|
【结 构 式】 
|
【药物名称】 【化学名称】2,3,5,6-Tetrahydro-1H-benzo[c]quinolizin-3-one 【CA登记号】 【 分 子 式 】C13H13NO 【 分 子 量 】199.25466 |
【开发单位】Applied Research Systems (Originator), Serono (Originator) 【药理作用】Acne Therapy, DERMATOLOGIC DRUGS, ONCOLYTIC DRUGS, Steroid 5alpha-Reductase Inhibitors |
合成路线1
Dihydroquinolinone (I) was protected as the tert-butyl carbamate (II) by condensation with di-tert-butyl dicarbonate. Reduction of (II) with NaBH4 in EtOH at -25 C, followed by reaction with ethanolic HCl provided ethoxy compound (III). Subsequent treatment of (III) with 2-silyloxy-1,3-butadiene (V) and trimethylsilyl triflate afforded benzoquinolizinone (VI), through the sequence of Mannich condensation of intermediate N-tert-Boc iminium salt (IV) with silyl enol ether (V), followed by Michael cyclization of the unsaturated ketone. Then, oxidation with mercuric acetate provided the target 4-4a unsaturated compound together with a minor amount of 1,2-unsaturated product.
| 【1】 Guarna, A.; Occhiato, E.G.; Scarpi, D.; Tsai, R.; Danza, G.; Comerci, A.; Mancina, R.; Serio, M.; Synthesis of benzo[c]quinolizin-3-ones: Selective non-steroidal inhibitors of steroid 5alpha-reductase 1. Bioorg Med Chem Lett 1998, 8, 20, 2871. |
| 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) | 18553 | 3,4-dihydro-2(1H)-quinolinone | 553-03-7 | C9H9NO | 详情 | 详情 |
| (II) | 18554 | tert-butyl 2-oxo-3,4-dihydro-1(2H)-quinolinecarboxylate | C14H17NO3 | 详情 | 详情 | |
| (III) | 18555 | tert-butyl 2-ethoxy-3,4-dihydro-1(2H)-quinolinecarboxylate | C16H23NO3 | 详情 | 详情 | |
| (IV) | 18556 | tert-butyl 3,4-dihydro-1lambda(5)-quinoline-1-carboxylate | C14H19NO2 | 详情 | 详情 | |
| (V) | 18557 | 1-methylene-2-propenyl trimethylsilyl ether; trimethyl[(1-methylene-2-propenyl)oxy]silane | 38053-91-7 | C7H14OSi | 详情 | 详情 |
| (VI) | 18558 | 1,2,4,4a,5,6-hexahydro-3H-pyrido[1,2-a]quinolin-3-one | C13H15NO | 详情 | 详情 |