6-bromo-2,2,4-trimethyl-1,2-dihydroquinoline -Drug Synthesis Database

【结构式】

【分子编号】26570

【品名】6-bromo-2,2,4-trimethyl-1,2-dihydroquinoline

【CA登记号】

【分子式】C₁₂H₁₄BrN

【分子量】252.1539

【元素组成】C 57.16% H 5.6% Br 31.69% N 5.55%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

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. Lithium-halogen exchange in (III), followed by treatment with trimethyl borate provided boronic acid (IV). Subsequent Suzuki coupling of (IV) with 3-bromobenzonitrile (V) using tetrakis(triphenylphosphine)-palladium produced the 6-arylquinoline (VI). The Boc group of (VI) was finally removed with trifluoroacetic acid to furnish the title compound.

参考文献中间体

合成目标

【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)	26573	3-bromobenzonitrile	6952-59-6	C₇H₄BrN	详情	详情
(VI)	26574	tert-butyl 6-(3-cyanophenyl)-2,2,4-trimethyl-1(2H)-quinolinecarboxylate		C₂₄H₂₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

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.

参考文献中间体

合成目标

【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

Extended Information