Acetonitrile → HCID 46215991, compound

Participants

Reaction Conditions

Reaction Steps

Into a 25 mL sealable tube under nitrogen were combined 4-{2-amino-6-[(1,1-dimethylethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile (500 mg, 1.25 mmol) and hydrazine monohydrate (1.22 mL) in EtOH (8 mL). The vial was sealed, and the reaction mixture was stirred at 95° C. for 22 hours. The solution was concentrated, partitioned between EtOAc and water, and extracted with EtOAC (2×) and CH2Cl2. The organic layer was separated, washed with NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The resulting solid was dissolved in a mixture of CH3CN/water/CH3OH/DMSO and purified on a Gilson RPHPLC (CH3CN/H2O w/0.1% TFA). Fractions were evaporated, aqueous potassium carbonate was added to the residue and the solution was stirred at room temperature for 2 hrs. The aqueous mixture was extracted with EtOAc (×2) and DCM (×2). The organic layer was separated, washed with brine, dried (MgSO4), filtered, concentrated and azeotroped with CH3CN to give a brown solid. Minimum amount of acetonitrile was added to the solids, and the resulting mixture was sonicated. A white precipitate crashed out which was filtered and washed with hexanes and Et2O to afford the title compound (102 mg) as a white solid. LC-MS (ES) m/z=298 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.42 (s, 9H), 5.36 (s, 2H), 5.90 (s, 2H), 6.31 (s, 1H), 6.53 (s, 1H), 7.36 (dd, J=8.6, 1.3 Hz, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.80 (s, 1H), 11.50 (s, 1H).

Provenance & Evidence