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【结 构 式】 
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【分子编号】32811 【品名】N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-methoxybenzenesulfonamide 【CA登记号】 |
【 分 子 式 】C21H30N2O4S 【 分 子 量 】406.54628 【元素组成】C 62.04% H 7.44% N 6.89% O 15.74% S 7.89% |
合成路线1
该中间体在本合成路线中的序号：(X)The Grignard reaction of vinyloxirane (I) with phenylmagnesium bromide and CuCN in THF gives 4-phenyl-2-buten-1-ol (II), which is submitted to a Sharpless epoxidation with t-BuOOH and Ti(Oi-Pr)4 in dichloromethane in the presence of (-)-diethyl tartrate [(-)-DET] yielding the chiral epoxide (III). The reaction of (III) with Ti(Oi-Pr)2(N3)2 in refluxing benzene affords the 3(S)-azido-4-phenylbutane-1,2(S)-diol (IV), which is epoxidized with 2-acetoxy-2-methylpropionyl chloride (A) and NaOMe in THF to give the chiral azidoepoxide (V). The reaction of (V) with isobutylamine (VI) in hot isopropanol yields the secondary amine (VII), which is condensed with 4-methoxyphenylsulfonyl chloride (VIII) in pyridine affording the sulfonamide (IX). The reduction of the azido group of (IX) with H2 over Pd/C in methanol provides (X) with a primary amino group that is finally condensed with the succinimidinyl carbonate (XI) by means of triethylamine in acetonitrile.
| 【1】 Ghosh, A.K.; Kincaid, J.F.; Cho, W.; Walters, D.E.; Krishnan, K.; Hussain, K.A.; Koo, Y.; Cho, H.; Rudall, C.; Holland, L.; Buthod, J.; Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere. Bioorg Med Chem Lett 1998, 8, 6, 687. |
| 【2】 Hussain, K.A.; Gulnik, S.V.; Ghosh, A.K.; Erickson, J.W. (University of Illinois; US Department of Health & Human Services); Multi-drug resistant retroviral protease inhibitors and associated methods. WO 9967254 . |
| 【3】 Ghosh, A.K.; et al.; Potent HIV protease inhibitors: The development of tetrahydrofuranylglycines as novel P2-ligands and pyrazine amides as P3-ligands. J Med Chem 1993, 36, 16, 2300. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 | |
| (A) | 32808 | 2-chloro-1,1-dimethyl-2-oxoethyl acetate | 40635-66-3 | C6H9ClO3 | 详情 | 详情 |
| (I) | 32805 | 2-vinyloxirane | 930-22-3 | C4H6O | 详情 | 详情 |
| (II) | 32806 | (E)-4-phenyl-2-buten-1-ol | C10H12O | 详情 | 详情 | |
| (III) | 32807 | [(2R,3S)-3-benzyloxiranyl]methanol | 116949-62-3 | C10H12O2 | 详情 | 详情 |
| (IV) | 14544 | (2S,3S)-3-azido-4-phenyl-1,2-butanediol | C10H13N3O2 | 详情 | 详情 | |
| (V) | 14547 | (1S)-1-[(2S)oxiranyl]-2-phenylethyl azide; (2S)-2-[(1S)-1-azido-2-phenylethyl]oxirane | C10H11N3O | 详情 | 详情 | |
| (VI) | 13306 | 2-Methyl-1-propanamine; Isobutylamine | 78-81-9 | C4H11N | 详情 | 详情 |
| (VII) | 32809 | (2R,3S)-3-azido-1-(isobutylamino)-4-phenyl-2-butanol | C14H22N4O | 详情 | 详情 | |
| (VIII) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |
| (IX) | 32810 | N-[(2R,3S)-3-azido-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-methoxybenzenesulfonamide | C21H28N4O4S | 详情 | 详情 | |
| (X) | 32811 | N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-methoxybenzenesulfonamide | C21H30N2O4S | 详情 | 详情 | |
| (XI) | 32812 | 1-([[(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy)-2,5-pyrrolidinedione | C11H13NO7 | 详情 | 详情 |