Formaldehyde → HCID 73295629, compound

Participants

Reaction Steps

A mixture of 1-(2-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide 66 (0.081 g, 0.16 mmol) and formaldehyde (37 wt % in H2O; 36 μL, 0.49 mmol) in MeOH (5 mL) was stirred at room temperature for 10 minutes. Sodium triacetoxyborohydride (0.137 g, 0.649 mmol) was then added and stirring was continued for 3 hours at room temperature. The volatiles were removed in vacuo and sat. aq. NaHCO3 (20 mL) was added to the residue. The aqueous phase was extracted with EtOAc (3×20 mL) and the combined organics were washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The yellow residue was taken up in MeOH and loaded onto an SCX cartridge (10 g). The column was eluted with 5 column volumes of MeOH and then 5 column volumes of 2% v/v aqueous ammonia in MeOH to release the amine product. The solvent was evaporated under reduced pressure, the residue was taken up in DCM and a solid was precipitated by the addition of petroleum benzine 40-60° C. The solid was isolated by filtration and air dried to give the title compound 67 as a yellow solid (0.048 g, 58%). LCMS-A: rt 4.82 min; m/z 514 [M+H]+.

Provenance & Evidence