PROCESS FOR THE PREPARATION OF N-[(1-NBUTYL-4-PIPERIDYL)METHYL]-3,4-DIHYDRO-2H-[1,3]OXAZINO[3,2-A]INDOLE-10-CARBOXAMIDE AND SALTS AND INTERMEDIATES IN THE PROCESS

摘要

Process for the production of N-[(1-n-butyl-4-piperidyl) methyl]-3,4- dihydro-2H-[1,3] -oxazino[3,2-a] -indole-10 carboxamide (SB 207266) (I) involves reaction of N-(1-n-butyl-4-piperidyl)methylamine (II) with an oxazino-indole carboxylate of formula (III). R = alkyl. The reaction is catalysed by an aluminium or lithium-based catalyst, preferably trimethylaluminium. A mixture of (II) and (III) is treated with a solution of trimethylaluminium in toluene or hexanes at room temperature and then refluxed for ca. 4 hours. #CMT#USE : #/CMT# (I) is an 5-HT4 receptor antagonist under development as a treatment for irritable bowel syndrome. #CMT#ADVANTAGE : #/CMT# This synthesis uses the expensive intermediate (II) at a later stage in the process, leading to higher yields and greater commercial applicability than the prior-art method.