反应详情

To a suspension of 3-methyl-2-oxo-1-[6-(trifluoromethyl)-4-pyrimidinyl]-4-imidazolidinecarboxylic acid (200 mg, 0.612 mmol) and N-ethylmorpholine (0.465 ml, 3.67 mmol) in dichloromethane (10 ml)/DMF (1 ml) was added 1-hydroxybenzotriazole hydrate (113 mg, 0.735 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (117 mg, 0.612 mmol) and the reaction mixture was stirred for 1 hour at room temperature. 1-(2-Chloro-3,4-difluorophenyl)methanamine (131 mg, 0.612 mmol) was then added and the reaction stirred overnight. Additional 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (117 mg, 0.612 mmol) was added and the reaction mixture was stirred for 3 hours. The reaction mixture was diluted with dichloromethane and washed with saturated sodium hydrogen carbonate solution, water, 3N citric acid solution, water then brine and separated through a hydrophobic frit and the organic layer concentrated under vacuum. The residue was purified by SP4 automated silica gel chromatography eluting with 10-100% ethyl acetate in isohexane to give N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-1-[6-(trifluoromethyl)-4-pyrimidinyl]-4-imidazolidinecarboxamide (95 mg, 33.8% yield). LC/MS [M+H]+=450, retention time=2.93 minutes.

1. stirringthe reaction stirred overnight
2. stirringthe reaction mixture was stirred for 3 hours
3. washwashed with saturated sodium hydrogen carbonate solution, water, 3N citric acid solution, water
4. custombrine and separated through a hydrophobic frit
5. concentrationthe organic layer concentrated under vacuum
6. customThe residue was purified by SP4 automated silica gel chromatography
7. washeluting with 10-100% ethyl acetate in isohexane