【结 构 式】 |
【分子编号】20482 【品名】2,3,4,5,6-pentafluorobenzenesulfonyl chloride 【CA登记号】832-53-1 |
【 分 子 式 】C6ClF5O2S 【 分 子 量 】266.575516 【元素组成】C 27.03% Cl 13.3% F 35.63% O 12% S 12.03% |
合成路线1
该中间体在本合成路线中的序号:(I)By condensation of pentafluorophenylsulfonyl chloride (I) with 3-fluoro-4-methoxyaniline (II) in pyridine.
【1】 Rosen, T.; Medina, J.C.; Flygare, J.; Shan, B.; Clark, D. (Tularik Inc.); Pentafluorobenzenesulfonamides and analogs. EP 0896533; JP 2000505459; US 5880151; WO 9730677 . |
合成路线2
该中间体在本合成路线中的序号:(I)The title sulfonamide was obtained by condensation of pentafluorophenyl sulfonyl chloride (I) with 3-hydroxy-4-methoxyaniline (II) in the presence of pyridine.
【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 . |
合成路线3
该中间体在本合成路线中的序号:(I)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 |
合成路线4
该中间体在本合成路线中的序号:(V)Formylation of 2-methoxy-5-nitroaniline (I) with formic acid (II) in Ac2O/THF yields formamide (III), whose nitro group is then hydrogenated over Pd/C in MeOH to provide aniline (IV). Treatment of (IV) with pentafluorophenylsulfonyl chloride (V) in acetone in the presence of 2,6-lutidine affords sulfonamide (VI), which is then deformylated to hydrochloride (VII) by treatment with acetyl chloride and HCl in EtOH. The target compound is finally obtained by reaction of (VII) with potassium cyanate (KCNO) in H2O/HOAc. An analogous route can be also followed for the synthesis of the target product: Treatment of 3-nitro-4-fluoroaniline (VIII) with sodium methoxide (NaOMe) in refluxing MeOH furnishes 4-methoxy-3-nitroaniline (IX), which is then condensed with pentafluorophenylsulfonyl chloride (V) in MeOH to give sulfonamide (X). Reduction of the nitro moiety of (X) by hydrogenation over Pd/C in EtOH yields aniline (XI), which is finally treated with potassium cyanate (KCNO) in H2O/HOAc.
【1】 Houze, J.; Medina, J.; Gergely, J.; et al.; T900607: Design and evaluation of a second-generation irreversible binder of beta-tubulin. Clin Cancer Res 2000, 6, Suppl., Abst 562. |
【2】 Houze, J.B. (Tularik Inc.); Arylsulfonanilide ureas. EP 1115701; US 6214880; WO 0017159 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VII), (XI) | 46684 | N-(3-amino-4-methoxyphenyl)-2,3,4,5,6-pentafluorobenzenesulfonamide | C13H9F5N2O3S | 详情 | 详情 | |
(I) | 46680 | 2-methoxy-5-nitrophenylamine; 2-methoxy-5-nitroaniline | 99-59-2 | C7H8N2O3 | 详情 | 详情 |
(II) | 14590 | Formic acid | 64-18-6 | CH2O2 | 详情 | 详情 |
(III) | 46681 | 2-methoxy-5-nitrophenylformamide | C8H8N2O4 | 详情 | 详情 | |
(IV) | 46682 | 5-amino-2-methoxyphenylformamide | C8H10N2O2 | 详情 | 详情 | |
(V) | 20482 | 2,3,4,5,6-pentafluorobenzenesulfonyl chloride | 832-53-1 | C6ClF5O2S | 详情 | 详情 |
(VI) | 46683 | 2,3,4,5,6-pentafluoro-N-[3-(formylamino)-4-methoxyphenyl]benzenesulfonamide | C14H9F5N2O4S | 详情 | 详情 | |
(VIII) | 24710 | 4-fluoro-3-nitroaniline | 364-76-1 | C6H5FN2O2 | 详情 | 详情 |
(IX) | 46685 | 4-methoxy-3-nitroaniline; 4-methoxy-3-nitrophenylamine | C7H8N2O3 | 详情 | 详情 | |
(X) | 46686 | 2,3,4,5,6-pentafluoro-N-(4-methoxy-3-nitrophenyl)benzenesulfonamide | C13H7F5N2O5S | 详情 | 详情 |