本文選題：MBX- + GPR激動(dòng)藥��； 參考：《中國(guó)醫(yī)藥工業(yè)雜志》2017年04期

【摘要】：4-哌啶甲酰胺(4)經(jīng)氨基保護(hù)得N-叔丁氧羰基哌啶-4-甲酰胺(5),經(jīng)硫代得4-硫代氨甲酰基哌啶-1-甲酸叔丁酯(6),經(jīng)成環(huán)反應(yīng)得4-(4-氯甲基噻唑-2-基)哌啶-1-甲酸叔丁酯(7),再經(jīng)醚化、脫保護(hù)及取代反應(yīng)合成MBX-2982(1)。本研究進(jìn)行如下改進(jìn):制備5時(shí),用碳酸鉀替代4-二甲胺基吡啶(DMAP)使后處理簡(jiǎn)便快速;制備6時(shí),用乙醚作析晶溶劑使收率由72%提高至84.5%;制備7時(shí),減少了2種反應(yīng)試劑(硫酸鎂和碳酸鎂),降低反應(yīng)溫度(由回流降至室溫),反應(yīng)正常進(jìn)行。制備1時(shí),采用鈀催化劑和膦配體偶聯(lián)條件使原料反應(yīng)完全。本研究總收率42%(以4計(jì),文獻(xiàn)總收率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%).
【作者單位】： 江南大學(xué)藥學(xué)院;
【分類號(hào)】：R914.5
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本文編號(hào)：1832472