VU, TRUC CHI,BRZOZOWSKI, DAVID B.,HANSON, RONALD L.,KOLOTUCHIN, SERGEI V.,MAZZULLO, JOHN A. JR.,WANG, JIANJI,WONG, KWOK,YU, JURONG,ZHU, JASON
申请号：
ES12162624
公开号：
ES2494793T3
申请日:
2003.12.04
申请国别(地区):
ES
年份:
2014
代理人:
摘要：
A method of producing a dipeptidyl peptidase IV inhibitor based on cyclopropyl fused pyrrolidine, comprising: (a) protecting the acid (αS) -α-amino-3-hydroxytricyclo [3.3.1.13.7] decane-1-acetic acid with BLOC； (b) coupling the (αS) -α - [[(1,1-dimethylethoxy) carbonyl] amino] -3-hydroxytricyclo [3.3.1.13.7] decane-1-acetic acid or its 1,4-diazabicyclooctane salt with ( 1S, 3S, 5S) -2-azabicyclo [3.1.0] hexane-3-carboxamide to produce the 1,1-dimethyl ester of 3- (aminocarbonyl) - (αS) -α- (3-hydroxytricyclo [3.3. 1.13.7] dec-1-yl-ß-oxo- (1S, 3S, 5S) -2-azabicyclo [3.1.0] hexane-2-ethanolamine； (c) dehydrate the 1,1-dimethyl ester of the acid 3- (aminocarbonyl) - (αS) -α- (3-hydroxytricyclo [3.3.1.13.7] dec-1-yl-β-oxo- (1S, 3S, 5S) -2-azabicyclo [3.1.0] hexane -2 ethanecarbamic to produce 1,1-dimethyl ester of 3- (cyano) - (αS) -α- (3-hydroxytricyclo [3.3.1.13.7] dec-1-yl-β-oxo- (1S, 3S, 5S) -2-azabicyclo [3.1.0] hexane-2 ethanecarbamic acid, and (d) hydrolyze the 1,1-dimethyl ester of 3- (cyano) - (αS) -α- (3-hydroxytricyclo [3.3] .1.13.7] dec-1-yl-β-oxo- (1S, 3S, 5S) -2-azabicyclo [3.1.0] hexane-2-ethanecarbamine to form the dipeptidyl peptidase IV inhibitorUn procedimiento de producción de un inhibidor de dipeptidil peptidasa IV basado en pirrolidina fusionada a ciclopropilo, que comprende: (a) proteger el ácido (&alpha；S)-&alpha；-amino-3-hidroxitriciclo[3.3.1.13,7]decano-1-acético con BLOC ； (b) acoplar el ácido (&alpha；S)-&alpha；-[[(1,1dimetiletoxi)cabonil]amino]-3-hidroxitriciclo[3.3.1.13,7]decano-1-acético o su sal de 1,4-diazabiciclooctano con (1S,3S,5S)-2-azabiciclo[3.1.0]hexano-3-carboxamida para producir el 1,1-dimetil éster del ácido 3-(aminocarbonil)-(&alpha；S)-&alpha；-(3-hidroxitriciclo[3.3.1.13,7]dec-1-il-ß-oxo-(1S,3S,5S)-2-azabiciclo[3.1.0]hexano-2-etanoc arbámico； (c) deshidratar el 1,1-dimetil éster del ácido 3-(aminocarbonil)-(&alpha；S)-&alpha；-(3-hidroxitriciclo[3.3.1.13,7]dec-1-il-ß-oxo-(1S,3S,5S)-2-azabiciclo[3.1.0]hexano-2 etanocarbámico para
