DE1543850A1 - Process for the preparation of 4-amino-5-halogen-2-substituted benzamide derivatives - Google Patents

Description

, Wtrner Koch, Ridhard Glawe: = lfig »Klaus Delfs Il

SOCIETB D'ETUDES SOIEKTIiTQUES ET INDUSTRIELLES DE L'ILE-DE-FRÄHCE, Paris, France

Method for dividing τοπ 4-araino-5-halogen ~ -2-substituted benzamide derivatives

The present invention relates to a method for Production of 4-amino-5-halogen-2-substituted benzamide derivatives, which is characterized in that 4-amino- -5-halogen-2-substituted benzoic acid esters (I) with amines (II) converted to 4-araino-5-jialogen-2-substituted benzamide derivatives.

The method of the present invention can be carried out by the following scheme

O CO OO OO

H ₂ N - Z

(Π)

(III)

BATH ORIGINAL

illustrates where H is an esterified carboxyl group, X is halogen, Y is hydrogen or an alkyl group, and Z represents a tertiary aminoalkyl group.

The starting materials (I) of the present invention are new and are prepared, for example, by esterifying 2-hydroxy (or alkoxy) -4-amino--5-iialo-benzoic acid. This is obtained by hydrolyzing 2 ~ hydroxy-4-acetamido> 5 ~ halogen- 'benaoesüure which vmrde produced by Kolbe reaction of 3' Acütarairio-4 ~ halogenp} iGtiol ocier hydrolyzing 2-alkoxy -4-acetumido ~ 5 ~ 'halogen - benzoic acid alkyl ester, which was obtained from the reaction of the above-mentioned 2 ~ hydroxy ~ 4-acetamido-5-halogen also aaiivtre uit -J) generallyc; / l?! Chv; efelic acid.

The reaction of the present invention is carried out by reacting the starting materials (I) with amines (II). Among the starting materials (I) there are pale substances in benzoic acid, which are bits of a hydroxyl or alkoxy group, such as methoxy, ethoxy, propoxy, butoxy and the like. in 2-position, with an aaiao group *. in 4 digits, and with halogen such as chlorine, bromine and the like in _; 5-position are substituted. Allyl esters are added to the prayers

such as methyl ester, ethyl ester, propyl ester, butyl ester, oyenmethyl ester and the like; Aryl esters such as phenyl esters, ifitropiitnyl ethers and the like; Benaylfcster; Phenethyl ester and the like

909881/1520 ORIGINAL BATHROOM

k. 3 ■ "■

The aryines (II) also mean alkylaruins such as methylamine, ethylamine, propylamine, butylamine, isobutylamine and the like, all of which are substituted with dialkylaraino groups, for example dimethyl amino, diethylranino groups and the like; with a β ringge oblo β where Heat whose both Alkylgrupperi combined in these dialkylamine with Btioketoff- or oxygen atom or not fcombinieri- (concrete examples thereof are pyrrolidyl, piperidyl, Piperadin- _f morpholine, Alkylpiperadino- etc.); or with a tertiary amino group such as N-methylaniline-.

The Auagangesubetanzeti (I) are treated as amines (II) in the presence or absence of an organic solvent such as ether, benzene and the like. At the same time, an excessive amount of the amines (II) as all solvents can also be used. The implementation wire 'usually in the temperature range of 100 to 150 ⁰ C durcJiceiüIirt. but one can also work at a lower or higher temperature = n. The reaction can also be carried out under pressure. in the presence of a condensing agent for an ■ Amid J eru; gsrealction, for example alkali alcohol, allcaliumid and ri.gl ·,;, the reaction can proceed satisfactorily in certain cases. If desired, the product obtained by the above treatment may be collected in the form of an inorganic salt such as hydrochloride phosphate and the like, or an organic acid salt.

909881/1520 BAD OR.G.NAU

The product, the 4 ~ amiiio ~ 5 ~ halogen-2 --- 8 ⁱ substituted benzamide derivatives (III ^ iet ale pharmaceutical, for example as an anti-emetic.

The following example serves to illustrate the invention.

A mixture of 2 "Hetliox ₁ y-4" Rttiiuo - ^ - chlorobonaoic acid methyl ester (1.0 g) and diethylaminoethylamine (2.7 ^) t is refluxed for 10 hours at 110 ⁰ O, under reduced pressure an excess Amount of diethylariiiioüthylaain is distilled off and V / asoer is added to the residue, with calibration crystals

form. The crystals (1. Og) are collected by filtration. U8 Benzene uricriRtallisiert, where pure crystals mp. 144 to 146 ° ^r ; result. - Infrared absorption spectrum:

0 HH MO ", 3330, 3250 cm" ¹ ■ $ CO 1640 cm "" ¹

With application in the public. Using the same procedure as that of the above examples, the following compounds are obtained:

BATH ORIGINAL

909881/1520

Fp * 169 to 171 ⁰ C

Analysis calculated for C ₁₂ H ₁₈ O ₂ N

C 53.04 H 6.64 N 15> 46 Found; C 52.94 H 6.86 N 15.66

Mp. 169 to 170 ⁰ C,

Mp. 198 to 200 ^° C

Analysis calculated for C 1 H ₂₀ Oj NaCl C 53.59 H 6.42 Ii 15.39 Found: C 53.29 H 6.01 N 13.52

Ii-PyrrolidinGätixyl-2-nie1; hoxy ~ 4-aniino-5-ciilor-benzamide Pp _n 175-178 ⁰ C.

~ Patent claim

_BATH

90988 1/1520 "

Claims (1)

Godfather α tan.3 pruch Process for the preparation of "4" amino-5-naiogen-2-substituted Benzamicide derivatives, characterized in that 4-aiaino- "5-halogeii ~ 2-substituted" Benzoic acid of the general formula: in which R is an esterified carboxyl group, X is halogen and Y is hydrogen or an alivyl group, Aninsn raises the general my formula: HpII - 2 » in which Z is a tertiary aminoalicyl group, converts, v / o in itself 4'amino-5 --- halogen-2-'-substituted benzamide derivatives of a general formula: COKH-2
I. 2
in which X ₅ , Y and % have the above meaning. result = .— "-. "BAD ORIGINAL 909881/1520