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【结 构 式】 
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【药物名称】 【化学名称】6-Chloro-N-isopropyl-4H-thieno[2,3-e][1,2,4]thiadiazin-3-amine 1,1-dioxide 【CA登记号】220105-82-8 【 分 子 式 】C8H10ClN3O2S2 【 分 子 量 】279.7688 |
【开发单位】Novo Nordisk (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, K(ATP) Channel Activators |
合成路线1
The thiocarbamoylation of the thiophenesulfonamide (I) with isopropyl isothiocyanate in the presence of potassium tert-butoxide furnished the sulfonyl thiourea (II). This was cyclized to the thienothiadiazine derivative (III) upon treatment with phosgene and triethylamine in cold THF. The acetyl group of (III) was finally removed by hydrolysis with NaOH.
| 【1】 Tagmose, T.M.; Hansen, H.C.; Nielsen, F.E.; Mogensen, J.P.; Hansen, J.B. (Novo Nordisk A/S); Fused 1,2,4-thiadiazine derivs., their preparation and use. EP 1000066; JP 2001510195; WO 9903861 . |
| 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) | 51337 | N-[3-(aminosulfonyl)-5-chloro-2-thienyl]acetamide | C6H7ClN2O3S2 | 详情 | 详情 | |
| (II) | 51338 | N-[5-chloro-3-([[(isopropylamino)carbothioyl]amino]sulfonyl)-2-thienyl]acetamide | C10H14ClN3O3S3 | 详情 | 详情 | |
| (III) | 51339 | 4-acetyl-6-chloro-3-(isopropylamino)-2H-thieno[2,3-e][1,2,4]thiadiazine-1,1(4H)-dione | C10H12ClN3O3S2 | 详情 | 详情 |
合成路线2
In an alternative method, sulfonylation of N-isopropylguanidine (V) with 2,5-dichlorothiophene-3-sulfonyl chloride (IV) produced the sulfonyl guanidine (VI). This was then cyclized to the title compound by treatment with copper bronze and potassium carbonate in boiling DMF.
| 【1】 Nielsen, F.E.; Ebdrup, S. (Novo Nordisk A/S); Novel process. WO 0102410 . |
| 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) | 11340 | 2,5-Dichloro-3-thiophenesulfonyl chloride; 2,5-Dichlorothiophene-3-sulphonyl chloride | 56946-83-9 | C4HCl3O2S2 | 详情 | 详情 |
| (V) | 51340 | N-isopropylguanidine | C4H11N3 | 详情 | 详情 | |
| (VI) | 51341 | 2,5-dichloro-3-([[imino(isopropylamino)methyl]amino]sulfonyl)thiophene | C8H11Cl2N3O2S2 | 详情 | 详情 |