Hydrochloric Acid → HCID 71208757, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine (45.50 g, 150 mmol, 1.0 eq), (S)-pyrrolidin-3-ol (bought from CNH, 51.95 g, 277.5 mmol, 1.85 eq) and Ph3P (72.79 g, 277.5 mmol, 1.85 eq) in THF (400 mL) at rt was added DIAD (57.6 mL, 292.5 mmol, 1.95 eq) dropwise over 1.5 h. The mixture was stirred another 30 min and concentrated HCl solution (100 mL) was added dropwise over 30 min. The mixture was stirred overnight at rt. The mixture was then heated to 50° C. for 1 h to push the de-Boc to completion. THF was removed by rotavap. The crude was diluted with toluene and water. The aqueous solution was further washed with EtOAc and toluene. MeOH (70 mL, 10% v/v to the aqueous solution) was added followed by KOH solution (100 g in 100 ml, water). The mixture became warm and precipitate immediately formed. The mixture was cooled in a 4° C. fridge for 2 h and filtered. The solid was washed with water, air-dried and then dried under high-vac for 3 days. Yield 49.45 g (89%), HPLC purity 95%.

Provenance & Evidence