新产品编号:296343
Chemical Name: 3-[2-Oxo-3-[1-(2-thienylsulfonyl)piperidin-4-yl]perhydro-1,3-diazepin-1-yl]benzamidine hydrochloride
CAS No. 198824-33-8 (free base)
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The condensation of 3-cyanophenyl isocyanate (I) with N-Boc-4-aminopiperidine (II) produced the corresponding urea (III).The diazepinone system (V) was then obtained by dialkylation of the urea (III) functionality with 1,4-dibromobutane (IV) in the presence of NaH.After acid cleavage of the Boc protecting group of (V),the resulting piperidine (VI) was acylated with 2-thiophenesulfonyl chloride (VII) to give sulfonamide (VIII).Addition of methanol to the cyano group of (VIII) in the presence of anhydrous HCl in MeOAc furnished imidate (IX).This was then converted to the corresponding amidine by treatment with either methanolic ammonia or (NH4)2CO3,followed by conversion to the title hydrochloride salt.
📌 参考资料/链接：
参考文献标题:N-(Amidinophenyl)-N'-(substd.)-3H-2,4-benzodiazepin-3-one derivs.as factor Xa inhibitors
文献作者:Maduskuie,T.P.Jr.; Galemmo,R.A.Jr.; Dominguez,C.; Quan,M.L.; Rossi,K.A.; Stouten,P.F.W.; Sun,J.H.; Wells,B.L.(DuPont Pharmaceuticals Co.)
参考来源:EP 0960104; US 5925635; WO 9738984
📄 详细内容
合成路线:The condensation of 3-cyanophenyl isocyanate (I) with N-Boc-4-aminopiperidine (II) produced the corresponding urea (III).The diazepinone system (V) was then obtained by dialkylation of the urea (III) functionality with 1,4-dibromobutane (IV) in the presence of NaH.After acid cleavage of the Boc protecting group of (V),the resulting piperidine (VI) was acylated with 2-thiophenesulfonyl chloride (VII) to give sulfonamide (VIII).Addition of methanol to the cyano group of (VIII) in the presence of anhydrous HCl in MeOAc furnished imidate (IX).This was then converted to the corresponding amidine by treatment with either methanolic ammonia or (NH4)2CO3,followed by conversion to the title hydrochloride salt.
参考文献标题:The de novo design and synthesis of cyclic urea inhibitors of factor Xa: Optimization of the S4 ligand
文献作者:Galemmo,R.A.Jr.; Wells,B.L.; Rossi,K.A.; Alexander,R.S.; Dominguez,C.; Maduskuie,T.P.; Stouten,P.F.; Wright,M.R.; Aungst,B.J.; Wong,P.C.; Knabb,R.M.; Wexler,R.R.
参考来源:Bioorg Med Chem Lett 2000,10(3),301