反应详情

A mixture of crude 3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxylic acid (0.8 mmol), 1-hydroxybenzotriazole hydrate (147 mg, 0.96 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (184 mg, 0.96 mmol), and N-ethyl morpholine (0.307 ml, 2.4 mmol) in dichloromethane (15 ml) was stirred at room temperature for 10 minutes. A solution of {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (168 mg, 0.8 mmol) in dichloromethane (1 ml) was added and the reaction stirred at room temperature for 4 hours. The mixture was partitioned between dichloromethane and saturated sodium hydrogen carbonate solution. The organic phase was separated, washed with water and brine, dried and evaporated. The residue was purified by mass-directed automated HPLC. The solid was dissolved in methanol (5 ml) and anhydrous HCl in ether (1M, 0.5 ml) was added and the solution was evaporated. The resulting solid was collected, washed with ether and dried to give a pale yellow solid. The solid was dissolved in methanol and applied to a SCX ion exchange cartridge and washed with methanol and then 2M ammonia in methanol. The basic fractions were combined and evaporated and the resulting residue was triturated with ether, collected and dried to give N-{[2-Chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1-(3-pyridinyl)-4-imidazolidinecarboxamide (27 mg, 8%). LC/MS [M+H]+=413, retention time=1.96 minutes.

1. stirringthe reaction stirred at room temperature for 4 hours
2. customThe mixture was partitioned between dichloromethane and saturated sodium hydrogen carbonate solution
3. customThe organic phase was separated
4. washwashed with water and brine
5. customdried
6. customevaporated
7. customThe residue was purified
8. dissolutionThe solid was dissolved in methanol (5 ml)
9. additionanhydrous HCl in ether (1M, 0.5 ml) was added
10. customthe solution was evaporated
11. customThe resulting solid was collected
12. washwashed with ether
13. customdried
14. customto give a pale yellow solid
15. washwashed with methanol
16. customevaporated
17. customthe resulting residue was triturated with ether
18. customcollected
19. customdried