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【结 构 式】 
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【分子编号】18660 【品名】5-chloro-1H-1,2-benzisothiazole-1,1,3(2H)-trione 【CA登记号】 |
【 分 子 式 】C7H4ClNO3S 【 分 子 量 】217.6324 【元素组成】C 38.63% H 1.85% Cl 16.29% N 6.44% O 22.05% S 14.73% |
合成路线1
该中间体在本合成路线中的序号：(III)Ortho lithiation of sulfonamide (I) with n-butyllithium, followed by carbonation with CO2 afforded benzoic acid (II). Subsequent cyclization with PPA with concomitant elimination of the N-tert-butyl group provided the saccharin analogue (III). Alkylation of the sodium salt of (III) with 1,4-dibromobutane (IV) in DMF yielded bromide (V). The reductive alkylation of 2-aminophenol (VI) with 1-tert-butoxycarbonyl-4-piperidone (VII) in the presence of sodium tri(acetoxy)borohydride provided the aminopiperidine (VIII), which was cyclized with triphosgene to afford benzoxazolone (IX). Then, removal of the N-Boc protecting group provided piperidine (X), which was finally alkylated with bromide (V) in the presence of Et3N in DMF at 80 C to furnish the title compound.
| 【1】 Nerenberg, J.B.; Erb, J.M.; Thompson, W.J.; Lee, H.Y.; Guare, J.P.; Munson, P.M.; Bergman, J.M.; Huff, J.R.; Broten, T.P.; Chang, R.S.; Chen, T.B..; O'Malley, S.; Schorn, T.W.; Scott, A.L.; Design and synthesis of N-alkylated saccharins as selective alpha1-a adrenergic receptor antagonists. Bioorg Med Chem Lett 1998, 8, 18, 2467. |
| 【2】 Lombardino, J.G.; Preparation of substituted 1,2-benzoisothiazolin-3-one 3 1,1-dioxides (o-benzoic sulfimides). J Org Chem 1971, 36, 13, 1843. |
| 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) | 18658 | N-(tert-butyl)-4-chlorobenzenesulfonamide | C10H14ClNO2S | 详情 | 详情 | |
| (II) | 18659 | 2-[(tert-butylamino)sulfonyl]-5-chlorobenzoic acid | C11H14ClNO4S | 详情 | 详情 | |
| (III) | 18660 | 5-chloro-1H-1,2-benzisothiazole-1,1,3(2H)-trione | C7H4ClNO3S | 详情 | 详情 | |
| (IV) | 11883 | 1,4-Dibromobutane; 1,4-Butylene bromide | 110-52-1 | C4H8Br2 | 详情 | 详情 |
| (V) | 18400 | 2-(4-bromobutyl)-5-chloro-1H-1,2-benzisothiazole-1,1,3(2H)-trione | C11H11BrClNO3S | 详情 | 详情 | |
| (VI) | 18663 | o-aminophenol; 2-aminophenol | 95-55-6 | C6H7NO | 详情 | 详情 |
| (VII) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (VIII) | 18665 | tert-butyl 4-(2-hydroxyanilino)-1-piperidinecarboxylate | C16H24N2O3 | 详情 | 详情 | |
| (IX) | 18666 | tert-butyl 4-[2-oxo-1,3-benzoxazol-3(2H)-yl]-1-piperidinecarboxylate | C17H22N2O4 | 详情 | 详情 | |
| (X) | 18667 | 3-(4-piperidinyl)-1,3-benzoxazol-2(3H)-one | C12H14N2O2 | 详情 | 详情 |