ethyl 8-fluoro-5-(4-fluorophenyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】60777

【品名】ethyl 8-fluoro-5-(4-fluorophenyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate

【CA登记号】

【分子式】C₂₀H₁₈F₂N₂O₂

【分子量】356.3720064

【元素组成】C 67.41% H 5.09% F 10.66% N 7.86% O 8.98%

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：(V)

The cyclization of p-fluorophenylhydrazine (I) with 1-carbethoxy-4-piperidinone (II) in refluxing ethanol gives 2-carbethoxy-8-fluoro-1,2,3,4-tetrahydro-gamma-carboline (III), which is arylated with p-fluorobromobenzene (IV), by means of Na2CO3 - Cu2Br2 in N-methyl-2-pyrrolidinone heated at 200 C to yield 2-carbethoxy-8-fluoro-5-(p-fluorophenyl)-1,2,3,4-tetrahydro-gamma-carboline (V). The hydrolytic decarboxylation of (V) with KOH in refluxing ethanol affords 8-fluoro-5-(p-fluorophenyl)-1,2,3,4-tetrahydro-gamma-carboline (VI), which is alkylated with p-fluoro-gamma-bromobutyrophenone (VII) by means of Na2CO3 in hot DMF to give 8-fluoro-5-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-oxobutyl]-1,2,3,4-tetrahydro-gamma-carboline (VIII). Finally this compound is reduced with NaBH4 in ethanol - THF

参考文献中间体

合成目标

【1】 Harbert, C.A.; et al.; Neuroleptic activity in 5-aryl-tetrahydro-gamma-carbolines. J Med Chem 1980, 23, Suppl. 3, 635.
【2】 Plattner, J.J.; et al. (Pfizer Inc.); US 4001263 .
【3】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Leeson, P.A.; Mealy, N.E.; Flutroline. Drugs Fut 1981, 6, 2, 84.

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)	22135	1-(4-fluorophenyl)hydrazine	371-14-2	C₆H₇FN₂	详情	详情
(II)	13486	Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone	29976-53-2	C₈H₁₃NO₃	详情	详情
(III)	22137	ethyl 8-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate		C₁₄H₁₅FN₂O₂	详情	详情
(IV)	29012	1-bromo-4-fluorobenzene	460-00-4	C₆H₄BrF	详情	详情
(V)	60777	ethyl 8-fluoro-5-(4-fluorophenyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate		C₂₀H₁₈F₂N₂O₂	详情	详情
(VI)	60775	8-fluoro-5-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole		C₁₇H₁₄F₂N₂	详情	详情
(VII)	60778	4-bromo-1-(4-fluorophenyl)-1-butanone		C₁₀H₁₀BrFO	详情	详情
(VIII)	60779	4-[8-fluoro-5-(4-fluorophenyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]-1-(4-fluorophenyl)-1-butanone		C₂₇H₂₃F₃N₂O	详情	详情

Extended Information