5-Bromo-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline -Drug Synthesis Database

【结构式】

【分子编号】10871

【品名】5-Bromo-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline

【CA登记号】

【分子式】C₁₀H₁₁BrFN

【分子量】244.1064832

【元素组成】C 49.2% H 4.54% Br 32.73% F 7.78% N 5.74%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

The bromination of 5-fluoro-2-methylquinoline (I) with Br2 and Ag2SO4 in H2SO4 or with Br2 and AlCl3 gives 5-bromo-6-fluoro-2-methylquinoline (II), which is reduced with H2 over PtO2 in acetic acid, yielding 5-bromo-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (III). The cyclization of (III) with diethyl ethoxymethylenemalonate (IV) and polyphosphoric acid (PPA) at 150 C affords 8-bromo-9-fluoro-5-methyl-1-oxo-6,7-dihydro-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid (V), which is finally condensed with 4-hydroxypiperidine (VI) by heating at 160 C in HMPT.

参考文献中间体

合成目标

【1】 Kano, M.; Nakagawa, K.; Ishikawa, H.; Uno, T. (Otsuka Pharmaceutical Co., Ltd.); Antibacterial agents. JP 1983090511 .
【2】 Bernauer, K.; Borgulya, J.; Bruderer, H.; Da Prada, M.; Zurcher, G. (F. Hoffmann-La Roche AG); 3,5-Disubstituted pyrocatechol derivs. EP 0237929; US 5389653; US 5476875 .
【3】 Ishikawa, H.; Tabusa, F.; Miyamoto, H.; Kano, M.; Ueda, H.; Tamaoka, H.; Nakagawa, K.; Synthesis of substituted 6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acids. Chem Pharm Bull 1989, 37, 8, 2103-8.
【4】 Prous, J.; Castaner, J.; OPC-7251. Drugs Fut 1990, 15, 7, 685.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情
(I)	10869	6-Fluoro-2-methylquinoline	1128-61-6	C₁₀H₈FN	详情	详情
(II)	10870	5-Bromo-6-fluoro-2-methylquinoline		C₁₀H₇BrFN	详情	详情
(III)	10871	5-Bromo-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline		C₁₀H₁₁BrFN	详情	详情
(IV)	10872	diethyl 2-[(E)-ethoxymethylidene]succinate		C₁₁H₁₈O₅	详情	详情
(V)	10873	8-Bromo-9-fluoro-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid		C₁₄H₁₁BrFNO₃	详情	详情

Extended Information