Toluene → (+/-)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Participants

Reaction Conditions

Reaction Steps

A mixture of (±)-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-{2-chloro-5-[(4-ethyl-phenylamino)-methyl]-pyrimidin-4-yl}-amine (270 mg, 0.58 mmol) (from Example 39a supra) and triethylamine (0.25 mL, 1.76 mmol) (Allied Signal) in dichloromethane (6 mL) was cooled to 0° C. A 20% phosgene in toluene solution (0.32 mL, 0.61 mmol) (Fluka) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The mixture was allowed to warm up to room temperature and 4-(dimethylamino)pyridine (15 mg, 0.12 mmol) (Aldrich) was added. The reaction was stirred at room temperature overnight, heated at reflux for 4 hours, and then concentrated to dryness. The yellow residue was purified by flash chromatography (20% ethyl acetate in hexanes) to give (±)-1-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-7-chloro-3-(4-ethyl-phenyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 213 mg, 75%).

Provenance & Evidence