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]=1Participants
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.
Workup
- temperaturethe mixture refluxed overnight
- concentrationThe reaction mixture was concentrated in vacuo
- additionthe residue treated with water
- extractionextracted with dichloromethane
- extractionThe dichloromethane extract
- dry with materialwas dried over magnesium sulphate
- concentrationconcentrated in vacuo
- customThe residue was purified
- customby purified by column chromatography on silica gel
- washeluting with DCM
Sources & evidence
- ORD record
- ord-d40d53423b204ae899cabd2c581aee9e
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07928099B2
Reaction notes
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