Process development of the synthetic route to r116301

被引：9

作者：

Guillaume, Michel ^{[1
]}

Cuypers, Jef ^{[1
]}

Dingenen, Jul ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2007年 / 11卷 / 06期

关键词：

D O I：

10.1021/op700086d

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

We describe in this paper the synthesis of compound 1 (R116301), which was developed to prepare pilot scale quantities (20-50 kg) of drug substance. The synthesis involves the (BuLi)-Bu-s deprotonation of Boc-protected piperidone acetal 2, followed by benzaldehyde addition and ring closure to cyclic carbamate 4. Piperidine acetal 5 is resolved with Brown's acid and acylated. The ketone obtained after piperidine acetal deprotection undergoes reductive amination with N-benzyl piperazine, the most critical step in the synthesis. After debenzylation, final coupling and salt formation, compound 1 is obtained over 10 steps with 4% overall yield.

引用

页码：1079 / 1086

页数：8

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