5-Amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxamide → tert-butyl 3-(3-(3-methyl-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)piperidin-1-yl)azetidine-1-carboxylate

Participants

Reaction Steps

Into a 100-mL 3-necked round-bottom flask, was placed a solution of Na (128 mg, 5.57 mmol, 6.00 equiv) in ethanol (10 mL) at room temperature. To the resulting mixture was then added a solution of 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxamide (200 mg, 0.93 mmol, 1.00 equiv) in C4H10O (10 mL), in portions at room temperature, followed by a solution of methyl 1-(1-(tert-butoxycarbonyl)azetidin-3-yl)piperidine-3-carboxylate (1.66 g, 5.57 mmol, 6.00 equiv) in C4H10O (20 mL), in portions at room temperature. The resulting solution was heated to reflux overnight. The reaction was then quenched by the addition of water (20 mL). The resulting solution was extracted with DCM (3×30 mL) and the organic layers combined. The resulting mixture was washed with sodium chloride (2×30 mL). The mixture was dried over anhydrous sodium sulfate, the solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (50:1) to yield tert-butyl 3-(3-(3-methyl-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)piperidin-1-yl)azetidine-1-carboxylate as a yellow solid.

Provenance & Evidence