Hydrazine hydrate (1:1) → HCID 58504643, compound

Participants

Reaction Steps

A stock solution of sodium ethoxide in ethanol was generated by the addition of ethanol (20 mL) to NaH (254 mg, 10.56 mmol), followed by stirring at room temperature for 30 minutes. To a 20-mL microwave vial was added 4-{2-amino-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-2,6-difluorobenzonitrile (700 mg, 2.11 mmol), DMF (2 mL), and ethanol (3 mL). The reaction was cooled to 0° C., and a solution of sodium ethoxide in ethanol (4.40 mL, 2.324 mmol) was added. The reaction was stirred overnight, and an additional portion of DMF was added, and the reaction was allowed to stir overnight at room temperature. An additional 0.25 equiv of sodium ethoxide in ethanol (1 mL) was added and the reaction was stirred for 8 hours. The reaction mixture was poured into NH4Cl (sat.) and water (1:1, 30 mL) and extracted with EtOAc (3×100 mL). The combined organics were dried over Na2SO4 and concentrated. The residue was dissolved in ethanol (10 mL), and hydrazine hydrate (0.73 mL, 12.7 mmol) and Hunig's base (1.11 mL, 6.34 mmol) were added. The reaction was heated in a microwave reactor for 90 minutes at 150° C. The reaction was allowed to cool to room temperature, concentrated, and the resulting precipitate collected by filtration, washed with ethanol and dried in vacuo to afford the title compound (400 mg) as a white solid. LC-MS (ES) m/z=370 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.18 (d, J=6.6 Hz, 3H), 1.45 (t, J=7.0 Hz, 3H), 3.05-3.15 (m, 1H), 3.38-3.49 (m, 1H), 3.54-3.65 (m, 1H), 3.66-3.78 (m, 1H), 3.88-3.96 (m, 1H), 4.08 (d, J=12.6 Hz, 1H), 4.21 (q, J=6.8 Hz, 2H), 4.50 (d, J=4.8 Hz, 1H), 5.00 (s, 2H), 6.10 (s, 2H), 6.49 (s, 1H), 6.91 (s, 1H), 7.49 (s, 1H), 11.53 (s, 1H).

Provenance & Evidence