Potassium Carbonate → 4-((4-Amino-6-chloropyrimidin-2-yl)amino)benzonitrile

Participants

Reaction Conditions

Reaction Steps

1500 ml of phosphorus oxychloride and 300 g of 4-(4-Amino-6-hydroxypyrimidin-2-ylamino)benzonitrile at 27±3° C. were added to the reaction vessel and heated to 97±3° C.; and maintained at same temperature for 7 hrs. After completion of the reaction, ˜50% of phosphorous oxychloride was distilled off under vacuum at 83±2° C. and the reaction mixture was cooled to 30±5° C. In a clean RB flask were added 1000 g of ice and 1000 mL of water and such was slowly added the above obtained reaction mass. The pH of the reaction mass was adjusted to 9.0±0.5 with 50% potassium carbonate solution in water at 5±5° C. The reaction mixture was stirred, filtered and the obtained solid was washed with 600 ml of water and suck dried. The wet solid was charged into a RB flask at 27±3° C. to which was added 600 ml of water. The resulting wet solid was taken into a RB flask and 600 ml of water was added, stirred, and filtered. The obtained solid was washed with water and suck dried. 3000 ml of ethyl acetate was charged into a RB flask and to this was added the obtained solid and heated to 43±3° C. The reaction mass was stirred for 20 mins and filtered hot. The residue was washed with ethyl acetate and filtrate (1) collected at 27±3° C. The obtained solid was again taken in RB flask to which was added 1500 ml of ethyl acetate and heated to 43±3° C., stirred and the hot reaction mass filtered and the filtrate (2) collected. Both filtrates (1) and (2) were taken and distilled off solvent at 47±3° C. To the residue was added 900 ml of heptane and cooled to 27±3° C. and was again added 1100 ml of heptane, stirred, the solid filtered and suck dried, and the solid was washed with heptane. The obtained solid was dried under vacuum. To the obtained 190 g of crude was added 380 ml of dimethyl formamide and 20.4 ml of 1,8-diazabicycloundec-7-ene under stirring at 27±3° C. and the reaction mass heated to 47±3° C. To the obtained clear solution was added 760 ml of water and stirred for 1 hr. The reaction mass was cooled and filtered. The solid was washed with 760 mL of water twice and suck dried. The solid was washed with 48 ml of chilled methanol and the solid suck dried. The obtained solid was further dried under vacuum to yield the title compound.

Provenance & Evidence