A practical and efficient synthesis of the selective neuronal acetylcholine-gated ion channel agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate (SIB-1508Y)

被引：90

作者：

Bleicher, LS ^{[1
]}

Cosford, NDP ^{[1
]}

Herbaut, A ^{[1
]}

McCallum, JS ^{[1
]}

McDonald, IA ^{[1
]}

机构：

[1] SIBA Neurosci Inc, La Jolla, CA 92037 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1998年 / 63卷 / 04期

关键词：

D O I：

10.1021/jo971572d

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An efficient, high-yielding synthetic procedure for the preparation of the novel neuronal acetylcholine-gated ion channel agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate [(S)-2, SIB-1508Y] is described. The key steps in the process include the lithium bis(trimethylsilyl)amide-mediated acylation of N-vinylpyrrolidinone with ethyl 5-bromonicotinate, a high-yielding sodium borohydride reduction of imine 5, and a new heteroaryl-alkyne cross-coupling protocol for the introduction of the ethyne moiety in (S)-2. The preparation of enantiomerically pure (S)-2 was accomplished via a combination of enantioselective reduction of imine 5 and crystallization of enantiomerically enriched 5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine (7) as the dibenzoyl-L-tartaric acid salt.

引用

页码：1109 / 1118

页数：10

共 48 条

[1] OPTICALLY PURE (+)-NICOTINE FROM (+/-)-NICOTINE AND BIOLOGICAL COMPARISONS WITH (-)-NICOTINE [J].