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【结 构 式】 
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【药物名称】A-249377 【化学名称】4-(4-Bromophenoxy)thieno[2,3-c]pyridine-2-carboxamide 【CA登记号】 【 分 子 式 】C14H9BrN2O2S 【 分 子 量 】349.20803 |
【开发单位】Abbott (Originator), Icos (Codevelopment) 【药理作用】Antiallergy/Antiasthmatic Drugs, Antiarthritic Drugs, Asthma Therapy, RESPIRATORY DRUGS, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Anti-ICAM-1 Agents, Cell Adhesion Inhibitors, E-Selectin Inhibitors |
合成路线1
The formylation of 3,5-dichloropyridine (I) with methyl formate (II), BuLi and DIEA in THF gives 3,5-dichloropyridine-4-carbaldehyde (III), which is treated with 4-bromophenol (IV) and potassium tert-butoxide in hot THF to yield the adduct (V). This compound, without isolation is cyclized with methyl 2-mercaptoacetate (VI) by means of Cs2CO3 to afford 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylic acid methyl ester (VII), which is finally treated with hot methanolic ammonia in a sealed tube to give the target amide.
| 【1】 Zhu, G.-D.; et al.; Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)theino[2,3-c]pyridines with fine-tuning at C-2 carbamides. J Med Chem 2001, 44, 21, 3469. |
| 【2】 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) | 25313 | 4-bromophenol | 106-41-2 | C6H5BrO | 详情 | 详情 |
| (V) | 52015 | 3-(4-bromophenoxy)-5-chloroisonicotinaldehyde | C12H7BrClNO2 | 详情 | 详情 | |
| (VI) | 18838 | methyl 2-sulfanylacetate | 2365-48-2 | C3H6O2S | 详情 | 详情 |
| (VII) | 52016 | methyl 4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxylate | C15H10BrNO3S | 详情 | 详情 |