5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxamide -Drug Synthesis Database

【结构式】

【分子编号】33352

【品名】5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxamide

【CA登记号】

【分子式】C₁₅H₁₀ClFN₂O

【分子量】288.7083832

【元素组成】C 62.4% H 3.49% Cl 12.28% F 6.58% N 9.7% O 5.54%

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：(XVIII)

The hydrolysis of 3-(2-fluorophenyl)-5-chloroindole-2-carboxylate (XII) with KOH in refluxing ethanol affords the corresponding free acid (XVI), which by treatment with refluxing SOCl2 is converted into the acyl chloride (XVII). The reaction of (XVII) with NH3 in ether yields the amide (XVIII), which by N-alkylation with cyclopropylmethyl bromide (A) by means of NaH in DMF gives rise to the alkylated amide (VII) already obtained.

参考文献中间体

合成目标

【1】 Yamamoto, H.; et al.; ZA 6806061 .
【2】 Yamamoto, H.; et al. (Sumitomo Chemical Co., Ltd.); Process for producing benzodiazepine derivatives. US 3632574 .
【3】 Blancafort, P.; Serradell, M.N.; Castaner, J.; KB-509. Drugs Fut 1979, 4, 10, 720.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	22277	Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane	7051-34-5	C₄H₇Br	详情	详情
(VII)	33342	5-chloro-1-(cyclopropylmethyl)-3-(2-fluorophenyl)-1H-indole-2-carboxamide		C₁₉H₁₆ClFN₂O	详情	详情
(XII)	33347	ethyl 5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxylate		C₁₇H₁₃ClFNO₂	详情	详情
(XVI)	33350	5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxylic acid		C₁₅H₉ClFNO₂	详情	详情
(XVII)	33351	5-chloro-3-(2-fluorophenyl)-1H-indole-2-carbonyl chloride		C₁₅H₈Cl₂FNO	详情	详情
(XVIII)	33352	5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxamide		C₁₅H₁₀ClFN₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVIII)

The dehydration of the amide (XVIII) with refluxing POCl3 gives the corresponding nitrile (XIX), which by reduction with LiAlH4 in ether is converted into the 2-aminomethyl derivative (XX). The treatment of (XX) with CrO3 in acetic acid yields 5-(2-fluorophenyl)-7chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one (XXI) (1,10), which is finally N-alkylated with cyclopropylmethy bromide (A) by means of phenyllithium in THF.

参考文献中间体

合成目标

【1】 Yamamoto, H.; et al.; ZA 6806061 .
【2】 Okamoto, T.; et al.; Process for producing 1-substituted benzodiazepine derivatives. DE 2151540; FR 2110017; GB 1338106; NL 7114202; US 3832344 .
【3】 Yamamoto, H.; et al. (Sumitomo Chemical Co., Ltd.); Process for producing benzodiazepine derivatives. US 3632574 .
【4】 Blancafort, P.; Serradell, M.N.; Castaner, J.; KB-509. Drugs Fut 1979, 4, 10, 720.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	22277	Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane	7051-34-5	C₄H₇Br	详情	详情
(XVIII)	33352	5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxamide		C₁₅H₁₀ClFN₂O	详情	详情
(XIX)	33353	5-chloro-3-(2-fluorophenyl)-1H-indole-2-carbonitrile		C₁₅H₈ClFN₂	详情	详情
(XX)	33354	[5-chloro-3-(2-fluorophenyl)-1H-indol-2-yl]methanamine; [5-chloro-3-(2-fluorophenyl)-1H-indol-2-yl]methylamine		C₁₅H₁₂ClFN₂	详情	详情
(XXI)	33355	7-chloro-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one	2886-65-9	C₁₅H₁₀ClFN₂O	详情	详情

Extended Information