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【结 构 式】 
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【分子编号】17839 【品名】6-amino-1,3-benzodioxole-5-carbonitrile 【CA登记号】 |
【 分 子 式 】C8H6N2O2 【 分 子 量 】162.14792 【元素组成】C 59.26% H 3.73% N 17.28% O 19.73% |
合成路线1
该中间体在本合成路线中的序号：(VI)5-Amino-3-methylisoxazole (I) was chlorinated with N-chlorosuccinimide (NCS) in chloroform to afford 5-amino-4-chloro-3-methylisoxazole (II) (1). Condensation of this isoxazole (II) with 3-(chlorosulfonyl)thiophene-2-carboxylic acid methyl ester (III) was effected in the presence of sodium hydride in THF to give sulfonamide (IV), which was then hydrolyzed to the acid (V) on treatment with methanolic sodium hydroxide. This acid (V) was activated by reaction with carbonyldiimidazole (CDI) in DMF, and the resulting solution of acylimidazole was then cannulated into a cooled mixture of 2-amino-4,5-(methylenedioxy)benzonitrile (VI) and sodium hydride in DMF to yield the title amide.
| 【1】 Wu, C.; et al.; Structure-activity relationships of N2-aryl-3-(isoxazolylsulfamoyl)-2-thiophenecarboxamides as selective endothelin receptor-A antagonists. J Med Chem 1997, 40, 11, 1682. |
| 【2】 Chan, M.F.; Raju, B.G.; Kois, A.; Verner, E.J.; Wu, C.; Castillo, R.S.; Yalamoori, V.; Balaji, V.N. (Texas Biotechnology Corp.); Thienyl-, furyl-, pyrrolyl- and biphenylsulfonamides and derivs. thereof that modulate the activity of endothelin. EP 0819125; JP 1999507015; WO 9631492 . |
| 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) | 17834 | 3-methyl-5-isoxazolylamine; 3-methyl-5-isoxazolamine; 5-Amino-3-methylisoxazole | 14678-02-5 | C4H6N2O | 详情 | 详情 |
| (II) | 17835 | 4-chloro-3-methyl-5-isoxazolamine; 4-chloro-3-methyl-5-isoxazolylamine | C4H5ClN2O | 详情 | 详情 | |
| (III) | 17836 | Methyl 3-(chlorosulfonyl)-2-thiophenecarboxylate; Methyl-3-chlorosulfonylthiophene-2-carboxylate | C6H5ClO4S2 | 详情 | 详情 | |
| (IV) | 17837 | methyl 3-[[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl]-2-thiophenecarboxylate | C10H9ClN2O5S2 | 详情 | 详情 | |
| (V) | 17838 | 3-[[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl]-2-thiophenecarboxylic acid | C9H7ClN2O5S2 | 详情 | 详情 | |
| (VI) | 17839 | 6-amino-1,3-benzodioxole-5-carbonitrile | C8H6N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)5-Amino-3-methylisoxazole (I) was chlorinated with N-chlorosuccinimide (NCS) in chloroform to afford 5-amino-4-chloro-3-methylisoxazole (II). Condensation of this isoxazole (II) with 3-(chlorosulfonyl)thiophene-2-carboxylic acid methyl ester (III) was effected in the presence of sodium hydride in THF to give sulfonamide (IV), which was then hydrolyzed to the acid (V) on treatment with methanolic sodium hydroxide. This acid (V) was activated by reaction with carbonyldiimidazole (CDI) in DMF, and the resulting solution of acylimidazole was then cannulated into a cooled mixture of 2-amino-4,5-(methylenedioxy)benzonitrile (VI) and sodium hydride in DMF to yield the title amide.
| 【1】 Chan, M.F.; Raju, B.G.; Kois, A.; Verner, E.J.; Wu, C.; Castillo, R.S.; Yalamoori, V.; Balaji, V.N.; Ramnarayan, K. (ImmunoPharmaceutics, Inc.); Sulfonamides and derivs. thereof that modulate the activity of endothelin. EP 0699191; EP 0870764; GB 2285625; JP 1996510744; US 5464853; WO 9427979 . |
| 【2】 Chan, M.F.; Raju, B.G.; Kois, A.; Verner, E.J.; Wu, C.; Castillo, R.S.; Yalamoori, V.; Balaji, V.N. (Texas Biotechnology Corp.); Thienyl-, furyl-, pyrrolyl- and biphenylsulfonamides and derivs. thereof that modulate the activity of endothelin. EP 0819125; JP 1999507015; WO 9631492 . |
| 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) | 17834 | 3-methyl-5-isoxazolylamine; 3-methyl-5-isoxazolamine; 5-Amino-3-methylisoxazole | 14678-02-5 | C4H6N2O | 详情 | 详情 |
| (II) | 17835 | 4-chloro-3-methyl-5-isoxazolamine; 4-chloro-3-methyl-5-isoxazolylamine | C4H5ClN2O | 详情 | 详情 | |
| (III) | 17836 | Methyl 3-(chlorosulfonyl)-2-thiophenecarboxylate; Methyl-3-chlorosulfonylthiophene-2-carboxylate | C6H5ClO4S2 | 详情 | 详情 | |
| (IV) | 17837 | methyl 3-[[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl]-2-thiophenecarboxylate | C10H9ClN2O5S2 | 详情 | 详情 | |
| (V) | 17838 | 3-[[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl]-2-thiophenecarboxylic acid | C9H7ClN2O5S2 | 详情 | 详情 | |
| (VI) | 17839 | 6-amino-1,3-benzodioxole-5-carbonitrile | C8H6N2O2 | 详情 | 详情 |