Benzamidine; benzenecarboximidamide -Drug Synthesis Database

【结构式】

【分子编号】37052

【品名】Benzamidine; benzenecarboximidamide

【CA登记号】

【分子式】C₇H₈N₂

【分子量】120.154

【元素组成】C 69.97% H 6.71% N 23.31%

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：(I)

The cyclization of benzamidine (I) with biacetyl (II) in water - isopropanol gives 4,5-dimethyl-2-phenylimidazoline-4,5-diol (III), which by treatment with refluxing aqueous 10% HCl is converted into 4-hydroxymethyl-2-phenyl-5-methylimidazole (IV). The reaction of (IV) with SOCl2 in refluxing benzene yields 4-chloromethyl-2-phenyl-5-methylimidazole (V), which is finally treated with NaCN in DMSO - water.

参考文献中间体

合成目标

【1】 Rasmussen, C.R.; 2-Aryl-4-cyanomethyl-5-methylimidazoles. DE 2528640; FR 2296627; FR 2309540; FR 2309541; GB 1502142; JP 51034159; US 4093811 .
【2】 Blancafort, P.; Hillier, K.; Serradell, M.N.; Castaner, J.; McN-2378. Drugs Fut 1982, 7, 4, 262.

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)	37052	Benzamidine; benzenecarboximidamide		C₇H₈N₂	详情	详情
(II)	37053	biacetyl	431-03-8	C₄H₆O₂	详情	详情
(III)	37054	4,5-dimethyl-2-phenyl-4,5-dihydro-1H-imidazole-4,5-diol		C₁₁H₁₄N₂O₂	详情	详情
(IV)	37055	(5-methyl-2-phenyl-1H-imidazol-4-yl)methanol		C₁₁H₁₂N₂O	详情	详情
(V)	37056	4-(chloromethyl)-5-methyl-2-phenyl-1H-imidazole		C₁₁H₁₁ClN₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Pyrimidinone (III) was formed by condensation of benzamidine hydrochloride (I) with diethyl (ethoxymethylene)malonate (II). Subsequent reaction with glycinamide derivative (V) in the presence of p-tosyl chloride and Et3N afforded the aminopyrimidine (VI) (1). Alternatively, aminopyrimidine (VI) was prepared by chlorination of pyrimidinone (III) with POCl3, followed by displacement of the resulting chloropyrimidine (IV) with glycinamide (V) (2). Basic hydrolysis of the ethyl ester group of (VI) furnished pyrimidinecarboxylic acid (VII). This was then subjected to a Curtius rearrangement employing diphenyl phosphoryl azide (DPPA) to produce the 8-oxopurine system (VIII). Finally, N-alkylation of (VIII) with iodomethane gave rise to the title compound.

参考文献中间体

合成目标

【1】 Masumoto, K.; et al.; SX-5216, highly potent and selective mitochondrial benzodiazepine receptor ligand as a potential anxiolytic agent. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 113.
【2】 Matsumoto, K.; Kondo, K.; Furukawa, K.; Murata, T.; Oka, M. (Dainippon Pharmaceutical Co., Ltd.); 2-Aryl-8-oxodihydropurine derivs., process for producing the same, medicinal compsns. containing the same, and intermediates thereof. EP 1036794; WO 9928320 .

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)	37052	Benzamidine; benzenecarboximidamide		C₇H₈N₂	详情	详情
(II)	14088	Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate	87-13-8	C₁₀H₁₆O₅	详情	详情
(III)	40809	ethyl 6-oxo-2-phenyl-1,6-dihydro-5-pyrimidinecarboxylate		C₁₃H₁₂N₂O₃	详情	详情
(IV)	40810	ethyl 4-chloro-2-phenyl-5-pyrimidinecarboxylate		C₁₃H₁₁ClN₂O₂	详情	详情
(V)	40811	2-amino-N-benzyl-N-ethylacetamide		C₁₁H₁₆N₂O	详情	详情
(VI)	40812	ethyl 4-([2-[benzyl(ethyl)amino]-2-oxoethyl]amino)-2-phenyl-5-pyrimidinecarboxylate		C₂₄H₂₆N₄O₃	详情	详情
(VII)	40813	4-([2-[benzyl(ethyl)amino]-2-oxoethyl]amino)-2-phenyl-5-pyrimidinecarboxylic acid		C₂₂H₂₂N₄O₃	详情	详情
(VIII)	40814	N-benzyl-N-ethyl-2-(8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide		C₂₂H₂₁N₅O₂	详情	详情

Extended Information