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【结 构 式】

【分子编号】60219

【品名】benzyl (1S)-5-[(tert-butoxycarbonyl)amino]-1-formylpentylcarbamate

【CA登记号】

【 分 子 式 】C19H28N2O5

【 分 子 量 】364.4418

【元素组成】C 62.62% H 7.74% N 7.69% O 21.95%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XII)

The esterification of N2-(benzyloxycarbonyl)-N6-(tert-butoxycarbonyl)-L-lysine (X) by means of BTU in dichloromethane/methanol gives the methyl ester (XI), which is reduced with iBu2AlH in dichloromethane to yield the corresponding aldehyde (XII). The reaction of (XII) with NaCN and Ac2O affords the acetylated cyanohydrin (XIII), which is hydrolyzed with HCl in ethyl ether/methanol to provide the alpha-hydroxyester (XIV). The trans-esterification of (XIV) with isopropanol and HCl gives the isopropyl ester (XV), which is N2 deprotected by means of H2 over Pd/C in DMF to yield the primary amine (XVI). The condensation of the lysine derivative (XVI) with the dipeptide intermediate (IX) by means of HOBT and DCC in DMF affords the tripeptide derivative (XVII), which is oxidized by means of DMP in dichloromethane to provide the alpha-oxo ester (XVIII). Finally, this compound is Boc-deprotected by means of TFA in dichloromethane to obtain the target alpha-oxo-tripeptide derivative.

1 Adang, A.E.P.; De Man, A.P.A.; Vogel, G.M.T.; Grootenhuis, P.D.J.; Smit, M.J.; Peters, C.A.M.; Visser, A.; Rewinkel, J.B.M.; van Dinther, T; Lucas, H.; Kelder, J.; van Aelst, S.; Meuleman, D.G.; van Boeckel, C.A.A.; Unique overlap in the prerequisites for thrombin inhibition and oral bioavailability resulting in potent oral antithrombotics. J Med Chem 2002, 45, 20, 4419.
2 Adang, A.E.P.; Peters, J.A.M.; Van Boeckel, C.A.A.; Rewinkel, J.B.M. (Akzo Nobel N.V.); Thrombin inhibitors. WO 9807308 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IX) 23165 (2S)-1-((2R)-2-[(tert-butoxycarbonyl)[2-(tert-butoxy)-2-oxoethyl]amino]-3-cyclohexylpropanoyl)-2-pyrrolidinecarboxylic acid C25H42N2O7 详情 详情
(X) 39273 (2S)-2-[[(benzyloxy)carbonyl]amino]-6-[(tert-butoxycarbonyl)amino]hexanoic acid C19H28N2O6 详情 详情
(XI) 60218 methyl 6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-({[(phenylmethyl)oxy]carbonyl}amino)hexanoate C20H30N2O6 详情 详情
(XII) 60219 benzyl (1S)-5-[(tert-butoxycarbonyl)amino]-1-formylpentylcarbamate C19H28N2O5 详情 详情
(XIII) 60220 1-cyano-6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-({[(phenylmethyl)oxy]carbonyl}amino)hexyl acetate C22H31N3O6 详情 详情
(XIV) 60221 methyl 7-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-hydroxy-3-({[(phenylmethyl)oxy]carbonyl}amino)heptanoate C21H32N2O7 详情 详情
(XV) 60222 1-methylethyl 7-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-hydroxy-3-({[(phenylmethyl)oxy]carbonyl}amino)heptanoate C23H36N2O7 详情 详情
(XVI) 60223 1-methylethyl 3-amino-7-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-hydroxyheptanoate C15H30N2O5 详情 详情
(XVII) 60224 1-methylethyl 3-[({1-[3-cyclohexyl-2-({[(1,1-dimethylethyl)oxy]carbonyl}{2-[(1,1-dimethylethyl)oxy]-2-oxoethyl}amino)propanoyl]-2-pyrrolidinyl}carbonyl)amino]-7-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-hydroxyheptanoate C40H70N4O11 详情 详情
(XVIII) 60225 1-methylethyl 3-[({1-[3-cyclohexyl-2-({[(1,1-dimethylethyl)oxy]carbonyl}{2-[(1,1-dimethylethyl)oxy]-2-oxoethyl}amino)propanoyl]-2-pyrrolidinyl}carbonyl)amino]-7-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-oxoheptanoate C40H68N4O11 详情 详情
Extended Information