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【结 构 式】 
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【分子编号】56052 【品名】3,6-dichloro-1lambda~6~-thieno[3,2-e][1,2,4]thiadiazine-1,1(4H)-dione 【CA登记号】 |
【 分 子 式 】C5H2Cl2N2O2S2 【 分 子 量 】257.12056 【元素组成】C 23.36% H 0.78% Cl 27.58% N 10.9% O 12.45% S 24.94% |
合成路线1
该中间体在本合成路线中的序号：(VI)The title compound can be obtained by several synthetic procedures. Esterification of the thiophenecarboxylic acid (I) with simultaneous N-t-butyl group cleavage in ethanolic HCl affords (II). Ethyl ester (II) is then converted to hydrazide (III) with hydrazine hydrate. Reaction of (III) with NaNO2/HCl leads to the acyl azide (IV), which is subsequently subjected to Curtius rearrangement in boiling toluene to produce the thienothiadiazine derivative (V). Condensation of (V) with isopropylamine (VII) by heating with P2O5 furnishes the target compound in low yield. In an improved method, chlorination of (V) in the presence of POCl3 leads to (VI), which is further reacted with isopropylamine (VII) to afford the title compound
| 【1】 Nielsen, F.E.; Bodvarsdottir, T.B.; Worsaae, A.; et al.; 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells. J. Med. Chem. 2002, 45, 19, 4171. |
| 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) | 61482 | 2-[(tert-butylamino)sulfonyl]-5-chloro-3-thiophenecarboxylic acid | C9H12ClNO4S2 | 详情 | 详情 | |
| (II) | 61483 | ethyl 2-(aminosulfonyl)-5-chloro-3-thiophenecarboxylate | C7H8ClNO4S2 | 详情 | 详情 | |
| (III) | 61484 | 5-chloro-3-(hydrazinocarbonyl)-2-thiophenesulfonamide | C5H6ClN3O3S2 | 详情 | 详情 | |
| (IV) | 61485 | 2-(aminosulfonyl)-5-chloro-3-thiophenecarbonyl azide | C5H3ClN4O3S2 | 详情 | 详情 | |
| (V) | 61486 | 6-chloro-1lambda~6~-thieno[3,2-e][1,2,4]thiadiazine-1,1,3(2H,4H)-trione | C5H3ClN2O3S2 | 详情 | 详情 | |
| (VI) | 56052 | 3,6-dichloro-1lambda~6~-thieno[3,2-e][1,2,4]thiadiazine-1,1(4H)-dione | C5H2Cl2N2O2S2 | 详情 | 详情 | |
| (VII) | 23933 | 2-Propanamine; Isopropylamine | 75-31-0 | C3H9N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The known dichloro thienothiadiazine (I) was condensed with 1-methylcyclopropylamine (II) to produce the target 3-amino thienothiadiazine.
| 【1】 Hansen, J.B.; Nielsen, F.E. (Novo Nordisk A/S); Fused 1,2,4-thiadiazine derivs., their preparation and use. EP 1140945; US 6329367; WO 0037474 . |