Sodium ethoxide → 7-Benzyl-2-(4-methylbenzyl)-3,5,6,7,8,9-hexahydro-4H-pyrimido[4,5-d]azepin-4-one

Reaction equation

Cl.[CH3:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](=[NH:12])[NH2:11])=[CH:5][CH:4]=1.Cl.[CH2:14]([N:21]1[CH2:27][CH2:26][C:25](=O)[CH:24]([C:29](OCC)=[O:30])[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[O-]CC.[Na+]>>[CH2:14]([N:21]1[CH2:22][CH2:23][C:24]2[C:29](=[O:30])[NH:12][C:10]([CH2:9][C:6]3[CH:5]=[CH:4][C:3]([CH3:2])=[CH:8][CH:7]=3)=[N:11][C:25]=2[CH2:26][CH2:27]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

Reactant 3

HCID 2723922Sodium ethoxide

HCID 134308192-(4-Methylphenyl)ethanimidamide hydrochloride

HCID 67097548Ethyl 1-benzyl-5-oxoazepane-4-carboxylate hydrochloride

Product 1

HCID 1360580937-Benzyl-2-(4-methylbenzyl)-3,5,6,7,8,9-hexahydro-4H-pyrimido[4,5-d]azepin-4-oneYield 43%

Procedure

Under nitrogen, 2-(4-methylphenyl)ethanimidamide hydrochloride (360 mg, 1.95 mmol) and ethyl 1-benzyl-5-oxoazepane-4-carboxylate hydrochloride (500 mg, 1.61 mmol) were added to a freshly-prepared solution of sodium ethoxide (from sodium (120 mg, 5.22 mmol) dissolved in ethanol (15 ml)) and the mixture refluxed overnight. The reaction mixture was concentrated in vacuo and the residue treated with water. The mixture was acidified with 2M HCl solution, then rebasified using saturated aqueous NaHCO3 solution and extracted with dichloromethane. The dichloromethane extract was dried over magnesium sulphate and concentrated in vacuo. The residue was purified by purified by column chromatography on silica gel, eluting with DCM:MeOH, 98:2 to 94:6, to afford the title compound as a solid in 43% yield, 250 mg.