反应详情

To a solution of ethyl (2E)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridyl)acrylate (770 mg) in toluene (14 ml) was added 1-chloroethyl chloroformate (713 mg) at 23° C. and stirred at the same temperature for 1 hour. N,N-Diisopropylethylamine (0.348 ml) was added to the mixture, and the solution was stirred at 23° C. for 15 minutes. After it was concentrated under reduced pressure, the resulting residue was dissolved in EtOH (15 ml). The mixture was stirred at 65° C. for 30 minutes, and concentrated under reduced pressure. The residue was dissolved into EtOH (15 ml), and mixed with 2N-hydrogen chloride in EtOH solution (2 ml). The mixture was stirred at 86° C. for 5 hours. After it was concentrated under reduced pressure, the resulting residue was triturated with IPE (15 ml). Ethyl (2E)-3-{5-chloro-6-[(3R)-3-pyrrolidinylamino]-3-pyridyl}acrylate dihydrochloride (1.1 g) was obtained as brown syrup.

1. stirringthe solution was stirred at 23° C. for 15 minutes
2. concentrationAfter it was concentrated under reduced pressure
3. dissolutionthe resulting residue was dissolved in EtOH (15 ml)
4. stirringThe mixture was stirred at 65° C. for 30 minutes
5. concentrationconcentrated under reduced pressure
6. dissolutionThe residue was dissolved into EtOH (15 ml)
7. additionmixed with 2N-hydrogen chloride in EtOH solution (2 ml)
8. stirringThe mixture was stirred at 86° C. for 5 hours
9. concentrationAfter it was concentrated under reduced pressure
10. customthe resulting residue was triturated with IPE (15 ml)