Hydrazine hydrate (1:1) → 6-{2-Amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-{2-amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (355 mg, 1.04 mmol) in EtOH (10 mL) was added hydrazine monohydrate (2 mL) in one portion at room temperature. The mixture was heated in an oil bath at 100° C. under a gentle reflux for 18 hours. LCMS showed conversion complete. The mixture was cooled to room temperature, filtered through celite, and rinsed with EtOH (20 mL). The filtrate was concentrated in vacuo. The residue was suspended in water (10 mL). The suspension was sonicated briefly, and filtered. The solids were washed with water, dried under house vacuum at room temperature for 2 hours, and then under vacuum at room temperature over P2O5 for 20 hours. These solids were washed with hexane (2×3 mL), followed by drying under vacuum at 65° C. for 24 hours to give the title compound (256 mg) as a beige solid. LC-MS (ES) m/z=354 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 0.88 (d, J=6.8 Hz, 3H), 1.10 (d, J=6.6 Hz, 3H), 2.47-2.54 (m, 1H), 3.21-3.30 (m., 1H), 3.51-3.58 (m, 2H), 3.93 (dd, J=11.2, 3.41 Hz, 1H), 4.10 (d, J=11.6 Hz, 1H), 6.46 (s, 1H), 7.47 (dd, J=8.5, 1.4 Hz, 1H), 7.76 (d, J=8.6 Hz, 1H), 7.79 (s, 1H).

Provenance & Evidence