Phosphoric Acid → HCID 178458655, compound

Participants

Reaction Steps

To a solution of 5-chloro-N2-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (Example 6; 2.46 g, 6.28 mmol) in methanol (25 ml) was added a solution of phosphoric acid (85 wt % in water, 724 mg, 6.28 mmol) in methanol (10 ml). The resulting precipitate was heated to reflux and more methanol (25 ml) was added. The precipitate was allowed to stir at reflux for 1 hour before cooling down to room temperature. The solution was filtered and filter cake obtained was washed with methanol and transferred to a round bottomed-flask for recrystallization. A suspension of the salt in methanol (50 ml) was then heated to reflux. At reflux, methanol (125 ml) was added where dissolution occurred. The excess solvent was removed by distillation to a final volume of 75 ml. The flask was removed from the heat and the solution was allowed to cool to room temperature. The resulting precipitate was filtered, washed with methanol, and vacuum dried under N2 atmosphere (16 h) to afford 1.43 g (57% isolated yield) of the title compound. 1H NMR: 9.63 (s, 1H), 8.49 (s, 1H), 7.87-8.10 (m, 2H), 7.65 (t, J=8.67 Hz, 1H), 7.41 (dd, J=8.29, 4.52 Hz, 1H), 5.52 (s, 1H), 5.03 (br s, 1H), 4.65 (br s, 1H), 1.44 (d, J=6.78 Hz, 3H), 1.26 (d, J=6.03 Hz, 6H).

Provenance & Evidence