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

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.

1. waitthe mixture was then resubmitted to the same microwave condition for another hour
2. customEvaporation of solvent under vacuum
3. customgave a white solid which
4. customAfter evaporation of solvent
5. dissolutionthe residue was redissolved in methanol
6. customTreatment with solid NaHCO3 removed the traces of TFA that
7. waitmight have been left over
8. filtrationFiltration
9. customfollowed by evaporation of the solvent
10. customgave a residue which
11. customwas submitted to reverse-phase HPLC purification

ORD record

ord-b4be4797e1c24e899931caf5e1842fba

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07919528B2