CAJ | 학술논문

乌拉地尔是一种新型的多靶点降压药物,现对其已有的合成方法进行改进.讨论了相转移催化条件和逆向相转移催化条件下,以6-(3-氯丙基)氨基-1,3-二甲基尿嘧啶和1-(2-甲氧基苯基)哌嗪盐酸盐为原料,进行乌拉地尔合成的反应结果.逆向相转移催化条件下所获收率高于相转移催化条件.当选择β-CD为逆向相转移催化剂,水为溶剂,反应温度为95℃,在1500 r?min?1转速下经2~3 h反应,可以大于80%的收率获得含量为96.6%~98.0%乌拉地尔粗品.乌拉地尔粗品精制采用反溶剂重结晶法,其适宜条件是7℃时,二氯甲烷为溶剂,丙酮为反溶剂,所获得乌拉地尔成品含量>98.5%,收率>95%.乌拉地尔结构经1H-NMR、MS、IR和元素分析确证.与已有工艺比较,改进的合成方法具有显著缩短反应时间,产物分离简单易行,合成工艺简单、易于工业化生产等优点.
오랍지이시일충신형적다파점강압약물,현대기이유적합성방법진행개진.토론료상전이최화조건화역향상전이최화조건하,이6-(3-록병기)안기-1,3-이갑기뇨밀정화1-(2-갑양기분기)고진염산염위원료,진행오랍지이합성적반응결과.역향상전이최화조건하소획수솔고우상전이최화조건.당선택β-CD위역향상전이최화제,수위용제,반응온도위95℃,재1500 r?min?1전속하경2~3 h반응,가이대우80%적수솔획득함량위96.6%~98.0%오랍지이조품.오랍지이조품정제채용반용제중결정법,기괄의조건시7℃시,이록갑완위용제,병동위반용제,소획득오랍지이성품함량>98.5%,수솔>95%.오랍지이결구경1H-NMR、MS、IR화원소분석학증.여이유공예비교,개진적합성방법구유현저축단반응시간,산물분리간단역행,합성공예간단、역우공업화생산등우점.
Urapidil is a new class antihypertensive drug with multiple targeted activities. An improved synthetic method of it was described. The reaction results of the synthesis of Urapidil under phase-transfer catalysis and inverse phase-transfer catalysis were discussed when 6-[(3-chloropropyl) amino]-1,3-dimethyluracil and 1-(2-methoxy phenyl) piperazine was chosen as the raw materials. The yields of inverse phase-transfer catalysis are higher than that of phase-transfer catalysis. Whenβ-Cyclodextrin was used as an inverse phase-transfer catalyst, over 80% isolated yield of Urapidil with 96.6%~98.0% purity was obtained after 2~3 h reaction in aqueous media at 95℃ with an agitation rate of 1500 r?min?1. Urapidil was purified by anti-solvent precipitation. Under the appropriate condition which dichloromethane was used as the solvent and acetone was used as the anti-solvent at 7℃, Urapidil was got with>98.5%purity and>95%yield. The structure of objective product was confirmed by 1H-NMR, IR, MS and elemental analysis. Comparing with the current technology, this described synthetic method has the merits of the greatly shorten the reaction time, the easy purification of the products, and its synthetic technology is simple and convenient to be used for industrial application.