CAS: 1433875-21-8; 5-(4-Bromophenyl)-6-(2-((5-Bromopyrimidin-2-yl)Oxy)Ethoxy)Pyrimidin-4-Amine

上下游产品

2-(4-bromophenyl)-acetic acid 5-(4-bromophenyl)-4,6-dichloropyrimidine (4-bromo-phenyl)-acetic acid methyl ester 2-(4-bromophenyl)-malonic acid dimethyl ester

4-溴苯乙酸甲酯置于盐酸,Lithium Amide,Sodium Methylate,Lithium Tert-Butoxide,三氯氧磷体系中,用 四氢呋喃,甲醇,水,二甲基亚砜,N,N-二甲基甲酰胺 用作溶剂,化学反应 21.0H,反应生成马西替坦杂质
参考文献:通过锂酰胺介导的亲核取代反应合成内皮素受体拮抗剂macitentan的改进的单锅法
标题:通过锂酰胺介导的亲核取代反应合成内皮素受体拮抗剂macitentan的改进的单锅法
摘要:摘要描述了从5-(4-溴苯基)-4,6-二氯嘧啶开始的内皮素受体拮抗剂macitentan的改进,简单,有效和可伸缩合成,总收率约为62%. 图形概要
Doi:10.1007/s00706-017-2098-2

专利信息

专利号:WO-2025102245-A1
优先权日:2023-11-14
标题:Synthesis method for dual endothelin receptor antagonist aprocitentan
发明人：XU XIANGUANG; WANG ZHEN; ZHU GUORONG; TU YONGJUN
权利人:ZHEJIANG TIANYU PHARMACEUTICAL CO LTD
摘要:Provided in the present invention is a synthesis method for aprocitentan, comprising the following steps: 1) a compound of formula X and a sulfonylation reagent compound of formula XI undergoing a sulfonylation reaction to prepare a compound of formula XII; and 2) removing an R protective group on the pyrimidine sulfonamide compound of formula XII obtained in the previous step, so as to obtain aprocitentan. The synthesis method of the present invention overcomes the problem in the prior art that preparing macitentan by means of condensation of chloropyrimidine and sulfonamide needs to use an excessive amount of a strong base and involves a relatively low conversion efficiency, relatively many side products and other defects. The synthesis method does not need using a fluorine reagent for fluorination, involves economical steps, is environmentally-friendly, and has a relatively low comprehensive production cost. Compared with existing methods for preparing aprocitentan, the method of the present invention has characteristics of easily available raw materials, being environmentally-friendly and economical, and the like, thereby facilitating the industrial production of aprocitentan.

专利号:US-11667610-B2
优先权日:2016-09-28
标题:Method for preparing Macitentan and intermediate compound thereof
发明人：JIA QIANG; MA CHI; YANG ZHENGWEI; YANG JINJIN
权利人:SEASONS BIOTECHNOLOGY TAIZHOU CO LTD
摘要:The present invention relates to technical field of chemical synthesis of drugs, and provides a preparation method of Macitentan and intermediate compound thereof. Adding THF solution containing compound II and 5-bromo-2-chloropyrimidine slowly into THF solution containing base to react, or adding THF solution containing compound II and THF solution containing 5-bromo-2-chloropyrimidine slowly at the same time into THF solution containing base to react and obtain Macitentan (shown as compound I), wherein the base is selected from sodium hydride, potassium hydride, lithium hydride or lithium bis(trimethylsilyl)amide. The selectivity of the preparation method is very good, which is suitable for industrial production. The obtained product Macitentan has good quality and high yield. And the product compound II also has good quality and high yield, its HPLC purity is up to 99.0%, the content of impurity A is less than 0.20%, the content of impurity B is less than 0.25%.

专利号:CN-117736152-A
优先权日:2023-11-14
标题 :Synthesis method of dual endothelin receptor antagonist aprecitentan