pH 10-11. The alkaline solution is extracted with toluene (3x50 ml), the toluene extract is washed with water to pH 9 and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 30 ml of toluene. Evaporate. The residue is crystallized in hexane. The precipitate was filtered off, washed with hexane, and dried.

 Get 3.89 g (62%) of 97.3% 1-phenyl-1-urea-5-N, N-diethylaminopentane (V) or 3.78 g (60%) in terms of 100% - total content of V, counting on IV.

 3. In the presence of alkali in DMSO medium.

a). To 74.55 g of 99.4% or 74.10 g (0.3032 mol) of 100% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV), 9.3 g ( 0.1654 mol) of potassium hydroxide in 400 ml of dimethyl sulfoxide (DMSO) with stirring and cooling (5-10 ^about C) dropwise 80 ml of 30% hydrogen peroxide. Wherein the reaction mass temperature does not exceed 30 ^C. The reaction mixture was kept under stirring at room temperature for 1 h. Monitoring of the reaction by TLC. At the end of the reaction, 530 ml of water are added and extracted with toluene (3x400 ml). The combined toluene extracts were washed with 270 ml of water and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 200 ml of toluene. Evaporate. The residue is crystallized in hexane. The precipitate was filtered off, washed with hexane, and dried.

 Get 60.47 g (76%) of 98% 1-phenyl-1-urea-5-N, N-diethylaminopentane (V) or 59.26 g (74.4%) in terms of 100% - total content of V, counting on IV.

b) Of 14.4 g of 97.3% or 14 g (0.05723 mol) of 100% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV), 2.24 g (0, 0560 mol) of sodium hydroxide, 75 ml of DMSO and 25 ml of 30% H ₂ O ₂ according to the procedure similar to the previous paragraph a), 10.8 g (72%) of 93% 1-phenyl-1-carbamido-5 are obtained -N, N-diethylaminopentane (V) or 10.04 g (66.8%), calculated on the basis of the 100% content of V, counting on IV.

 4. In the presence of potassium tert-butylate.

To a solution of 2.28 g of 86.6% or 1.97 g (0.0081 mol) of 100% 1-phenyl-1-cyan-5-N, N-diethylaminopentane (IV) in 25 ml of tert- with butyl alcohol, 2.12 g (0.0378 mol) of ground potassium hydroxide are added with stirring. The reaction mass is heated to 83 ^° C and boiled for 7 hours. The reaction is monitored by TLC.

 The reaction mixture was poured into 50 g of ice, extracted with toluene (3x30 ml), washed with saturated sodium chloride solution (1x50 ml), dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 25 ml of toluene. Evaporate. The residue is crystallized in hexane. The precipitate was filtered off, washed with hexane, and dried.

 Obtain 1.3 g (61%) of 98.5% 1-phenyl-1-urea-5-N, N-diethylaminopentane (V) or 1.28 g (60.4%) in terms of 100% - total content of V, counting on IV.

 Stage IV. Preparation of 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane (VI).

 1. Using bromine and sodium methylate in methanol.

To a solution of sodium methylate obtained from 300 ml of methanol and 11.85 g (0.5153 g-a) of metallic sodium, a solution of 60.47 g of 98% or 59.26 g (0.2259) is added with stirring at room temperature. mol) of 100% 1-phenyl-1-carbamido-5-N, N-diethylaminopentane (V) in 300 ml of methanol. The reaction mixture was cooled to -1 ^° -0 ^{° C} and slowly (over 1 h) was added dropwise 13 mL (40.42 g) (0.2526 mol) of bromine with vigorous stirring. Then the reaction mass is heated to boiling (65 ^about C) and boiled for 10 minutes The reaction is monitored by TLC.

 The reaction mixture is cooled to room temperature, 1200 ml of water are added, and extracted with toluene (3x600) ml. The combined toluene extract was washed with water (2 x 600 ml) and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 200 ml of toluene. Evaporate.

 Obtain 59.2 g (90%) of 96% 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane (VI) as a pale yellow oily liquid or 56.83 g (86%) in in terms of 100% VI, counting on V.

T.kip. 133 ^about With at 0,025 ml RT.article

 2. Using bromosuccinimide, mercury acetate in a mixture of DMF-methanol.

To a mixture of 5.0 g (0.0191 mol) of 1-phenyl-1-urea-5-N, N-diethylaminopentane (V), 5.85 g (0.0200 mol) of mercury (II) acetate in 80 ml of DMF and 35 ml of methanol with stirring at room temperature, 3.65 g (0.0200 mol) of bromosuccinimide in 25 ml of DMF are added. The reaction mixture was stirred at room temperature (20-25 ° ^C) for 6 hours.

 The precipitate is filtered off, washed with 10 ml of DMF, the filtrate is evaporated over 2/3 of the volume, 100 ml of ethyl acetate and 100 ml of a 0.5% aqueous soda solution are added. The organic layer was separated, the aqueous layer was extracted with ethyl acetate (2 x 100 ml). The combined organic extract was washed with 100 ml of water, dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of ethyl acetate. Evaporate.

 4.5 g (80.7%) of 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane (VI) are obtained, counting by V.

 Stage V. Obtaining 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII).

 1. Using ethanol and alkali.

 A mixture of 12.0 g (0.3000 mol) of sodium hydroxide, 20 ml of water, 20 ml of ethanol, 8.2 g (0.0280 mol) of 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane (VI) boil with stirring for 24 hours

 The reaction mass is cooled to room temperature, poured into 400 ml of water, 100 ml of toluene are added and stirred. The organic layer was separated, the aqueous layer was extracted with toluene (2x100 ml). The combined toluene extract was washed with water (2 x 100 ml) and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of toluene. Evaporate.

6.4 g (97.4%) of 80% 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII) are obtained as a pale yellow oily liquid or 5.12 g (77.9 %) in terms of 100% content of VII, counting on VI. Upon distillation in vacuo of the obtained diamine VII (bp. 117 ^o / 0.022 mm Hg), 5.2 g (79.1%) of 92% VII are obtained in the form of a colorless oily liquid, counting on VI.

 2. Using ethanol, alkali and TEBAH.

 A mixture of 77.72 g (1.9430 mol) of sodium hydroxide, 3.7 g (0.0162 mol) of TEBAH, 78 ml of water, 78 ml of ethanol, 59.2 g of 96% or 56.83 g (0, 1943 mol) 100% 1-phenyl-1-carbomethoxyamino-5-N, N-diethylamino-pentane (VI) is boiled under stirring for 6 hours. The reaction is monitored by GLC.

 The reaction mass is cooled to room temperature, poured into 2800 ml of water, 700 ml of toluene are added and stirred. The organic layer was separated, the aqueous layer was extracted with toluene (2 x 700 ml). The combined toluene extracts were washed with water (2 x 700 ml) and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 300 ml of toluene. Evaporate.

44.4 g (97.5%) of 80% 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII) are obtained as a pale yellow oily liquid or 35.52 g (78%) in in terms of 100% content of VII, counting on VI. T. bale. 117 ^about With at 0,022 mm RT. Art.

 3. Using n-butanol and alkali.

 A mixture of 7.6 g (0.1900 mol) of sodium hydroxide, 100 ml of n-butanol, 10 ml of water and 5.5 g (0.0188 mol) of 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane ( VI) dropping with stirring for 6 hours

 The reaction mixture was cooled to room temperature, poured into 50 ml of water, the organic layer was separated, the aqueous layer was extracted with n-butanol (2 x 50 ml). n-Butanol is distilled off, the residue is treated with 100 ml of toluene and dry over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 50 ml of toluene. Evaporate.

 4.1 g (93.2%) of 76% 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII) are obtained as a pale yellow oily liquid or 3.12 g (71%) in in terms of 100% content of VII, counting on VI.

 4. Using n-butanol, alkali and TEBAH.

 A mixture of 7.6 g (0.1900 mol) of sodium hydroxide, 0.5 g (0.0022 mol) of TEBAH, 15 ml of water, 15 ml of n-butanol and 5.5 g (0.0188 mol) of 1-phenyl- 1-carbomethoxyamino-5-N, N-diethylaminopentane (VI) is boiled under stirring for 4 hours.

 The reaction mass is cooled to room temperature, poured into 50 ml of water, 30 ml of toluene are added and stirred. The organic layer was separated, the aqueous was extracted with toluene (2x30 ml). The combined toluene extract was washed with water (2x30 ml) and dried over anhydrous sodium sulfate. The inorganic precipitate is filtered off, washed with 30 ml of toluene. Evaporate.

 4.05 g (92%) of 78% 1-phenyl-1-amino-5-N, N-diethylaminopentane (VII) are obtained as a pale yellow oily liquid or 3.08 g (70%), calculated 100% content of VII, counting on VI.

 The data of elemental analysis of the synthesized compounds correspond to the calculated ones.

 PRI me R 3. Obtaining 1-phenyl-1-cyan-1-carbethoxy-5-bromopentane (II).

To 100 ml of toluene, under vigorous stirring, 10 g (0.4350 g-a) sodium and heated to a temperature (95 ± 5) ^{° C} for crushing metallic sodium. Then the mixture was slowly added dropwise 25 ml of toluene and 50 ml of absolute ethanol and maintained at reflux (95 ± 5) ^{° C} 40-60 minutes until gas evolution ceased. The reaction mixture was cooled to (55 ± 5) ^{° C,} is added dropwise 54.89 ml (53.52 g), a 99%, or 52.98 g (0.4485 mol) of 100% of diethyl carbonate and 52.95 ml (51 47 g) of 99% or 50.96 g (0.4350 mol) of 100% benzyl cyanide, heated to boiling and the azeotropic mixture of toluene and ethanol was distilled off at atmospheric pressure. When the temperature in the bath gradually as the distillation temperature in the stripping vapor is increased from 78 to 103 ° ^C.

For complete removal of ethanol from the reaction mixture after precipitation and at 95-100 ^{° C} in the vapor further added dropwise 45 ml of toluene.

The reaction mixture was cooled to 10-15 ^C. The precipitate was filtered off and washed with toluene (2x25 ml) and dried. The reaction for the preparation of 1-phenyl-1-cyan-1-carbethoxy-5-bromopentane (II) can also be carried out without isolating the sodium salt of phenylcyanoacetic acid ethyl ester.

89 g (96.9% based on benzyl cyanide) of the sodium salt of phenylcyanoacetic acid ethyl ester are obtained, mp. 221-225 ^C. (dec.).

Further, a mixture consisting of 87 g (0.4119 mol) of the obtained sodium salt of phenylcyanoacetic acid ethyl ester, 464 g (256.64 ml) of 95.86% or 444.79 g (2.0600 mol) of 100% 1,4-dibromobutane and 250 ml of acetonitrile was stirred for 1.5 hours at room temperature, then heated to 45-50 ^{° C} and kept at this temperature for 1 hour and cooled to 15-20 ^C. The precipitated sodium bromide was filtered off, washed with acetonitrile (2x25 ml). Acetonitrile, 1,4-dibromobutane is distilled off from the mother liquor.

 123 g (92.1%) of 97% 1-phenyl-1-cyan-1-carbethoxy-5-bromopentane (II) are obtained in the form of a yellow oily liquid or 119.31 g (89.3%) in terms of 100% content of II, counting on the sodium salt of phenylacetic acid ethyl ester.

T.kip. 135 ^about With at 0,025 mm RT.article

 The data of elemental analysis of synthesized compound II correspond to the calculated ones.

Claims (10)

1. METHOD FOR PRODUCING 1-PHENYL-1-P-NITROBENZOYL-AMINO-5-N, N-DIETHYLAMINOPENTANE AND 1-Phenyl-1-AMINO-5-N, N-DIETHYLAMINOPENTANE HYDROCHLOR, characterized in that p-nitol an anhydrous aprotic solvent is reacted with 1-phenyl-1-amino-5-N, N-diethylaminopentane obtained by reacting 1-phenyl-1-cyan-1-carbethoxy-5-bromopentane with diethylamine by boiling, saponification and decarboxylation of the resulting 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane followed by acid or alkaline hydrolysis to form curing 1-phenyl-1-cyan-5-N, N-diethylaminopentane by treating the obtained 1-phenyl-1-carbamido-5-N, N-diethylaminopentane or bromine in methanol in the presence of sodium methylate at a temperature of from -1 ^o С to the boiling point of the reaction mixture, or bromosuccinimide in the presence of mercury acetate in a mixture of dimethylformamide and methanol and boiling the obtained 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane in an alcohol-alkaline medium. 2. The method according to p. 1, characterized in that the process of condensation of p-nitrobenzoyl chloride with 1-phenyl-1-amino-5-N, N-diethyl aminopentane is carried out in the temperature range from 0 ^o C to the boiling point of the reaction mixture.  3. The method according to claim 1, characterized in that an anhydrous aprotic solvent is an aromatic hydrocarbon, ether, ketone or nitrile.  4. The method according to claim 1, characterized in that acetonitrile is used as an anhydrous aprotic solvent. 5. A method of producing 1-phenyl-1-amino-5-N, N-diethylaminopentane, characterized in that 1-phenyl-1-cyan-1-carbethoxy-5-bromopentane is reacted with diethylamine during smoking, followed by saponification and decarboxylation obtained 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane, by acid or alkaline hydrolysis of the resulting 1-phenyl-1-cyan-5-N, N-diethylaminopentane, by treatment of the obtained 1-phenyl-1- urea-5-N, N-diethylaminopentane or bromine in methanol in the presence of sodium methylate at a temperature of from -1 ^o C to a temperature of boiling the reaction mixture, or bromosuccinimide in the presence of mercury acetate in a mixture of dimethylformamide and methanol and boiling the obtained 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane in an alcohol-alkaline medium. 6. The method according to claim 5, characterized in that the saponification and decarboxylation of 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane is carried out with an aqueous solution of caustic alkali in the presence of an interfacial catalyst such as triethylbenzylammonium chloride, at a temperature from room temperature to 50 ^o C.  7. The method according to claims 1 and 6, characterized in that the saponification and decarboxylation of 1-phenyl-1-cyan-1-carbethoxy-5-N, N-diethylaminopentane is carried out in an aromatic hydrocarbon medium. 8. The method according to claim 1, characterized in that the acid hydrolysis of 1-phenyl-1-cyan-5-N, N-diethylaminopentane is carried out in the presence of hydrochloric acid at a temperature of from room temperature to 50 ^o C or in the presence of sulfuric acid at 0 50 ^o C. 9. The method according to claim 1, characterized in that the alkaline hydrolysis of 1-phenyl-1-cyan-5-N, N-diethylaminopentane is carried out in the presence of alkali and hydrogen peroxide in dimethyl sulfoxide at a temperature of from 5 ^o C to room or in the presence of boiling potassium tert-butylate.  10. The method according to claim 1, characterized in that the boiling of 1-phenyl-1-carbomethoxyamino-5-N, N-diethylaminopentane in an alcohol-alkaline medium is carried out in the presence of an interfacial catalyst such as triethylbenzylammonium chloride.