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【结 构 式】 
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【分子编号】54658 【品名】2,2-dimethyl-N-phenyl-2H-chromene-6-sulfonamide 【CA登记号】 |
【 分 子 式 】C17H17NO3S 【 分 子 量 】315.39292 【元素组成】C 64.74% H 5.43% N 4.44% O 15.22% S 10.17% |
合成路线1
该中间体在本合成路线中的序号：(IV)Lithiation of 6-bromo-2,2-dimethyl-2H-1-benzopyran (I), followed by treatment with sulfur dioxide, gave the sulfinic acid (II), which was subsequently chlorinated to sulfonyl chloride (III) employing SO2Cl2. Condensation of sulfonyl chloride (III) with aniline furnished the target N-phenyl sulfonamide (IV).
| 【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); Benzopyrans and pharmaceutical compsns. containing them. EP 0828733; JP 1999505820; US 5905156; WO 9637490 . |
| 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) | 34890 | 6-bromo-2,2-dimethyl-2H-chromene | C11H11BrO | 详情 | 详情 | |
| (II) | 54657 | 2,2-dimethyl-2H-chromene-6-sulfinic acid | C11H12O3S | 详情 | 详情 | |
| (III) | 34892 | 2,2-dimethyl-2H-chromene-6-sulfonyl chloride | C11H11ClO3S | 详情 | 详情 | |
| (IV) | 54658 | 2,2-dimethyl-N-phenyl-2H-chromene-6-sulfonamide | C17H17NO3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)In a different method, sodium 4-hydroxybenzenesulfonate (V) was converted to the sulfonyl chloride (VI) upon treatment with thionyl chloride in hot 1,2-dichloroethane. Reaction of acid chloride (VI) with aniline provided sulfonamide (VII). Alkylation of the phenolic hydroxyl group of (VII) with 3-chloro-3-methyl-1-butyne (VIII) in the presence of DBU and CuCl gave the propargyl ether (IX), which was then cyclized to benzopyran (IV) under Claisen rearrangement conditions.
| 【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); Benzopyrans and pharmaceutical compsns. containing them. EP 0828733; JP 1999505820; US 5905156; WO 9637490 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 54658 | 2,2-dimethyl-N-phenyl-2H-chromene-6-sulfonamide | C17H17NO3S | 详情 | 详情 | |
| (V) | 54659 | sodium 4-hydroxybenzenesulfonate | C6H5NaO4S | 详情 | 详情 | |
| (VI) | 54660 | 4-hydroxybenzenesulfonyl chloride | C6H5ClO3S | 详情 | 详情 | |
| (VII) | 54661 | 4-hydroxy-N-phenylbenzenesulfonamide | C12H11NO3S | 详情 | 详情 | |
| (VIII) | 22416 | 3-chloro-3-methyl-1-butyne | 1111-97-3 | C5H7Cl | 详情 | 详情 |
| (IX) | 54662 | 4-[(1,1-dimethyl-2-propynyl)oxy]-N-phenylbenzenesulfonamide | C17H17NO3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)Asymmetric epoxidation of benzopyran (IV) using NaOCl in the presence of the chiral catalyst (S,S)-(+)-N,N'-bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminomanganese (III) chloride produced the desired (S,S)-epoxide (X). The title compound was then obtained by oxirane ring opening in (X) with the lithium derivative of 2-piperidinone (XI) in hot THF.
| 【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); Benzopyrans and pharmaceutical compsns. containing them. EP 0828733; JP 1999505820; US 5905156; WO 9637490 . |