Trifluoroacetic acid → (6-Morpholin-4-ylpyrimidin-4-yl)hydrazine

Participants

Reaction Steps

A solution of 4,6 dichloropyrimidine (300 mg, 2 mmol), tert-butyl carbazate (280 mg, 2.1 mmol) and Hunig's base (453 μL, 2.6 mmol) in ethanol (3 ml) was stirred at 120° C. for 1 hour under microwave condition. After morpholine (700 μL, 8 mmol) was added, the mixture was then resubmitted to the same microwave condition for another hour. Evaporation of solvent under vacuum gave a white solid which was treated with TFA (3 ml) in DCM (3 ml) for 20 min. After evaporation of solvent, the residue was redissolved in methanol. Treatment with solid NaHCO3 removed the traces of TFA that might have been left over. Filtration followed by evaporation of the solvent gave a residue which was submitted to reverse-phase HPLC purification to produce (6-morpholin-4-yl-pyrimidin-4-yl)-hydrazine (200 mg, 1 mmol, 50% in 3 steps) as a white solid. MH+196. Alternatively, the same compound may be generated by stirring a solution of 4,6 dichloropyrimidine (300 mg, 2 mmol), morpholine (280 mg, 2.1 mmol) and diisopropylethylamine (453 μL, 2.6 mmol) in ethanol (3 ml) for one hour. After addition of hydrazine (370 μL, 6 mmol), the mixture was stirred at 120° C. for 1 hour under microwave condition. After evaporation of the solvent, the compound was dissolved in DMSO before submitted to prep HPLC purificaton which then gave 6-morpholin-4-yl-pyrimidin-4-yl)-hydrazine. MH+196.

Provenance & Evidence