Orbofiban acetate, CS-511, SC-57099B
奥波非班 奥波非班乙酸盐Chemical Name: N-[[1-(4-Amidinophenyl)-2-oxo-3(S)-pyrrolidinyl]carbamoyl]-beta-alanine ethyl ester monoacetate
CAS No. 163250-91-7, 163250-90-6 (free base), 165800-05-5 (hydrate(4:1))
项目整合开发状态: Phase III
项目研究机构: Pfizer (Originator), Sankyo (Licensee)
合成路线:The condensation of 4-aminobenzamide (I) with N-(tert-butoxycarbonyl)-L-methionine (II) by means of 2-chloro-1-methylpyridinium iodide (CMPI) and N-methylmorpholine (NMM) in DMF gives the corresponding methioninamide (III),which is cyclized by means of trimethylsulfonium iodide and K2CO3 in hot DMSO yielding the pyrrolidinone (IV).The dehydration of (IV) with trifluoroacetic anhydride in THF affords the corresponding nitrile (V),which is deprotected with dry HCl in ethyl acetate giving the amine (VI).The condensation of (VI) with beta-alanine ethyl ester (VII) and carbonyl diimidazole (CDI) in pyridine yields the substituted urea (VIII),which is treated with hydroxylamine hydrochloride and triethylamine in ethyl acetate to afford the N-hydroxybenzamidine (IX).Finally,this compound is hydrogenated with H2 over Pd/C in acetic acid.
📌 参考资料/链接：
参考文献标题:Process for the preparation of amidino phenyl pyrrolidine betal-alanine urea analogs
文献作者:Abood,N.A.; Flynn,D.L.; Laneman,S.A.; Nosal,R.; Schretzman,L.A.(Pharmacia Corp.)
参考来源:US 5484946
📄 详细内容
合成路线:The condensation of 4-aminobenzamide (I) with N-(tert-butoxycarbonyl)-L-methionine (II) by means of 2-chloro-1-methylpyridinium iodide (CMPI) and N-methylmorpholine (NMM) in DMF gives the corresponding methioninamide (III),which is cyclized by means of trimethylsulfonium iodide and K2CO3 in hot DMSO yielding the pyrrolidinone (IV).The dehydration of (IV) with trifluoroacetic anhydride in THF affords the corresponding nitrile (V),which is deprotected with dry HCl in ethyl acetate giving the amine (VI).The condensation of (VI) with beta-alanine ethyl ester (VII) and carbonyl diimidazole (CDI) in pyridine yields the substituted urea (VIII),which is treated with hydroxylamine hydrochloride and triethylamine in ethyl acetate to afford the N-hydroxybenzamidine (IX).Finally,this compound is hydrogenated with H2 over Pd/C in acetic acid.
参考文献标题:Orbofiban Acetate
文献作者:Castar,J.; Merlos,M.; Leeson,P.A.
参考来源:Drugs Fut 1998,23(11),1190-1198