新产品编号:557373
Chemical Name: 2(R)-(2-Benzothiazolylmethyl)-N-methyl-4-oxo-N-[4-(trifluoromethyl)benzyl]azetidine-1-carboxamide
CAS No. 223266-68-0
项目整合开发状态: Biological Testing
项目研究机构: Bio-Mega (Originator)
合成路线:Serine derivative (I) is converted into butyric acid derivative (II) by first treatment with isobutyl chloroformate and Et3N in THF,followed by reaction with ethereal diazomethane,Wolf rearrangement with Et3N in THF/H2O catalyzed by AgOBz and benzylation with benzyl bromide and DBU in acetonitrile.Conversion of (II) into azetidinone derivative (III) is achieved by Boc group removal by means of HCl in dioxane followed by cyclization by treatment with TMSCl,Et3N in Et2O and then t-BuMgCl.Protection of (III) using TIPSOTf and 2,5-lutidine in CH2Cl2 followed by removal of benzyl ether by hydrogenolysis over Pd(OH)2 in THF gives beta-lactam alcohol (IV),which is then oxidized by means of Dess-Martin periodinane in CH2Cl2 to yield aldehyde (V).Reaction of (V) with benzothiazole (VI) and n-BuLi in THF yields alcohol (VII),which is then deoxygenated by treatment with 1,1-(thiocarbonyl)diimidazole and DMAP in CH2Cl2 followed by reduction with Ph3SnH and AIBN in benzene to afford (VIII).Removal of the TIPS group from (VIII) by means of CsF in MeOH followed by condensation with chloride (IX) by means of KHMDS in THF finally furnishes the target product.
📌 参考资料/链接：
参考文献标题:Azetidinone derivs.for the treatment of HCMV infections
文献作者:Ogilvie,W.W.; O'Meara,J.; Deziel,R.; Yoakim,C.(Boehringer Ingelheim (Canada) Ltd.)
参考来源:EP 1021405; WO 9918072
📄 详细内容
合成路线:Serine derivative (I) is converted into butyric acid derivative (II) by first treatment with isobutyl chloroformate and Et3N in THF,followed by reaction with ethereal diazomethane,Wolf rearrangement with Et3N in THF/H2O catalyzed by AgOBz and benzylation with benzyl bromide and DBU in acetonitrile.Conversion of (II) into azetidinone derivative (III) is achieved by Boc group removal by means of HCl in dioxane followed by cyclization by treatment with TMSCl,Et3N in Et2O and then t-BuMgCl.Protection of (III) using TIPSOTf and 2,5-lutidine in CH2Cl2 followed by removal of benzyl ether by hydrogenolysis over Pd(OH)2 in THF gives beta-lactam alcohol (IV),which is then oxidized by means of Dess-Martin periodinane in CH2Cl2 to yield aldehyde (V).Reaction of (V) with benzothiazole (VI) and n-BuLi in THF yields alcohol (VII),which is then deoxygenated by treatment with 1,1-(thiocarbonyl)diimidazole and DMAP in CH2Cl2 followed by reduction with Ph3SnH and AIBN in benzene to afford (VIII).Removal of the TIPS group from (VIII) by means of CsF in MeOH followed by condensation with chloride (IX) by means of KHMDS in THF finally furnishes the target product.
参考文献标题:Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease
文献作者:Ogilvie,W.W.; Yoakim,C.; D? F.; Hach? B.; Lagac? L.; Naud,J.; O'Meara,J.A.; D閦iel,R.
参考来源:Bioorg Med Chem 1999,7(8),1521