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【结 构 式】 
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【药物名称】L-870810 【化学名称】5-(1,1-Dioxoperhydro-1,2-thiazin-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide 【CA登记号】410544-95-5, 410545-86-7 (Na salt) 【 分 子 式 】C20H19FN4O4S 【 分 子 量 】430.46123 |
【开发单位】Merck & Co. (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, HIV Integrase Inhibitors |
合成路线1
Mitsunobu coupling between isopropyl 3-(hydroxymethyl)pyridine-2-carboxylate (I) and N-tosyl glycine methyl ester (II) affords amino diester (III). Diester (III) is subsequently converted to the naphthyridine (IV) under Dieckmann cyclization conditions. Bromination of naphthyridine (IV) by means of N-bromosuccinimide provides (V). The methyl ester group of (V) is then displaced with 4-fluorobenzylamine (VI) to furnish amide (VII). Finally, copper-catalyzed displacement of the bromide (VII) with butanesultam (VIII) provides the title compound.
| 【1】 Young, S.D.; Guare, J.P.; Wai, J.S.; Fisher, T.E.; Perlow, D.S.; Anthony, N.J.; Egbertson, M.; Gomez, R.P.; Kuo, M.S.; Tran, L.; Zhuang, L.; Langford, H.M.; Melamed, J.Y.; Bennett, J.J.; Embrey, M.; Jolly, S.M.; Funk, T.W. (Merck & Co., Inc.); Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors. WO 0230930; WO 0230931 . |
| 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) | 57743 | isopropyl 3-(hydroxymethyl)-2-pyridinecarboxylate | C10H13NO3 | 详情 | 详情 | |
| (II) | 57744 | methyl 2-{[(4-methylphenyl)sulfonyl]amino}acetate | 2645-02-5 | C10H13NO4S | 详情 | 详情 |
| (III) | 57745 | isopropyl 3-({(2-methoxy-2-oxoethyl)[(4-methylphenyl)sulfonyl]amino}methyl)-2-pyridinecarboxylate | C20H24N2O6S | 详情 | 详情 | |
| (IV) | 57746 | methyl 8-hydroxy[1,6]naphthyridine-7-carboxylate | C10H8N2O3 | 详情 | 详情 | |
| (V) | 57747 | methyl 5-bromo-8-hydroxy[1,6]naphthyridine-7-carboxylate | C10H7BrN2O3 | 详情 | 详情 | |
| (VI) | 31095 | 4-fluorobenzylamine; (4-fluorophenyl)methanamine | 140-75-0 | C7H8FN | 详情 | 详情 |
| (VII) | 57748 | 5-bromo-N-(4-fluorobenzyl)-8-hydroxy[1,6]naphthyridine-7-carboxamide | C16H11BrFN3O2 | 详情 | 详情 | |
| (VIII) | 57749 | 1lambda~6~,2-thiazinane-1,1-dione | C4H9NO2S | 详情 | 详情 |