BMS-214662
1-((1H-咪唑-4-基)甲基)-3-苄基-4-(噻吩-2-基磺酰基)-2,3,4,5-四氢-1H-苯并[e][1,4]二氮杂卓-7-甲腈 (R)-1-((1H-咪唑-4-基)甲基)-3-苄基-4-(噻吩-2-基磺酰基)-2,3,4,5-四氢-1H-苯并[E][1,4]二氮杂-7-甲腈盐酸盐 Chemical Name: 3(R)-Benzyl-1-(1H-imidazol-5-ylmethyl)-4-(2-thienylsulfonyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carbonitrile
CAS No. 195987-41-8, 195981-08-9 (monoHCl)
项目整合开发状态: Phase II
项目研究机构: Bristol-Myers Squibb (Originator), National Cancer Institute (Codevelopment)
合成路线:The cyclization between 5-bromoisatoic anhydride (I) and D-phenylalanine methyl ester (II) in the presence of DMAP in refluxing pyridine produced the benzodiazepindione (III),which was further reduced to the benzodiazepine (IV) by treatment with borane in THF.Displacement of the bromide group of (IV) with cuprous cyanide in hot N-methylpyrrolidone furnished nitrile (V).Acylation of the aliphatic nitrogen of (V) with 2-thienylsulfonyl chloride (VI) gave rise to sulfonamide (VII).Finally,the title compound was obtained by reductive alkylation of (VII) with 4-formylimidazole (VIII) by means of either treatment with sodium triacetoxyborohydride or,in an improved procedure,using triethylsilane in the presence of trifluoroacetic acid.
📌 参考资料/链接：
参考文献标题:Inhibitors of farnesyl protein transferase
文献作者:Ding,C.Z.; Hunt,J.T.; Kim,S.-H.; Mitt,T.; Bhide,R.; Leftheris,K.(Bristol-Myers Squibb Co.)
参考来源:EP 0892797; JP 2000502356; US 6011029; WO 9730992
📄 详细内容
合成路线:The cyclization between 5-bromoisatoic anhydride (I) and D-phenylalanine methyl ester (II) in the presence of DMAP in refluxing pyridine produced the benzodiazepindione (III),which was further reduced to the benzodiazepine (IV) by treatment with borane in THF.Displacement of the bromide group of (IV) with cuprous cyanide in hot N-methylpyrrolidone furnished nitrile (V).Acylation of the aliphatic nitrogen of (V) with 2-thienylsulfonyl chloride (VI) gave rise to sulfonamide (VII).Finally,the title compound was obtained by reductive alkylation of (VII) with 4-formylimidazole (VIII) by means of either treatment with sodium triacetoxyborohydride or,in an improved procedure,using triethylsilane in the presence of trifluoroacetic acid.
参考文献标题:Discovery of (R)-7-cyano-2,3,4,5-tetrahydro-1-(1-H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662),a farnesyltransferase inhibitor with potent preclinical antitumor activity
文献作者:Batorsky,R.; Hunt,J.T.; Ding,C.Z.; et al.
参考来源:J Med Chem 2000,43(20),3557
合成路线:The cyclization between 5-bromoisatoic anhydride (I) and D-phenylalanine methyl ester (II) in the presence of DMAP in refluxing pyridine produced the benzodiazepindione (III),which was further reduced to the benzodiazepine (IV) by treatment with borane in THF.Displacement of the bromide group of (IV) with cuprous cyanide in hot N-methylpyrrolidone furnished nitrile (V).Acylation of the aliphatic nitrogen of (V) with 2-thienylsulfonyl chloride (VI) gave rise to sulfonamide (VII).Finally,the title compound was obtained by reductive alkylation of (VII) with 4-formylimidazole (VIII) by means of either treatment with sodium triacetoxyborohydride or,in an improved procedure,using triethylsilane in the presence of trifluoroacetic acid.
参考文献标题:Novel triethylsilane mediated reductive N-alkylation of amines: Improved synthesis of 1-(4-imidazolyl)methyl-4-sulfonylbenzodiazepines new farnesyltransferase inhibitors
文献作者:Chen,B.C.; et al.
参考来源:Tetrahedron Lett 2001,42(7),1245
产品链接: CAS No. 195987-41-8›› 产品链接: CAS No.195981-08-9››