4-(aminomethyl)benzonitrile -Drug Synthesis Database

【结构式】

【分子编号】47293

【品名】4-(aminomethyl)benzonitrile

【CA登记号】

【分子式】C₈H₈N₂

【分子量】132.165

【元素组成】C 72.7% H 6.1% N 21.2%

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：(XX)

In a further procedure, bromide (XV) was reacted with hexamethylenetetramine in refluxing EtOH followed by acid hydrolysis to produce the benzyl amine (XX). Mercapto imidazole (XXII) was then obtained by condensation of amine (XX) with dihydroxyacetone (XXI) and KSCN. Subsequent oxidative desulfuration gave the hydroxymethyl imidazole (XVIII). This was converted to the corresponding chloride (XXIII) by treatment with either SOCl2 in DMF or the Vilsmeier reagent. Finally, chloride (XXIII) was condensed with piperazinone (VIII) in the presence of diisopropylethylamine.

参考文献中间体

合成目标

【1】 Cowen, J.A.; Askin, D.; McWilliams, J.C.; Maligres, P.E.; McCauley, J.A. (Merck & Co., Inc.); Process for making farnesyl-protein transferase inhibitors. WO 0001691 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	47289	1-(3-chlorophenyl)-2-piperazinone		C₁₀H₁₁ClN₂O	详情	详情
(XV)	14200	4-(Bromomethyl)benzonitrile; alpha-Bromo-p-tolunitrile	17201-43-3	C₈H₆BrN	详情	详情
(XVIII)	38389	4-[[5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]benzonitrile		C₁₂H₁₁N₃O	详情	详情
(XX)	47293	4-(aminomethyl)benzonitrile		C₈H₈N₂	详情	详情
(XXI)	14575	Dihydroxyacetone; 1,3-dihydroxyacetone	96-26-4	C₃H₆O₃	详情	详情
(XXII)	47294	4-[[5-(hydroxymethyl)-2-sulfanyl-1H-imidazol-1-yl]methyl]benzonitrile		C₁₂H₁₁N₃OS	详情	详情
(XXIII)	47295	4-[[5-(chloromethyl)-1H-imidazol-1-yl]methyl]benzonitrile		C₁₂H₁₀ClN₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The N-protected dipeptide (I) is coupled to 4-(aminomethyl)benzonitrile (II) by means of EDC to afford amide (III). Acidic cleavage of the N-Boc group of (III) yields the deprotected amine (IV), which is then condensed with sulfamoyl chloride, producing sulfamide (V). From this, the target amidine can be obtained in two ways. Addition of hydrogen sulfide to the cyano group of (V), followed by S-alkylation with iodomethane, gives rise to the thioimidate (VI), which is then displaced with ammonium acetate to provide the desired amidine. Alternatively, addition of hydroxylamine to nitrile (V) leads to the amidoxime (VII) which, upon catalytic hydrogenation, is converted into the title amidine.

参考文献中间体

合成目标

【1】 Kwon, O.H.; Lee, S.H.; Park, H.D.; Jung, W.-H.; Lee, K.; Park, C.W.; Noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1. Bioorg Med Chem Lett 2002, 12, 7, 1017.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	58971	(2S)-1-{(2R)-2-[(tert-butoxycarbonyl)amino]-3,3-diphenylpropanoyl}-2-pyrrolidinecarboxylic acid	C₂₅H₃₀N₂O₅	详情	详情
(II)	47293	4-(aminomethyl)benzonitrile	C₈H₈N₂	详情	详情
(III)	58972		C₃₃H₃₆N₄O₄	详情	详情
(IV)	58973	(2S)-1-[(2R)-2-amino-3,3-diphenylpropanoyl]-N-(4-cyanobenzyl)-2-pyrrolidinecarboxamide	C₂₈H₂₈N₄O₂	详情	详情
(V)	58974	(2S)-1-{(2R)-2-[(aminosulfonyl)amino]-3,3-diphenylpropanoyl}-N-(4-cyanobenzyl)-2-pyrrolidinecarboxamide	C₂₈H₂₉N₅O₄S	详情	详情
(VI)	58975	methyl 4-({[((2S)-1-{(2R)-2-[(aminosulfonyl)amino]-3,3-diphenylpropanoyl}pyrrolidinyl)carbonyl]amino}methyl)benzenecarbimidothioate	C₂₉H₃₃N₅O₄S₂	详情	详情
(VII)	58976	(2S)-N-{4-[amino(hydroxyimino)methyl]benzyl}-1-{(2R)-2-[(aminosulfonyl)amino]-3,3-diphenylpropanoyl}-2-pyrrolidinecarboxamide	C₂₈H₃₂N₆O₅S	详情	详情

Extended Information