|
【结 构 式】 
|
【分子编号】20163 【品名】N-(cyclopentylmethyl)-4-methoxy-N-[(2R)oxiranylmethyl]benzenesulfonamide 【CA登记号】 |
【 分 子 式 】C16H23NO4S 【 分 子 量 】325.42896 【元素组成】C 59.05% H 7.12% N 4.3% O 19.67% S 9.85% |
合成路线1
该中间体在本合成路线中的序号：(VII)N-Cbz-L-Phenylalaninol (I) was converted to mesylate (II) on treatment with methanesulfonyl chloride and Et3N, and then treated with benzylamine (III) in the presence of NaI to give (IV). Subsequent deprotection of the Cbz group of (IV) with HBr in AcOH afforded diamine (V), which was treated with carbonyl diimidazole to produce the cyclic urea (VI). Finally, condensation with the epoxisulfonamide (VII) in the presence of NaH in DMF provided 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) | 16585 | benzyl N-[(1S)-1-benzyl-2-hydroxyethyl]carbamate | C17H19NO3 | 详情 | 详情 | |
| (II) | 20158 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-phenylpropyl methanesulfonate | C18H21NO5S | 详情 | 详情 | |
| (III) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (IV) | 20160 | benzyl (1S)-1-benzyl-2-(benzylamino)ethylcarbamate | C24H26N2O2 | 详情 | 详情 | |
| (V) | 20161 | (2S)-N(1)-benzyl-3-phenyl-1,2-propanediamine; N-[(2S)-2-amino-3-phenylpropyl]-N-benzylamine | C16H20N2 | 详情 | 详情 | |
| (VI) | 20162 | (4S)-1,4-dibenzyl-2-imidazolidinone | C17H18N2O | 详情 | 详情 | |
| (VII) | 20163 | N-(cyclopentylmethyl)-4-methoxy-N-[(2R)oxiranylmethyl]benzenesulfonamide | C16H23NO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)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 |