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目的优化半富马酸喹硫平的合成工艺,并严格控制成品质量,为大规模生产奠定基础。方法选用廉价易得的二苯并[b,f][1,4]硫氮杂-11-[10H]酮(2)为起始原料,在催化量三乙胺的作用下,经氯代反应制备11-氯-二苯并[b,f][1,4]硫氮杂艹卓(3);以甲苯为溶剂,3与1-[2-(2-羟基乙氧基)乙基]哌嗪(4)经氨解反应制备喹硫平,再与富马酸成盐即得目标物。工艺优化过程中,对其有关物质谱进行分析、确定,并严格限量。结果与结论三步反应的总收率为79.9%,单个有关物质含量均小于0.1%,有关物质总量均小于0.2%,终产品的滴定含量均高于99.0%,有机溶剂的限量检测满足标准要求。
Objective To optimize the synthetic process of quetiapine hemifumarate and to strictly control the quality of finished products, so as to lay the foundation for large-scale production. Methods Starting from dibenzo [b, f] [1,4] thiazepin-11- [10H] one (2), which is cheap and easy to obtain, under the action of catalytic amount of triethylamine, Reaction of 11-chloro-dibenzo [b, f] [1,4] thiazepine (3) with toluene as solvent and 3- [2- (2- hydroxyethoxy) ] Piperazine (4) Prepared by aminolysis reaction quetiapine, and then with fumarate salt to obtain the target compound. Process optimization process, the relevant material spectrum analysis, determine, and strictly limited. RESULTS AND CONCLUSION The total yield of the three-step reaction was 79.9%. The contents of single related substances were less than 0.1%, the total amount of related substances was less than 0.2%, and the titration of the final product was higher than 99.0%. The limited detection of organic solvents met the standard Claim.