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【结 构 式】 
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【分子编号】27811 【品名】4-iodobenzenesulfonyl chloride 【CA登记号】98-61-3 |
【 分 子 式 】C6H4ClIO2S 【 分 子 量 】302.51973 【元素组成】C 23.82% H 1.33% Cl 11.72% I 41.95% O 10.58% S 10.6% |
合成路线1
该中间体在本合成路线中的序号：(V)Palladium-catalyzed coupling of methyl 5-iodosalycilate (I) with trimethylsilyl acetylene (II) produced the ethynyl salycilate (III). The trimethylsilyl protecting group of (III) was then cleaved by treatment with KF in DMF to give (IV). On the other hand, sulfonamide (VII) was obtained by condensation of 4-iodobenzenesulfonyl chloride (V) with 2-amino-3-methylpyridine (VI). A further Suzuki coupling between acetylene (IV) and iodosulfonamide (VII) furnished diaryl acetylene (VIII). The methyl ester group of (VIII) was finally saponified with NaOH to provide the target carboxylic acid.
| 【1】 Agback, H.; Ahrgren, L.; Berglindh, T.; Haraldsson, M.; Smedegard, G.; Olsson, L.-I. (Pharmacia & Upjohn AB); Substd. salicylic acids. JP 1995501330; US 5403930; WO 9310094 . |
| 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) | 37875 | methyl 2-hydroxy-5-iodobenzoate | C8H7IO3 | 详情 | 详情 | |
| (II) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (III) | 37876 | methyl 2-hydroxy-5-[2-(trimethylsilyl)ethynyl]benzoate | C13H16O3Si | 详情 | 详情 | |
| (IV) | 37877 | methyl 5-ethynyl-2-hydroxybenzoate | C10H8O3 | 详情 | 详情 | |
| (V) | 27811 | 4-iodobenzenesulfonyl chloride | 98-61-3 | C6H4ClIO2S | 详情 | 详情 |
| (VI) | 13016 | 3-Methyl-2-pyridinylamine; 3-Methyl-2-pyridinamine; 2-Amino-3-picoline; 2-Amino-3-methylpyridine | 1603-40-3 | C6H8N2 | 详情 | 详情 |
| (VII) | 37878 | 4-iodo-N-(3-methyl-2-pyridinyl)benzenesulfonamide | C12H11IN2O2S | 详情 | 详情 | |
| (VIII) | 37879 | methyl 2-hydroxy-5-[2-(4-[[(3-methyl-2-pyridinyl)amino]sulfonyl]phenyl)ethynyl]benzoate | C22H18N2O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)The reaction of 3-hydroxypyridine (I) with (S)-glycidol 3-nitrobenzenesulfonate (II) by means of sodium hexamethyldisylazide in DMSO gives 2(S)-(3-pyridyloxymethyl)oxirane (III), which is condensed with 2-(4-nitrophenyl)ethylamine (IV) by means of triethylamine in refluxing methanol yielding the chiral isopropanol (V). The protection of the secondary amino group of (V) with tert-butoxycarbonyl anhydride affords the carbamate (VI), which is submitted to reduction at the nitro group with H2 over palladium hydroxide in ethyl acetate providing the aniline derivative (VII). The acylation of (VII) with 4-iodobenzenesulfonyl chloride (VIII) and pyridine in dichloromethane affords the sulfonamide (IX), which is finally deprotected with 6N HCl in methanol.
| 【1】 Fisher, M.H.; Mathvink, R.J.; Ok, H.O.; Parmee, E.R.; Weber, A.E. (Merck & Co., Inc.); Substd. phenyl sulfonamides as selective beta3 agonists for the treatment of diabetes and obesity. CA 2114712; EP 0611003; JP 1995010827; US 5451677; WO 9418161 . |
| 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) | 12911 | 3-Hydroxypyridine; 3-Pyridinol | 109-00-2 | C5H5NO | 详情 | 详情 |
| (II) | 16259 | (2S)oxiranylmethyl 3-nitrobenzenesulfonate; (S)-(+)-Glycidyl nosylate | 115314-14-2 | C9H9NO6S | 详情 | 详情 |
| (III) | 27807 | (2S)oxiranylmethyl 3-pyridinyl ether | C8H9NO2 | 详情 | 详情 | |
| (IV) | 26560 | 4-nitrophenethylamine | 24954-67-4 | C8H10N2O2 | 详情 | 详情 |
| (V) | 27808 | (2S)-1-[(4-nitrophenethyl)amino]-3-(3-pyridinyloxy)-2-propanol | C16H19N3O4 | 详情 | 详情 | |
| (VI) | 27809 | tert-butyl (2S)-2-hydroxy-3-(3-pyridinyloxy)propyl(4-nitrophenethyl)carbamate | C21H27N3O6 | 详情 | 详情 | |
| (VII) | 27810 | tert-butyl 4-aminophenethyl[(2S)-2-hydroxy-3-(3-pyridinyloxy)propyl]carbamate | C21H29N3O4 | 详情 | 详情 | |
| (VIII) | 27811 | 4-iodobenzenesulfonyl chloride | 98-61-3 | C6H4ClIO2S | 详情 | 详情 |
| (IX) | 27812 | tert-butyl (2S)-2-hydroxy-3-(3-pyridinyloxy)propyl(4-[[(4-iodophenyl)sulfonyl]amino]phenethyl)carbamate | C27H32IN3O6S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)The title sulfonamide was prepared by coupling 4-methoxy-3-(4-methylpiperazin-1-yl)aniline (II) with 4-iodobenzenesulfonyl chloride (I) in acetone.
| 【1】 Bromidge, S.M.; Brown, A.M.; Clarke, S.E.; Dodgson, K.; Gager, T.; Grassam, H.L.; Jeffrey, P.M.; Joiner, G.F.; King, F.D.; Middlemiss, D.N.; Moss, S.F.; Newman, H.; Riley, G.; Routledge, C.; Wyman, P.; 5-Chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046): A potent, selective, and orally bioavailable 5-HT6 receptor antagonist. J Med Chem 1999, 42, 2, 202. |
| 【2】 King, F.D.; Bromidge, S.M.; Wyman, P.A. (SmithKline Beecham plc); Sulphonamide derivs., process for their preparation, and their use as medicaments. WO 9827081 . |