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Process for preparation of Bendamustine
专利权人:
发明人:
申请号:
EP13163191.3
公开号:
EP2690096A1
申请日:
2013.04.10
申请国别(地区):
EP
年份:
2014
代理人:
摘要:
The present invention relates to a method for preparation of alkyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoate (7) from 2-fluoro-5-nitroaniline, comprising the steps of:a) conversion of 2-fluoro-5-nitroaniline to 5-(2-fluoro-5-nitroanilino)-5-oxopentanoic acid (1) using glutaric anhydride, conversion of compound (1) to methylammonium 5-[2-(methylamino)-5-nitroanilino]-5-oxopentanoate (2) using methylamine conversion of compound (2) to 5-[2-(methylamino)-5-nitroanilino]-5-oxopentanoic acid (3) and condensation of compound (3) to 4-(1-methyl-5-nitro-1H-benzimidazol-2-yl)butanoic acid (4),b) esterification of the product (4) of step a) to alkyl 4-(1-methyl-5-nitro1H-benzimidazol-2-yl)butanoate (5),c) reduction of the product of step b) to alkyl 4-(5-amino-1-methyl-1H-benzimidazol-2-yl)butanoate (6), andd) conversion of the product of step c) to alkyl 4-[5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl]butanoate (7).
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