Acetic Acid → (2S)-3-[4-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanamide

Participants

Reaction Conditions

Reaction Steps

2-Chloro-4-(difluoromethyl)pyrimidine (24.8 mg, 0.12 mmol) and acetic acid (0.0074 mL, 0.130 mmol) were added to an oven-dried flask containing (2S)-3-[4-(3-amino-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanamide (46.2 mg, 0.12 mmol) dissolved in dioxane (0.41 mL). The mixture was stirred for 3 hours at 120° C. The mixture was then cooled to room temperature, diluted with water, and extracted with EtOAc (3×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2 to 100% EtOAc/hexanes) to afford (2S)-3-[4-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanamide. MS ESI calcd. for C18H19F2N6O2 [M+H]+ 389. found 389. 1H NMR (500 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.68 (d, J=4.9 Hz, 1H), 7.96 (s, 1H), 7.82 (s, 1H), 7.76 (s, 1H), 7.37 (s, 1H), 7.34 (s, 1H), 7.32 (s, 1H), 7.04 (d, J=4.9 Hz, 1H), 7.01 (s, 1H), 6.87 (t, J=54.4 Hz, 1H), 5.86 (d, J=5.9 Hz, 1H), 4.41-4.33 (m, 1H), 4.24-4.18 (m, 1H), 4.17-4.13 (m, 1H), 2.28 (s, 3H).

Provenance & Evidence