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

【结构式】

【分子编号】22137

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

【CA登记号】

【分子式】C₁₄H₁₅FN₂O₂

【分子量】262.2837832

【元素组成】C 64.11% H 5.76% F 7.24% N 10.68% O 12.2%

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：(III)

The reaction of 4-fluorophenylhydrazine hydrochloride (I) with N-carbethoxy-4-piperidone (II) under Fisher's conditions affords N2-carbethoxy-8-fluoro-2,3,4,5-tetrahydro-1H-pyridol[4,3-b]indole (III). Treatment of (III) with Claisen's alkali affords the N-2 unsubstituted 8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (IV), which is finally condensed with 3-pyridinylpropyl bromide hydrobromide (V) in DMF in the presence of triethyl amine (TEA). Compound (V) is obtained by refluxing 3-pyridinylpropanol with 48% hydrobromic acid.

参考文献中间体

合成目标

【1】 Andree, T.H.; Webb, M.B.; Patel, U.R.; Muth, E.A.; Moyer, J.A.; Abou-Gharbia, M.; Antipsychotic activity of substituted gamma-carbol. J Med Chem 1987, 30, 1818.
【2】 Andree, T.; Abou-Gharbia, M.; WY-47384. Drugs Fut 1988, 13, 6, 541.

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)	13486	Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone	29976-53-2	C₈H₁₃NO₃	详情	详情
(I)	22135	1-(4-fluorophenyl)hydrazine	371-14-2	C₆H₇FN₂	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)	14941	8-fluoro-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole	39876-39-6	C₁₁H₁₁FN₂	详情	详情
(V)	22139	3-(3-bromopropyl)pyridine		C₈H₁₀BrN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

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