CRA-2059, APC-2059
[(3R,6R)-6-[4-[[4-(二氨基苯甲基苯基)苯基]甲基氨甲酰]哌拉嗪-1-羰基]氧-2,3,3a,5,6,6a-六氢呋喃[3,2-b]呋喃-3-基] 4-[[4-(二氨基基苯氨基)苯基]甲基氨甲酰]哌拉嗪-1-羧酸盐Chemical Name: (3R,3aS,6R,6aS)-3,6-Bis[4-[N-(4-guanidinobenzyl)carbamoyl]piperazin-1-ylcarbonyloxy]hexahydrofuro[3,2-b]furan
CAS No. 256649-36-2, 178972-64-0 (undefined isomer)
项目整合开发状态: Phase II
项目研究机构: Celera (Originator), Bayer (Codevelopment)
合成路线:4-Aminobenzylamine (I) was protected as the tert-butyl carbamate (II) upon treatment with Boc2O.Heating of (II) with cyanamide afforded guanidine (III).The Boc protecting group of (III) was then removed by means of trifluoroacetic acid to furnish 4-guanidinobenzylamine (IV).4-Boc-piperazine-1-carbonyl chloride (VI) (obtained by treatment of N-Boc piperazine (V) with triphosgene) was condensed with amine (IV),yielding urea (VII).The N-Boc group of (VII) was then deprotected with trifluoroacetic acid to give (VIII) (1).Dianhydromannitol (X) was converted to bischloroformate (XI) by treatment with phosgene.Then condensation of (XI) with piperazine (VIII) provided the title biscarbamate.
📌 参考资料/链接：
参考文献标题:Compsns.and methods for treating mast-cell inflammatory condition
文献作者:Gangloff,A.R.; Kuo,E.Y.-L.; Dener,J.M.; Rice,K.D.(Axys Pharmaceuticals,Inc.)
参考来源:US 6022969; WO 9609297
📄 详细内容
合成路线:4-Aminobenzylamine (I) was protected as the tert-butyl carbamate (II) upon treatment with Boc2O.Heating of (II) with cyanamide afforded guanidine (III).The Boc protecting group of (III) was then removed by means of trifluoroacetic acid to furnish 4-guanidinobenzylamine (IV).4-Boc-piperazine-1-carbonyl chloride (VI) (obtained by treatment of N-Boc piperazine (V) with triphosgene) was condensed with amine (IV),yielding urea (VII).The N-Boc group of (VII) was then deprotected with trifluoroacetic acid to give (VIII) (1).Dianhydromannitol (X) was converted to bischloroformate (XI) by treatment with phosgene.Then condensation of (XI) with piperazine (VIII) provided the title biscarbamate.
参考文献标题:Dibasic inhibitors of human mast cell tryptase.Part 2: Structure-activity relationships and requirements for potent activity
文献作者:Rice,K.D.; Wang,V.R.; Gangloff,A.R.; Kuo,E.Y.-L.; Dener,J.M.; Newcomb,W.S.; Young,W.B.; Putnam,D.; Cregar,L.; Wong,M.; Simpson,P.J.
参考来源:Bioorg Med Chem Lett 2000,10(20),2361
产品链接: CAS No. 256649-36-2››