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【结 构 式】 
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【药物名称】Nanterinone, UK-61260-27(mesylate), UK-61260 【化学名称】6-(2,4-Dimethylimidazol-1-yl)-8-methylquinolin-2(1H)-one 【CA登记号】102791-47-9, 102791-74-2 (mesylate salt) 【 分 子 式 】C15H15N3O 【 分 子 量 】253.3063 |
【开发单位】Pfizer (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Vasodilators, Phosphodiesterase III Inhibitors |
合成路线1
The condensation of 4-fluoro-2-methylnitrobenzene (I) with 2,4-dimethyl-1H-imidazole (II) by means of Na2CO3 in hot DMF gives 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylnitrobenzene (III), which is reduced with SnCl2 in refluxing ethanol yielding the corresponding aniline (IV).The condensation of (IV) with trans-3-ethoxypropenoyl chloride in anhydrous pyridine affords the anilide (VI), which is finally cyclized by means of 98% H2SO4.
| 【1】 Roberts, D.A.; Campbell, S.F. (Pfizer Inc.); Quinolone inotropic agents. AU 8543032; EP 0166533; ES 8608874; ES 8801797; JP 1986000082; US 4728653 . |
| 【2】 Alabaster, C.T.; Bell, A.S.; Campbell, S.F.; Ellis, P.; Henderson, C.G.; Morris, D.S.; Roberts, D.A.; Ruddock, K.S.; Samuels, G.M.R.; Stefaniak, M.H.; 2(1H)-Quinolinones with cardiac stimulant activity. 2. Synthesis and biological activities of 6-(N-linked, five-membered heteroaryl) derivatives. J Med Chem 1989, 32, 3, 575-83. |
| 【3】 Prous, J.; Castaner, J.; NANTERINONE < Prop INN>. Drugs Fut 1989, 14, 4, 328. |
| 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) | 20612 | 4-Fluoro-2-methyl-1-nitrobenzene; 2-Nitro-5-fluorotoluene | 446-33-3 | C7H6FNO2 | 详情 | 详情 |
| (II) | 20613 | 2,4-dimethyl-1H-imidazole | 930-62-1 | C5H8N2 | 详情 | 详情 |
| (III) | 20614 | 2,4-dimethyl-1-(3-methyl-4-nitrophenyl)-1H-imidazole | C12H13N3O2 | 详情 | 详情 | |
| (IV) | 20615 | 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylaniline; 4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylphenylamine | C12H15N3 | 详情 | 详情 | |
| (V) | 20616 | (E)-3-ethoxy-2-propenoyl chloride | 99471-66-6 | C5H7ClO2 | 详情 | 详情 |
| (VI) | 20617 | (E)-N-[4-(2,4-dimethyl-1H-imidazol-1-yl)-2-methylphenyl]-3-ethoxy-2-propenamide | C17H21N3O2 | 详情 | 详情 |