A New and Efficient Synthesis of 6-[(5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic Acid, a Potent LFA-1/ICAM Inhibitor
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- 作者：Huiping Zhang ; Scott H. Watterson ; Zili Xiao ; T. G. Murali Dhar ; Balu Balasubramanian ; Joel C. Barrish ; Bang-Chi Chen
- 刊名：Organic Process Research & Development
- 出版年：2010
- 出版时间：July 16, 2010
- 年：2010
- 卷：14
- 期：4
- 页码：936-938
- 全文大小：160K
- 年卷期：v.14,no.4(July 16, 2010)
- ISSN：1520-586X
文摘
An efficient synthesis of 6-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic acid 1 is described. This new process involves an in situ protection of 6-chloronicotinic acid as trimethylsilyl ester followed by coupling with spirocyclic hydantoin core 2 to give the target product in 89% overall yield after one-pot deprotection and final API recrystallization.