反应详情

A stirred suspension of guanidine hydrochloride (3.8 kg, 39.8 mol) and KOtBu (4.28 kg, 38.1 mol) in DME (17.6 L) was heated to reflux under N2 for 1 hour. The gum containing solution was cooled to room temperature, diluted with NMP (8.8 L) and 1,4-dichloro-7-(3-cyanophenyl)isoquinoline (4.4 kg, 14.7 mol) was added as a solid. The mixture was heated at reflux overnight, cooled to room temperature, filtered through a pad of celite and the pad washed with DME (4.4 L). Water (35.2 L) was added to the filtrate. The resultant slurry was stirred for 2 hour and the solid collected by filtration. The solid was washed with water (4.4 L) and dried in vacuo at 50° C. to give (4-chloro-7-(3-cyanophenyl)isoquinolin-1-yl)guanidine (4.55 kg, 14.1 mol, 96%) as a green solid.

1. temperaturewas heated
2. temperatureto reflux under N2 for 1 hour
3. additionThe gum containing solution
4. additionwas added as a solid
5. temperatureThe mixture was heated
6. temperatureat reflux overnight
7. temperaturecooled to room temperature
8. filtrationfiltered through a pad of celite
9. washthe pad washed with DME (4.4 L)
10. additionWater (35.2 L) was added to the filtrate
11. filtrationthe solid collected by filtration
12. washThe solid was washed with water (4.4 L)
13. customdried in vacuo at 50° C.