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【结 构 式】 
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【分子编号】19436 【品名】N-methyl[3-(phenylsulfanyl)-1H-indol-5-yl]methanesulfonamide 【CA登记号】 |
【 分 子 式 】C16H16N2O2S2 【 分 子 量 】332.44732 【元素组成】C 57.81% H 4.85% N 8.43% O 9.63% S 19.29% |
合成路线1
该中间体在本合成路线中的序号：(V)1) The diazotation of 4-amino-N-methylbenzenemethanesulfonamide (I) with NaNO2-HCl followed by reduction with SnCl2 gives the 4-hydrazino compound (II), which is condensed with (phenylthio)acetaldehyde (III) in ethanol yielding the ethylideneamino compound (IV). The cyclization of (IV) with HCl in ethanol affords N-methyl-3-(phenylthio)-1H-indole-5-methansulfonamide (V), which is desulfurized with RaNi in refluxing ethanol-water to give N-methyl-1H-indole-5-methanesulfonamide (VI). The reaction of (VI) with oxalyl chloride and dimethylamine yields the oxalyl derivative (VII), which is finally reduced with LiAlH4 in refluxing THF.
| 【1】 Oxford, A.W. (Glaxo Group Ltd.); An indole derivative.. GB 2162522 . |
| 【2】 Coates, I.H.; Dowle, M.D. (Glaxo Group Ltd.); Heterocyclic compounds.. FR 2530625; GB 2124210; US 4816470 . |
| 【3】 Humphrey, P.P.A.; Feniuk, W.; Perren, M.J.; Oxford, A.W.; Brittain, R.T.; Prous, J.; Castaner, J.; SUMATRIPTAN SUCCINATE < Prop INNM; BAN >. Drugs Fut 1989, 14, 1, 35. |
| 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) | 19432 | (4-aminophenyl)-N-methylmethanesulfonamide; 4-amino-N-ethylbenzylmethanesulfamide | 109903-35-7 | C8H12N2O2S | 详情 | 详情 |
| (II) | 19433 | (4-hydrazinophenyl)-N-methylmethanesulfonamide | 88933-16-8 | C8H13N3O2S | 详情 | 详情 |
| (III) | 19434 | 2-(phenylsulfanyl)acetaldehyde | C8H8OS | 详情 | 详情 | |
| (IV) | 19435 | N-methyl(4-[2-[(E)-2-(phenylsulfanyl)ethylidene]hydrazino]phenyl)methanesulfonamide | C16H19N3O2S2 | 详情 | 详情 | |
| (V) | 19436 | N-methyl[3-(phenylsulfanyl)-1H-indol-5-yl]methanesulfonamide | C16H16N2O2S2 | 详情 | 详情 | |
| (VI) | 19437 | 1H-indol-5-yl-N-methylmethanesulfonamide | C10H12N2O2S | 详情 | 详情 | |
| (VII) | 19438 | N,N-dimethyl-2-(5-[[(methylamino)sulfonyl]methyl]-1H-indol-3-yl)-2-oxoacetamide | C14H17N3O4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)3) The condensation of indole (VI) with N,N-diethylchloroacetamide (X) by means of POCl3 gives 3-chloroacetyl-N-methyl-1H-indole-5-methanesulfonamide (XI), which is treated with dimethylamine (XII) in refluxing ethanol to afford the dimethylaminoacetyl derivative (XIII), which is finally reduced with NaBH4 in refluxing propanol.
| 【1】 Oxford, A.W. (Glaxo Group Ltd.); An indole derivative.. GB 2162522 . |
| 【2】 Coates, I.H.; Dowle, M.D. (Glaxo Group Ltd.); Heterocyclic compounds.. FR 2530625; GB 2124210; US 4816470 . |
| 【3】 Humphrey, P.P.A.; Feniuk, W.; Perren, M.J.; Oxford, A.W.; Brittain, R.T.; Prous, J.; Castaner, J.; SUMATRIPTAN SUCCINATE < Prop INNM; BAN >. Drugs Fut 1989, 14, 1, 35. |
| 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) | 19441 | 2-chloro-N,N-diethylacetamide | 2315-36-8 | C6H12ClNO | 详情 | 详情 |
| (I) | 19432 | (4-aminophenyl)-N-methylmethanesulfonamide; 4-amino-N-ethylbenzylmethanesulfamide | 109903-35-7 | C8H12N2O2S | 详情 | 详情 |
| (II) | 19433 | (4-hydrazinophenyl)-N-methylmethanesulfonamide | 88933-16-8 | C8H13N3O2S | 详情 | 详情 |
| (III) | 19434 | 2-(phenylsulfanyl)acetaldehyde | C8H8OS | 详情 | 详情 | |
| (IV) | 19435 | N-methyl(4-[2-[(E)-2-(phenylsulfanyl)ethylidene]hydrazino]phenyl)methanesulfonamide | C16H19N3O2S2 | 详情 | 详情 | |
| (V) | 19436 | N-methyl[3-(phenylsulfanyl)-1H-indol-5-yl]methanesulfonamide | C16H16N2O2S2 | 详情 | 详情 | |
| (VI) | 19437 | 1H-indol-5-yl-N-methylmethanesulfonamide | C10H12N2O2S | 详情 | 详情 | |
| (XI) | 19442 | [3-(2-chloroacetyl)-1H-indol-5-yl]-N-methylmethanesulfonamide | C13H15ClN2O | 详情 | 详情 | |
| (XII) | 19443 | N-methylmethanamine; N,N-dimethylamine | 124-40-3 | C2H7N | 详情 | 详情 |
| (XIII) | 19444 | [3-[2-(dimethylamino)acetyl]-1H-indol-5-yl]-N-methylmethanesulfonamide | C14H19N3O3S | 详情 | 详情 |