GPR119激动药MBX-2982的合成

发布时间：2018-05-02 05:05

  本文选题：MBX- + GPR激动药　； 参考：《中国医药工业杂志》2017年04期

【摘要】：4-哌啶甲酰胺(4)经氨基保护得N-叔丁氧羰基哌啶-4-甲酰胺(5),经硫代得4-硫代氨甲酰基哌啶-1-甲酸叔丁酯(6),经成环反应得4-(4-氯甲基噻唑-2-基)哌啶-1-甲酸叔丁酯(7),再经醚化、脱保护及取代反应合成MBX-2982(1)。本研究进行如下改进:制备5时,用碳酸钾替代4-二甲胺基吡啶(DMAP)使后处理简便快速;制备6时,用乙醚作析晶溶剂使收率由72%提高至84.5%;制备7时,减少了2种反应试剂(硫酸镁和碳酸镁),降低反应温度(由回流降至室温),反应正常进行。制备1时,采用钯催化剂和膦配体偶联条件使原料反应完全。本研究总收率42%(以4计,文献总收率30.8%)。
[Abstract]:4- piperidine formamide 4) N- tert-butyloxycarbonyl piperidine-4-formamide 5o, 4thioformyl piperidine-1-tert butyl formate 6N, 4-chloromethylthiazole-2-yl) piperidothiazole-2-yl) piperidine-1-butylformate, then etherified by thiothiazolyl 4-chloromethylthiazolyl) piperidothiazolyl) piperido-1-butyl formate. Synthesis of MBX-2982 ~ (2 +) by deprotection and substitution reaction. The following improvements were made in this study: at 5, potassium carbonate was used to replace 4-dimethylaminopyridine (DMAP) to make the post-treatment simple and rapid; at 6, the yield was increased from 72% to 84.5% by using ether as the crystallization solvent, and the yield was increased from 72% to 84.5%. Two kinds of reagents (magnesium sulfate and magnesium carbonate) were reduced and the reaction temperature was lowered (from reflux to room temperature). At 1, the reaction of the raw material was completed by coupling the PD catalyst with the phosphine ligand. The total yield of this study was 42% (in 4 cases, the total yield of literature was 30.8%).
【作者单位】： 江南大学药学院;
【分类号】：R914.5
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本文编号：1832472