PROCESS FOR PREPARING N-(4-PIPERIDINE)BENZ AMIDE AND NOVEL ACTIVE THIOESTER AS AN INTERMEDIATE

摘要

PURPOSE: An N-(4-piperidine) benzamide is prepared by the reaction of thioester and is-piperidine amine derivatives which has gastroenteric irritative physiological activities. CONSTITUTION: Carboxylic derivatives and alkyl chloroformate are reacted to give an intermediate(formula 5), and reacted with 2-mercaptobenzimidazole to give the novel active thioester(formula 3). Active thioester and is-piperidine amine derivatives(formula 2) are reacted to give benzamide derivatives(formula 1; R is C1-C6 lower alkyl; L is an alkyl or aryloxyalkyl). Thus, 376 mg of triethyl amine and 280 mg of ethyl chloroformate are drop in 500 mg of 4-amino-5-chloro-2-methoxybenzoic acid and reacted at 0-10°C for 1.5 hours, adding 396 mg of 2-mercaptobenzimidazole at room temperature for 6 hour. A mixed solution of 630 mg of is-4-amino-3-method-1-£3-(4-fluorophenoxy) propyl|piperidine and 1 ml of N,N-dimethyl form amide is drop at room temperature for 5 hours in the reactant to give 963 mg of is-2-method-4-amino-5-chloro-N-£1-£3-(4- fluorophenoxy)propyl|-3-method-4-piperidinyl|benzamide1 hydrate.