反应详情

A mixture of crude 3-methyl-2-oxo-1-(2-pyridinylmethyl)-4-imidazolidinecarboxylic acid (˜0.7 mmol), 1-hydroxybenzotriazole hydrate (113 mg, 0.84 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (161 mg, 0.84 mmol), and N-ethyl morpholine (0.27 ml, 2.1 mmol) in dichloromethane (20 ml)/N,N-dimethylformamide (2 ml) was stirred at room temperature for 10 minutes. A solution of [(2-chloro-3,4-difluorophenyl)methyl]amine (150 mg, 0.84 mmol) in dichloromethane (5 ml) was added and the reaction stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane and the solution was washed with saturated sodium hydrogen carbonate solution, water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 0-10% methanol in dichloromethane. The residue was triturated with ether/hexanes and the solid was dried. The residue was dissolved in dichloromethane (2 ml), hydrogen chloride (1M in ether, 0.1 ml) was added and the solvent was evaporated. The solid was co-evaporated with ethyl acetate and ether and then triturated with ether. The solid was collected and dried to give N-[(2-chloro-3,4-difluorophenyl)methyl]-3-methyl-2-oxo-1-(2-pyridinylmethyl)-4-imidazolidinecarboxamide hydrochloride (40 mg). LC/MS [M+H]+=395, retention time=1.85 minutes.

1. stirringthe reaction stirred at room temperature for 18 hours
2. washthe solution was washed with saturated sodium hydrogen carbonate solution, water and brine
3. customdried
4. customevaporated
5. customThe residue was purified by silica gel chromatography
6. washeluting with 0-10% methanol in dichloromethane
7. customThe residue was triturated with ether/hexanes
8. customthe solid was dried
9. dissolutionThe residue was dissolved in dichloromethane (2 ml)
10. additionhydrogen chloride (1M in ether, 0.1 ml) was added
11. customthe solvent was evaporated
12. customtriturated with ether
13. customThe solid was collected
14. customdried