CP-5068
Chemical Name: (1S,5R,6S)-2-[6-(Carbamoylmethyl)-7-(methylsulfanyl)imidazo[5,1-b]thiazol-6-ium-2-yl]-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylate
项目整合开发状态: Preclinical
项目研究机构: Meiji Seika (Originator)
合成路线:Imidazothiazole (I) is converted into methylsulfanyl derivative (II) by first reaction with EtMgBr in THF followed by treatment with MeSSO2Me.Lithiation of derivative (II) by means of BuLi in THF/hexane,followed by reaction with tributyltin chloride and LiHMDS,provides tributyltin derivative (III),which is then condensed with carbapenem derivative (VI) by means of Pd(dba)3,P(2-furyl)3 and ZnCl2 in NMP to afford (VII).(Derivative (VI) in turn can be obtained by first cyclization of the diazo compound (IV) by means of ZnBr2 and Rh2Oct4 in MeOAc/THF to provide bicyclic ketoester (V),which is finally treated with triflic anhydride (Tf2O) and DIEA in acetonitrile.The target product is finally obtained by first N-alkylation of the imidazothiazole ring of (VII) with iodoacetamide (VIII) in acetonitrile followed by deprotection of the carboxylic acid by hydrogenation over Pd/C inTHF/H2O.
📌 参考资料/链接：
参考文献标题:Process for synthesizing carbapenem intermediates using a rhodium catalyst and Lewis acid
文献作者:Lynch,J.E.; Liu,T.M.-H.; Volante,R.P.(Merck & Co.,Inc.)
参考来源:US 5493018
📄 详细内容
合成路线:Imidazothiazole (I) is converted into methylsulfanyl derivative (II) by first reaction with EtMgBr in THF followed by treatment with MeSSO2Me.Lithiation of derivative (II) by means of BuLi in THF/hexane,followed by reaction with tributyltin chloride and LiHMDS,provides tributyltin derivative (III),which is then condensed with carbapenem derivative (VI) by means of Pd(dba)3,P(2-furyl)3 and ZnCl2 in NMP to afford (VII).(Derivative (VI) in turn can be obtained by first cyclization of the diazo compound (IV) by means of ZnBr2 and Rh2Oct4 in MeOAc/THF to provide bicyclic ketoester (V),which is finally treated with triflic anhydride (Tf2O) and DIEA in acetonitrile.The target product is finally obtained by first N-alkylation of the imidazothiazole ring of (VII) with iodoacetamide (VIII) in acetonitrile followed by deprotection of the carboxylic acid by hydrogenation over Pd/C inTHF/H2O.
参考文献标题:CP5068,a new carbapenem: Synthesis and structure-activity relationships
文献作者:Sakakibara,S.; Takata,T.; Yamamoto,K.; Shitara,E.; Shibasaki,Y.; Shimizu,A.; Komiya,I.
参考来源:40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000,Toronto) 2000,Abst F-1236