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【结 构 式】 
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【药物名称】 【化学名称】8-Chloro-6-methyl-2,3,5,6-tetrahydro-1H-benzo[c]quinolizin-3-one 【CA登记号】 【 分 子 式 】C14H14ClNO 【 分 子 量 】247.72678 |
【开发单位】Università degli Studi di Firenze (Originator) 【药理作用】Acne Therapy, DERMATOLOGIC DRUGS, ENDOCRINE DRUGS, Gynecological Disorders, Treatment of , Hirsutism Therapy, Steroid 5alpha-Reductase Type 1 Inhibitors |
合成路线1
Lactam (I) was protected as the tert-butyl carbamate (II) by treatment with Boc2O in the presence of Et3N and DMAP. After reduction of (II) with NaBH4 in EtOH at -25 C, reaction with ethanolic HCl produced the ethoxy derivative (III). Treatment with TiCl4 in CH2Cl2 at -30 C generated the intermediate iminium salt (IV), that was converted into the target benzoquinolizinone system (VI) by the tandem Mannich-Michael condensation with 2-(trimethylsilyloxy)-1,3-butadiene (V). Finally, oxidation of (V) with mercuric acetate produced the desired unsaturated compound.
| 【1】 Zorn, C.; Danza, G.; Mancina, R.; Serio, M.; Occhiato, E.G.; Scarpi, D.; Comerci, A.; Guarna, A.; Synthesis of 8-chloro-benzo[c]quinolizin-3-ones as potent and selective inhibitors of human steroid 5alpha-reductase 1. Bioorg Med Chem Lett 2000, 10, 4, 353. |
| 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) | 40942 | 6-chloro-4-methyl-3,4-dihydro-2(1H)-quinolinone | C10H10ClNO | 详情 | 详情 | |
| (II) | 40943 | tert-butyl 6-chloro-4-methyl-2-oxo-3,4-dihydro-1(2H)-quinolinecarboxylate | C15H18ClNO3 | 详情 | 详情 | |
| (III) | 40944 | tert-butyl 6-chloro-2-ethoxy-4-methyl-3,4-dihydro-1(2H)-quinolinecarboxylate | C17H24ClNO3 | 详情 | 详情 | |
| (IV) | 40945 | 1-(tert-butoxycarbonyl)-6-chloro-4-methyl-3,4-dihydroquinolinium | C15H19ClNO2 | 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) | 40946 | 8-chloro-6-methyl-1,2,4,4a,5,6-hexahydro-3H-pyrido[1,2-a]quinolin-3-one | C14H16ClNO | 详情 | 详情 |