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【结 构 式】 
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【药物名称】LG-120830 【化学名称】3-Fluoro-5-(2,2,4-trimethyl-1,2-dihydro-6-quinolinyl)benzonitrile 【CA登记号】179896-03-8 【 分 子 式 】C19H17FN2 【 分 子 量 】292.35914 |
【开发单位】Ligand (Originator) 【药理作用】Oncolytic Drugs, Progesterone Receptor Antagonists |
合成路线1
The Skraup reaction of 4-bromoaniline (I) with acetone and iodine afforded dihydroquinoline (II), which was protected as the tert-butyl carbamate (III) with Boc2O in the presence of n-BuLi. Subsequent lithium-halogen exchange in (III), followed by treatment with trimethyl borate provided boronic acid (IV). Nitrile (VI) was obtained by treatment of 1,3-dibromo-5-fluorobenzene (V) with cuprous cyanide in DMF. Then, Suzuki coupling of boronic acid (IV) with bromobenzonitrile (VI) using tetrakis(triphenylphosphine)-palladium produced the 6-arylquinoline (VII). The Boc group of (VII) was finally removed with trifluoroacetic acid to furnish the title compound.
| 【1】 Pooley, C.L.F.; Edwards, J.P.; Goldman, M.E.; Wang, M.-W.; Marschke, K.B.; Crombie, D.L.; Jones, T.K.; Discovery and preliminary SAR studies of a novel, nonsteroidal progesterone receptor antagonist phamacophore. J Med Chem 1998, 41, 18, 3461. |
| 【2】 Jones, T.K.; Goldman, M.E.; Pooley, C.L.F.; Winn, D.T.; Edwards, J.E.; West, S.J.; Tegley, C.M.; Zhi, L.; Hamann, L.G.; Farmer, L.J.; Davis, R.J. (Ligand Pharmaceuticals, Inc.); Steroid receptor modulator cpds. and methods. EP 0800519; JP 1998510840; US 5688808; US 5688810; US 5693646; US 5693647; US 5696127; US 5696130; US 5696133; WO 9619458 . |
| 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) | 22531 | 4-Bromoaniline; 4-Bromophenylamine | 106-40-1 | C6H6BrN | 详情 | 详情 |
| (II) | 26570 | 6-bromo-2,2,4-trimethyl-1,2-dihydroquinoline | C12H14BrN | 详情 | 详情 | |
| (III) | 26571 | tert-butyl 6-bromo-2,2,4-trimethyl-1(2H)-quinolinecarboxylate | C17H22BrNO2 | 详情 | 详情 | |
| (IV) | 26572 | 1-(tert-butoxycarbonyl)-2,2,4-trimethyl-1,2-dihydro-6-quinolinylboronic acid | C17H24BNO4 | 详情 | 详情 | |
| (V) | 26575 | 1,3-dibromo-5-fluorobenzene | 1435-51-4 | C6H3Br2F | 详情 | 详情 |
| (VI) | 26576 | 3-bromo-5-fluorobenzonitrile | C7H3BrFN | 详情 | 详情 | |
| (VII) | 26577 | tert-butyl 6-(3-cyano-5-fluorophenyl)-2,2,4-trimethyl-1(2H)-quinolinecarboxylate | C24H25FN2O2 | 详情 | 详情 |