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【结 构 式】 
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【分子编号】45767 【品名】(1R,2S)-1-([isobutyl[(4-nitrophenyl)sulfonyl]amino]methyl)-3-phenyl-2-([[(3S)tetrahydro-3-furanyloxy]carbonyl]amino)propyl hydrogen phosphonate 【CA登记号】 |
【 分 子 式 】C25H34N3O10PS 【 分 子 量 】599.598942 【元素组成】C 50.08% H 5.72% N 7.01% O 26.68% P 5.17% S 5.35% |
合成路线1
该中间体在本合成路线中的序号：(XVII)Esterification of the OH group of compound (XIII) with PO3H3 by means of DCC in hot pyridine gives the corresponding phosphite (XVII), which is oxidized with bis(trimethylsilyl)peroxide in bis(trimethylsilyl)azane to yield the expected phosphate (XVIII). Reduction of the nitro group of (XVIII) with H2 over Pd/C in ethyl acetate affords fosamprenavir (XIX). Finally, fosamprenavir (XIX) is treated with aqueous NaHCO3 or with calcium acetate in water to provide the corresponding salts. Alternatively, the phosphate (XIX) can be obtained directly by reaction of intermediate (XIII) with POCl3 in pyridine, followed by hydrolysis with 2N HCl.
| 【1】 Martin, L.; Castaner, R.M.; Sorbera, L.A.; Castaner, J.; Fosamprenavir. Drugs Fut 2001, 26, 3, 224. |
| 【3】 Armitage, I.G.; Singh, H.; Searle, A.D. (Glaxo Group Ltd.); Calcium (3S) tetrahydro-3-furanyl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propylcarbamate. WO 0004033 . |
| 【4】 Kaldor, I.; Hale, M.R.; Furfine, E.S.; Baker, C.T.; Tung, R.D.; Kazmierski, W.M.; Spaltenstein, A. (Vertex Pharmaceuticals Inc.); Prodrugs of aspartyl protease inhibitors. WO 9933792 . |
| 【5】 Kazmierski, W.W.; Hale, M.R.; Tung, R.D.; Furfine, E.S.; Kaldor, I.; Baker, C.T.; Spaltenstein, A. (Vertex Pharmaceuticals Inc.); Sulphonamide derivs. as prodrugs of aspartyl protease inhibitors. CA 2231700; EP 0933372; JP 1999209337; WO 9933815 . |
| 【6】 Spaltenstein, A.; Kazmierski, W.M.; Kaldor, I.; Baker, C.T.; Hale, M.R.; Tung, R.D.; Furfine, E.S. (Vertex Pharmaceuticals Inc.); Prodrugs of aspartyl protease inhibitors. WO 9933793 . |
| 【7】 Crawley, K.; Searle, A.D. (Glaxo Group Ltd.); Derivs. of (3S) tetrahydro-3-furanyl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propylcarbamate. WO 0100635 . |
| 【2】 Furfine, E.S.; Bridson, G.; Hale, M.R.; Baker, C.; Heiser, A.; Chaturvedi, P.R.; Tung, R.D.; Spaltenstein, A.; Discovery of VX-175/GW433908, a novel, water-soluble prodrug of amprenavir. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F916. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 44423 | (3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]propylcarbamate | C25H33N3O8S | 详情 | 详情 | |
| (XVII) | 45767 | (1R,2S)-1-([isobutyl[(4-nitrophenyl)sulfonyl]amino]methyl)-3-phenyl-2-([[(3S)tetrahydro-3-furanyloxy]carbonyl]amino)propyl hydrogen phosphonate | C25H34N3O10PS | 详情 | 详情 | |
| (XVIII) | 45768 | (3S)tetrahydro-3-furanyl (1S,2R)-1-benzyl-3-[isobutyl[(4-nitrophenyl)sulfonyl]amino]-2-(phosphonooxy)propylcarbamate | C25H34N3O11PS | 详情 | 详情 | |
| (XIX) | 45769 | (3S)tetrahydro-3-furanyl (1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propylcarbamate | C25H36N3O9PS | 详情 | 详情 |