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【结 构 式】 
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【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% |
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 |