Patent ID: 6136982
Filing Date: 2000-10-24
Classification: C07D

Abstract:
A method for making 3-amino-2-chloro-4-methylpyridine comprising the following steps:(a) reacting ethylcyanoacetate with acetone to yield ethylisopropylidenecyanoacetate;(b) reacting the ethylisopropylidenecyanoacetate so produced with N.N-dimethylformamide dimethyl acetal to yield ethyl 2-cyano-5-(N,N-dimethylamino)-3-methyl-2,4-pentadienoate;(c) treating the ethyl 2-cyano-5-(N,N-dimethylamino)-3-methyl-2,4-pentadienoate so produced with hydrogen chloride in ethanol, to effect ring closure, thus producing ethyl 2-chloro-4-methylnicotinate;(d) hydrolyzing the ethyl 2-chloro-4-methylnicotinate so produced to yield 2-chloro-4-methylnicotinic acid;(e) reacting the 2-chloro-4-methylnicotinic acid so produced with thionyl chloride to yield the corresponding acid chloride;(f) treating the acid chloride so produced with anhydrous ammonia in ethanol, to yield 2-chloro-4-methyl-3-carboxamide; and,(g) converting the 2-chloro-4-methyl-3-carboxamide so produced, via the Hofmann reaction (treatment with solution of chlorine or bromine in excess sodium hydroxide), to 3-amino-2-chloro-4-methylpyridine.