Hydrazine hydrate (1:1) → HCID 58504813, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 2-fluoro-4-{2-(methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-6-(methylthio)benzonitrile (350 mg, 0.87 mmol) in ethanol (10 mL) was added hydrazine monohydrate (2.5 mL) in one portion. The resulting suspension was heated in an oil bath to 100° C. under a reflux condenser for 20 hours. LCMS showed complete conversion. The mixture was filtered through celite, and the filtrate was concentrated in vacuo. The residue was taken up in water (30 mL) and sonicated briefly. The resulting suspension was filtered. The collected solids underwent purification by silica gel column chromatography using gradient elution of 1% A in CHCl3 to 100% A (where A was a mixture of 800/80/3200 CH3OH/NH4OH/CHCl3). After removal of eluant solvents, the residue was redissolved in CHCl3, filtered, and concentrated in vacuo. The residue was taken up in water (15 mL) as a suspension. The solids formed were collected by filtration and dryed under vacuum at room temperature over P2O5 for 20 hours. These solids were washed with hexane (3×3 mL). Further drying under vacuum at 65° C. for 20 hours gave the title compound (282 mg) as a cream-colored solid. LC-MS (ES) m/z=414 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 0.89 (d, J=6.8 Hz, 3H), 1.11 (d, J=6.6 Hz, 3H), 2.45-2.55 (m, 1H), 2.65 (s, 3H), 2.96 (s, 3H), 3.25-3.35 (m, 1H), 3.53-3.61 (m, 2H), 3.94 (dd, J=11.2, 3.4 Hz, 1H), 4.11 (d, J=11.9 Hz, 1H), 6.40 (s, 1H), 7.40 (s, 1H), 7.62 (s, 1H).

Provenance & Evidence