Synthesis of 5-substituted 5-hydroxy-2-pyrrolidones, metabolites of the antipsychotic benzamide remoxipride.
Synthesis of 5-substituted 5-hydroxy-2-pyrrolidones, metabolites of the antipsychotic benzamide remoxipride.
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5-取代的 5-羟基-2-吡咯烷酮的合成，抗精神病药苯甲酰胺瑞莫必利的代谢物。
DOI：
10.3891/acta.chem.scand.43-0476
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
M. Widman
中科院分区：
文献类型：
--
作者：
L. Gawell;C. Hagberg;T. Högberg;M. Widman
本文报道多巴胺D-2拮抗剂雷莫西必利的两种尿代谢产物5-[（3-溴-2，6-二甲氧基苯甲酰胺基）甲基]-5-羟基-2-吡咯烷酮（3）及其1-乙基类似物2 [1，（S）-3-溴-N-[（1-乙基-2-吡咯烷基）甲基]-2，6-二甲氧基苯甲酰胺]的合成。两个合成方案导致一个共同的中间体，5-苯甲酰氨基-4-氧代戊酸4，开发。这一关键中间体允许转化为任一代谢物。4与氯甲酸异丁酯反应得到混合碳酸酐，其经乙胺或氨处理后分别得到4-氧代戊酰胺5和6。闭环得到相应的5-羟基-2-吡咯烷酮2和3。
This paper describes the synthesis of 5-[(3-bromo-2,6-dimethoxybenzamido)-methyl]-5-hydroxy-2-pyrrolidon e (3) and its 1-ethyl analogue 2, two urinary metabolites of the dopamine D-2 antagonist remoxipride [1, (S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2, 6-dimethoxybenzamide]. Two synthetic schemes leading to a common intermediate, 5-benzamido-4-oxopentanoic acid 4, were developed. This key intermediate permits conversion into either metabolite. Reaction of 4 with isobutyl chloroformate furnished a mixed carbonic anhydride, which upon treatment with ethylamine or ammonia gave the 4-oxopentanamides 5 and 6, respectively. Ring-closure afforded the corresponding 5-hydroxy-2-pyrrolidones 2 and 3.