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【结 构 式】 
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【药物名称】Chlortenoxicam, Lornoxicam, HN-10000, TS-110, Ro-13-9297, CLTX, Xefocam, Taigalor, Telos, Lorcam, Acabel, Xefo, Safem 【化学名称】6-Chloro-4-hydroxy-2-methyl-N-(2-pyridyl)-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamide 1,1-dioxide 【CA登记号】70374-39-9 【 分 子 式 】C13H10ClN3O4S2 【 分 子 量 】371.82335 |
【开发单位】Nycomed Pharma (Originator), CeNeS (Licensee), Formenti (Licensee), Merckle (Licensee), Taisho (Licensee) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Antiarthritic Drugs, Osteoarthritis, Treatment of, Rheumatoid Arthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Non-Steroidal Antiinflammatory Drugs |
合成路线1
The sulfonation of 2,5-dichlorothiophene (I) with ClSO3H -SOCl2 gives 2,5-dichlorothiophene-3-sulfonic acid chloride (II), which by reaction with methylamine in CHCl3 yields the corresponding methylamide (III). The carboxylation of (III) with butyllithium and CO2 in ether affords 5-chloro-3-(N-methylsulfamoyl)thiophene-2-carboxylic acid (IV), which is esterified with PCl5 and methanol to the methyl ester (V). The condensation of (V) with methyl iodoacetate (VI) by means of NaH in DMF gives 5-chloro-3-[N-(methoxycarbonylmethyl)-N-methylsulfamoyl]thiophene-2-carboxylic acid methyl ester (VII), which is cyclized with sodium methoxide in methanol yielding 6-chloro-4-hydroxy-2-methyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxylic acid methyl ester 1,1-dioxide (VIII). Finally, this compound is treated with 2-aminopyridine (IX) in refluxing xylene.
| 【1】 Pfister, R.; Zeller, P.; Binder, D.; Hromatka, O. (F. Hoffmann-La Roche AG); Thiazine derivs. DE 2838851 . |
| 【2】 Castaner, J.; Prous, J.; Lornoxicam. Drugs Fut 1992, 17, 8, 683. |
| 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) | 11339 | 2,5-Dichlorothiophene | 3172-52-9 | C4H2Cl2S | 详情 | 详情 |
| (II) | 11340 | 2,5-Dichloro-3-thiophenesulfonyl chloride; 2,5-Dichlorothiophene-3-sulphonyl chloride | 56946-83-9 | C4HCl3O2S2 | 详情 | 详情 |
| (III) | 11341 | 2,5-Dichloro-N-methyl-3-thiophenesulfonamide | C5H5Cl2NO2S2 | 详情 | 详情 | |
| (IV) | 11342 | 5-Chloro-3-[(methylamino)sulfonyl]-2-thiophenecarboxylic acid | C6H6ClNO4S2 | 详情 | 详情 | |
| (V) | 11343 | methyl 5-chloro-3-[(methylamino)sulfonyl]-2-thiophenecarboxylate | C7H8ClNO4S2 | 详情 | 详情 | |
| (VI) | 11344 | methyl 2-iodoacetate | C3H5IO2 | 详情 | 详情 | |
| (VII) | 11345 | methyl 5-chloro-3-[[(2-methoxy-2-oxoethyl)(methyl)amino]sulfonyl]-2-thiophenecarboxylate | C10H12ClNO6S2 | 详情 | 详情 | |
| (VIII) | 11346 | methyl 6-chloro-4-hydroxy-2-methyl-1,1-dioxo-1,2-dihydro-2H-thieno[2,3-e][1,2]thiazine-3-carboxylate | C9H8ClNO5S2 | 详情 | 详情 | |
| (IX) | 11305 | 2-Pyridinamine; 2-Pyridinylamine; 2-Aminopyridine | 504-29-0 | C5H6N2 | 详情 | 详情 |