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【结 构 式】 
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【分子编号】43931 【品名】4,8-dimethyl-1,2,4,4a,5,6-hexahydro-3H-pyrido[1,2-a]quinolin-3-one 【CA登记号】 |
【 分 子 式 】C15H19NO 【 分 子 量 】229.322 【元素组成】C 78.56% H 8.35% N 6.11% O 6.98% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Acylation of p-toluidine (I) with 3-chloropropionyl chloride afforded the beta-chloroamide (II), which was cyclized to dihydroquinolinone (III) by treatment with AlCl3 at 120 C. After protection of the N atom of (III) as the tert-butyl carbamate (IV), reduction of the 2-oxo group by NaBH4 in ethanol at -25 C, followed by acidic quench with ethanolic HCl, afforded the N-Boc-2-ethoxy derivative (V). The tandem Mannich-Michael cyclization of the alpha-ethoxycarbamate (V) with the (silyloxy)diene (VII) (derived from 1-penten-3-one (VI) in the presence of trimethylsilyl triflate) furnished the benzoquinolizinone (VIII) as a mixture of diastereoisomers. Finally, oxidation of this mixture with mercuric acetate afforded the desired delta-4 unsaturated compound.
| 【1】 Machetti, F.; Scarpi, D.; Guarna, A.; Occhiato, E.G.; Benzo[c]quinolizin-3-ones: A novel class of potent and selective nonsteroidal inhibitors of human steroid 5alpha-reductase 1. J Med Chem 2000, 43, 20, 3718. |
| 【2】 Guarna, A.; Serio, M. (Applied Research Systems ARS Holdings NV); Benzo[c]quinolizine derivs., their preparation and use as 5alpha-reductases inhibitors. EP 0880520; JP 2000504680; WO 9729107 . |
| 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) | 31228 | p-toluidine; 4-methylphenylamine | 106-49-0 | C7H9N | 详情 | 详情 |
| (II) | 43925 | 3-chloro-N-(4-methylphenyl)propanamide | C10H12ClNO | 详情 | 详情 | |
| (III) | 43926 | 6-methyl-3,4-dihydro-2(1H)-quinolinone | C10H11NO | 详情 | 详情 | |
| (IV) | 43927 | tert-butyl 6-methyl-2-oxo-3,4-dihydro-1(2H)-quinolinecarboxylate | C15H19NO3 | 详情 | 详情 | |
| (V) | 43928 | tert-butyl 2-ethoxy-6-methyl-3,4-dihydro-1(2H)-quinolinecarboxylate | C17H25NO3 | 详情 | 详情 | |
| (VI) | 43930 | 1-penten-3-one | 1629-58-9 | C5H8O | 详情 | 详情 |
| (VII) | 43929 | trimethylsilyl (Z)-1-vinyl-1-propenyl ether; trimethyl[[(Z)-1-vinyl-1-propenyl]oxy]silane | C8H16OSi | 详情 | 详情 | |
| (VIII) | 43931 | 4,8-dimethyl-1,2,4,4a,5,6-hexahydro-3H-pyrido[1,2-a]quinolin-3-one | C15H19NO | 详情 | 详情 |