5-chloro-1-(4-fluorophenyl)-1H-indole -Drug Synthesis Database

【结构式】

【分子编号】59582

【品名】5-chloro-1-(4-fluorophenyl)-1H-indole

【CA登记号】

【分子式】C₁₄H₉ClFN

【分子量】245.6833032

【元素组成】C 68.44% H 3.69% Cl 14.43% F 7.73% N 5.7%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

Decarbomethoxylation of the known 3-hydroxyindole-2-carboxylate (I) in the presence of magnesium chloride in NMP at 160 C afforded indolinone (II), which was subsequently reduced with NaBH4 to the 3-hydroxy indoline (III). Dehydration of (III) by means of trifluoroacetic acid furnished indole (IV).

参考文献中间体

合成目标

【1】 Bogeso, K.P.; Hyttel, J.; Sanchez, C.; Arnt, J.; Perregaard, J.; Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles. J Med Chem 1992, 35, 6, 1092.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	59579	methyl 5-chloro-1-(4-fluorophenyl)-3-hydroxy-1H-indole-2-carboxylate	C₁₆H₁₁ClFNO₃	详情	详情
(II)	59580	5-chloro-1-(4-fluorophenyl)-1,2-dihydro-3H-indol-3-one	C₁₄H₉ClFNO	详情	详情
(III)	59581	5-chloro-1-(4-fluorophenyl)-3-indolinol	C₁₄H₁₁ClFNO	详情	详情
(IV)	59582	5-chloro-1-(4-fluorophenyl)-1H-indole	C₁₄H₉ClFN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

In an alternative method, Ullmann arylation of potassium N-(4-fluorophenyl)glycinate (VI) with potassium 2,5-dichlorobenzoate (V) afforded the N,N-diaryl glycine (VII). Cyclization of diacid (VII) in refluxing Ac2O produced the 3-acetoxy indole (VIII). This was then reduced to indole (IV) with NaBH4 in refluxing EtOH.

参考文献中间体

合成目标

【1】 Perregaard, J.K.; Costall, B. (H. Lundbeck A/S); Piperidyl-substd. indoles. EP 0533824; JP 1993509080; US 5439922; WO 9200070 .
【2】 Bech Sommer, M. (H. Lundbeck A/S); Method of manufacturing sertindole. WO 9851685 .
【3】 Bogeso, K.P.; Hyttel, J.; Sanchez, C.; Arnt, J.; Perregaard, J.; Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles. J Med Chem 1992, 35, 6, 1092.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	59582	5-chloro-1-(4-fluorophenyl)-1H-indole	C₁₄H₉ClFN	详情	详情
(V)	59583	potassium 2,5-dichlorobenzoate	C₇H₃Cl₂KO₂	详情	详情
(VI)	59584	potassium 2-(4-fluoroanilino)acetate	C₈H₇FKNO₂	详情	详情
(VII)	59585	2-[(carboxymethyl)-4-fluoroanilino]-5-chlorobenzoic acid	C₁₅H₁₁ClFNO₄	详情	详情
(VIII)	59586	5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl acetate	C₁₆H₁₁ClFNO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X). This was alkylated with 1-(2-chloroethyl)imidazolinone (XII), (prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII). The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).

参考文献中间体

合成目标

【1】 Perregaard, J.K. (H. Lundbeck A/S); Heterocyclic cpds.. AU 8655901; EP 0200322; ES 8707499; JP 1986236764; US 4710500 .
【2】 Perregaard, J.K.; Costall, B. (H. Lundbeck A/S); Piperidyl-substd. indoles. EP 0533824; JP 1993509080; US 5439922; WO 9200070 .
【3】 Bech Sommer, M. (H. Lundbeck A/S); Method of manufacturing sertindole. WO 9851685 .
【4】 Bogeso, K.P.; Hyttel, J.; Sanchez, C.; Arnt, J.; Perregaard, J.; Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles. J Med Chem 1992, 35, 6, 1092.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	59582	5-chloro-1-(4-fluorophenyl)-1H-indole		C₁₄H₉ClFN	详情	详情
(IX)	18178	4,4-piperidinediol	73390-11-1	C₅H₁₁NO₂	详情	详情
(X)	59587	5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole		C₁₉H₁₆ClFN₂	详情	详情
(XI)	59588	1-(2-hydroxyethyl)-2-imidazolidinone	3699-54-5	C₅H₁₀N₂O₂	详情	详情
(XII)	21329	1-(2-chloroethyl)-2-imidazolidinone	2387-20-4	C₅H₉ClN₂O	详情	详情
(XIII)	59589	1-{2-[4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-3,6-dihydro-1(2H)-pyridinyl]ethyl}-2-imidazolidinone	106516-54-5	C₂₄H₂₄ClFN₄O	详情	详情

Extended Information