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【结 构 式】 
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【药物名称】VB-19026 【化学名称】N-[3-[3(S)-Benzyl-5-oxo-1,4-diazaspiro[5.5]undec-4-yl]-2(S)-hydroxypropyl]-N-(cyclopentylmethyl)-4-methoxybenzenesulfonamide 【CA登记号】 【 分 子 式 】C32H45N3O5S 【 分 子 量 】583.79655 |
【开发单位】Vertex (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, HIV Protease Inhibitors |
合成路线1
Reductive alkylation of aminoester (I) with N-Cbz-L-phenylalaninal (II) using NaBH3CN and AcOH in DMF provided compound (III). Subsequent deprotection of the Cbz group of (III) with HBr in AcOH afforded the diamine salt (IV), which upon basification with diisopropylamine resulted in lactamization to produce piperazinone (V). The secondary amine of (V) was then protected by alkylation with benzyl bromide to give (VI), which was condensed with the epoxisulfonamide (VII) in the presence of NaH in DMF to furnish (VIII). Finally, hydrogenolysis of the N-benzyl group in the presence of Pd(OH)2 yielded the target compound.
| 【1】 Salituro, F.G.; Baker, C.T.; Court, J.J.; Deininger, D.D.; Kim, E.E.; Li, B.; Novak, P.M.; Rao, B.G.; Pazhanisamy, S.; Porter, M.D.; Schairer, W.C.; Tung, R.D.; Design and synthesis of novel conformationally restricted HIV protease inhibitors. Bioorg Med Chem Lett 1998, 8, 24, 3637. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 20164 | methyl 1-aminocyclohexanecarboxylate | C8H15NO2 | 详情 | 详情 | |
| (II) | 16586 | benzyl N-[(1S)-1-benzyl-2-oxoethyl]carbamate | C17H17NO3 | 详情 | 详情 | |
| (III) | 20166 | methyl 1-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-phenylpropyl)amino]cyclohexanecarboxylate | C25H32N2O4 | 详情 | 详情 | |
| (IV) | 20167 | methyl 1-[[(2S)-2-amino-3-phenylpropyl]amino]cyclohexanecarboxylate hydrobromide | C17H27BrN2O2 | 详情 | 详情 | |
| (V) | 20168 | (3S)-3-benzyl-1,4-diazaspiro[5.5]undecan-5-one | C16H22N2O | 详情 | 详情 | |
| (VI) | 20169 | (3S)-1,3-dibenzyl-1,4-diazaspiro[5.5]undecan-5-one | C23H28N2O | 详情 | 详情 | |
| (VII) | 20163 | N-(cyclopentylmethyl)-4-methoxy-N-[(2R)oxiranylmethyl]benzenesulfonamide | C16H23NO4S | 详情 | 详情 | |
| (VIII) | 20171 | N-(cyclopentylmethyl)-N-[(2S)-3-[(3S)-1,3-dibenzyl-5-oxo-1,4-diazaspiro[5.5]undec-4-yl]-2-hydroxypropyl]-4-methoxybenzenesulfonamide | C39H51N3O5S | 详情 | 详情 |