Patent ID: 6248882
Filing Date: 2001-06-19
Classification: A61P,C07C,C07D

Abstract:
A process for preparing [4S-[4.alpha.(R*),7.alpha.,10a.beta.]]-octahydro-4-[(2-mercapto-1-oxo-3-ph enylpropyl)amino]-5-oxo-7H-pyrido-[2,1-b][1,3]thiazepine-7-carboxylic acid which comprises:a) reacting the compound of the formula ##STR28##with the dioxolane of the formula ##STR29##wherein L is a leaving group to give the compound of the formula ##STR30##b) treating the product of formula III with water under refluxing conditions to give the compound of the formula ##STR31##c) treating the compound of formula IV to exchange the dioxolane acetal with a dimethoxy acetal and convert the carboxylic acid to the methyl ester to give (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester;d) coupling (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester with the N-protected amino acid of the formula ##STR32##wherein P.sub.1 is an amino protecting group and P.sub.2 is a mercapto protecting group to give the dipeptide of the formula ##STR33##e) removing the P.sub.2 mercapto protecting group from the dipeptide of formula VI followed by acid catalyzed cyclization to give the lactam of the formula ##STR34##f) removing the P.sub.1 amino protecting group from the lactam of formula VII followed by coupling with the acylmercaptoalkanoic acid of the formula ##STR35##wherein R.sub.6 is methyl or phenyl to give the compound of the formula ##STR36##g) treating the compound of formula IX to remove the R.sub.6 --C(O)-- group and convert the methyl ester to the carboxylic acid and yield the desired product.