|
【结 构 式】 
|
【药物名称】 【化学名称】3-[2-Amino-3-(pivaloyl)imidazo[1,2-a]pyridin-6-yl]-N-methyl-3-phenyl-2(E)-propenamide 【CA登记号】 【 分 子 式 】C22H24N4O2 【 分 子 量 】376.46218 |
【开发单位】Lilly (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Anti-Rhinovirus Drugs, Antiviral Drugs |
合成路线1
Ketone (III) was prepared by Friedel-Crafts acylation of benzene (II) with 6-chloronicotinyl chloride (I). Horner-Emmons reaction of (III) with diethyl (N-methylcarbamoylmethyl)phosphonate (IV) using potassium hexamethyl-disilazide produced a 3:1 mixture of E (V) and Z olefins (VI). The desired E isomer (V) was isolated by column chromatography and then treated with bromoketone (VII) to afford the betaine (VIII). Finally, the target imidazopyridine was obtained by condensation of (VIII) with cyanamide in the presence of K2CO3.
| 【1】 Alvarez-Builla, J.; Ezquerra, J.; Vega, J.A.; Vaquero, J.J.; Hamdouchi, C.; Heinz, B.A.; Short synthesis and anti-rhinoviral activity of imidazo[1,2-a]pyridines: The effect of acyl groups at 3-position. Bioorg Med Chem Lett 1999, 9, 10, 1391. |
| 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) | 30256 | 6-chloronicotinoyl chloride | 58757-38-3 | C6H3Cl2NO | 详情 | 详情 |
| (II) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (III) | 30257 | (6-chloro-3-pyridinyl)(phenyl)methanone | C12H8ClNO | 详情 | 详情 | |
| (IV) | 30262 | diethyl 2-(methylamino)-2-oxoethylphosphonate | C7H16NO4P | 详情 | 详情 | |
| (V) | 30807 | (E)-3-(6-chloro-3-pyridinyl)-N-methyl-3-phenyl-2-propenamide | C15H13ClN2O | 详情 | 详情 | |
| (VI) | 30808 | (Z)-3-(6-chloro-3-pyridinyl)-N-methyl-3-phenyl-2-propenamide | C15H13ClN2O | 详情 | 详情 | |
| (VII) | 30809 | 1-bromo-3,3-dimethyl-2-butanone | 5469-26-1 | C6H11BrO | 详情 | 详情 |
| (VIII) | 30810 | 1-[2-Chloro-5-[2-(N-metylcarbamoyl)-1-phenylvinyl]pyridinium-1-yl]-3,3-dimethyl-2-oxo-1-butanide | C21H23ClN2O2 | 详情 | 详情 |