反应详情

Key building block (E)-2-{4-[2-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-vinyl]-phenyl}-5-chloro-pentanoic acid methyl ester (VIII) can be prepared according to Scheme 7. Starting with commercially available 4-(bromo-phenyl)-acetonitrile (XVI), deprotonation with strong base followed by alkylation using 1-bromo-3-chloropropane gives 2-(4-bromo-phenyl)-5-chloro-pentanenitrile (XXXII). Hydrolysis of XXXII under acidic conditions furnishes 2-(4-bromo-phenyl)-5-chloro-pentanoic acid (XXXIII). Nucleophilic acyl substitution converts XXXIII to 2-(4-bromo-phenyl)-5-chloro-pentanoic acid methyl ester (XXXIV), which undergoes Heck reaction with (2-acryloylamino-phenyl)-carbamic acid tert-butyl ester to give key building block (E)-2-{4-[2-(2-tert-butoxycarbonylamino-phenylcarbamoyl)-vinyl]-phenyl}-5-chloro-pentanoic acid methyl ester (VIII).