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【结 构 式】 
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【药物名称】 【化学名称】Phosphoric acid 2-methoxy-5-(2,3,4,5,6-pentafluorophenylsulfonamido)phenyl mono ester 【CA登记号】253141-29-6 【 分 子 式 】C13H9F5NO7PS 【 分 子 量 】449.24898 |
【开发单位】Tularik (Originator) 【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, Antimitotic Drugs, Microtubule-Stabilizing Agents |
合成路线1
Condensation of pentafluorophenyl sulfonyl chloride (I) with 3-hydroxy-4-methoxyaniline (II) in the presence of pyridine afforded sulfonamide (III). Treatment of (III) with N,N-diisopropyl dibenzylphosphoramidite (A) and tetrazole gave phosphite ester (IV), which was subsequently oxidized to phosphate (V) by means of tert-butyl peroxide. Finally, hydrogenolysis of the benzyl phosphate ester groups of (V) in the presence of Pd/C and 1,4-cyclohexadiene furnished the title compound.
| 【1】 Flygare, J.; Medina, J.; Shan, B.; Clark, D.; Rosen, T. (Tularik Inc.); Pentafluorobenzenesulfonamides and analogs. EP 0939627; WO 9805315 . |
| 【2】 Rosen, T.; Medina, J.C.; Flygare, J.; Shan, B.; Clark, D. (Tularik Inc.); Pentafluorobenzenesulfonamides and analogs. EP 0896533; JP 2000505459; US 5880151; WO 9730677 . |
| 【3】 Houze, J.B. (Tularik Inc.); Arylsulfonanilide phosphates. WO 9967258 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 40539 | N-[bis(phenylmethoxy)phosphanyl]-N-propan-2-ylpropan-2-amine; bis(benzyloxy)phosphino-diisopropyl-amine | 108549-23-1 | C20H28NO2P | 详情 | 详情 |
| (I) | 20482 | 2,3,4,5,6-pentafluorobenzenesulfonyl chloride | 832-53-1 | C6ClF5O2S | 详情 | 详情 |
| (II) | 40539 | N-[bis(phenylmethoxy)phosphanyl]-N-propan-2-ylpropan-2-amine; bis(benzyloxy)phosphino-diisopropyl-amine | 108549-23-1 | C20H28NO2P | 详情 | 详情 |
| (III) | 40542 | 2,3,4,5,6-pentafluoro-N-(3-hydroxy-4-methoxyphenyl)benzenesulfonamide | C13H8F5NO4S | 详情 | 详情 | |
| (IV) | 40540 | dibenzyl 2-methoxy-5-[[(2,3,4,5,6-pentafluorophenyl)sulfonyl]amino]phenyl phosphite | C27H21F5NO6PS | 详情 | 详情 | |
| (V) | 40541 | dibenzyl 2-methoxy-5-[[(2,3,4,5,6-pentafluorophenyl)sulfonyl]amino]phenyl phosphate | C27H21F5NO7PS | 详情 | 详情 |