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【结 构 式】 
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【药物名称】A-293507 【化学名称】4-(4-Chlorophenoxy)-N'-hydroxythieno[2,3-c]pyridine-2-carboxamidine 【CA登记号】251994-96-4 【 分 子 式 】C14H10ClN3O2S 【 分 子 量 】319.7717 |
【开发单位】Abbott (Originator), Lilly (Originator) 【药理作用】Antiarthritic Drugs, GASTROINTESTINAL DRUGS, Inflammatory Bowel Disease, Agents for, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Anti-ICAM-1 Agents, Cell Adhesion Inhibitors, E-Selectin Inhibitors, Non-Steroidal Antiinflammatory Drugs |
合成路线1
Treatment of 3,5-dichloropyridine (I) with methyl formate (II), BuLi and diisopropyl amine (DIPA) in THF provides carboxaldehyde (III), which is converted into ester (VI) by first condensation with 4-chlorophenol (IV) by means of tBuOK in THF followed by cyclization with methyl thioglycolate (V) and Cs2CO3. Methyl ester (VI) reacts with methanolic ammonia to yield carboxamide (VII), which is then treated with trifluoroacetic anhydride (TFAA) in pyridine to furnish carbonitrile (VIII). Finally, (VIII) is converted into the desired compound by reaction with hydroxylamine hydrochloride (NH2OH·HCl) and TEA in EtOH.
| 【1】 Lartey, K.; Gunawardana, I.W.; Stout, D.M.; Bhatia, P.; Patel, M.V.; Staeger, M.A.; Boyd, S.A.; Mort, N.A.; Zhu, G.-D.; McCarty, C.M.; Stewart, A.O.; Arendsen, D.L.; Condroski, K.R.; Freeman, J.C. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory cpds.. WO 9962908 . |
| 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) | 35535 | 3,5-dichloropyridine | 2457-47-8 | C5H3Cl2N | 详情 | 详情 |
| (II) | 45474 | methyl formate | 107-31-3 | C2H4O2 | 详情 | 详情 |
| (III) | 35536 | 3,5-dichloroisonicotinaldehyde; 3,5-Dichloropyridine-4-carbaldehyde | 136590-83-5 | C6H3Cl2NO | 详情 | 详情 |
| (IV) | 35543 | 4-chlorophenol | 106-48-9 | C6H5ClO | 详情 | 详情 |
| (V) | 18838 | methyl 2-sulfanylacetate | 2365-48-2 | C3H6O2S | 详情 | 详情 |
| (VI) | 35542 | methyl 4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxylate | C15H10ClNO3S | 详情 | 详情 | |
| (VII) | 45475 | 4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxamide | C14H9ClN2O2S | 详情 | 详情 | |
| (VIII) | 45476 | 4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carbonitrile | C14H7ClN2OS | 详情 | 详情 |