Diisopropylethylamine → (2R,3R)-3-(tert-butoxy)-2-((6-fluoro-2-(((S)-1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)amino)pyrimidin-4-yl)amino)butan-1-ol

Participants

Reaction Steps

A solution of (S)-4,6-difluoro-N-(1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)pyrimidin-2-amine (80 mg, 0.25 mmol), (2R,3R)-2-amino-3-(tert-butoxy)butan-1-ol (55 mg, 0.28 mmol, 1.1 equiv), and N-ethyl-N-isopropylpropan-2-amine (0.11 mL, 0.63 mmol, 2.5 equiv) in DMSO (1.3 mL) was heated at 85° C. for 16 hours. The reaction was cooled to room temperature and diluted with ethyl acetate (30 mL) and dilute aqueous sodium chloride (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane) provided (2R,3R)-3-(tert-butoxy)-2-((6-fluoro-2-(((S)-1-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)ethyl)amino)pyrimidin-4-yl)amino)butan-1-ol (0.058 g, white solid) in 50% yield. 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.66 (s, 1H), 7.61 (m, 2H), 7.13 (t, J=8.6 Hz, 2H), 5.35 (s, 1H), 5.30-5.14 (m, 2H), 5.04 (m, 1H), 3.94 (m, 1H), 3.77-3.65 (m, 2H), 1.57 (d, J=6.9 Hz, 3H), 1.21 (s, 9H), 1.15 (d, J=6.0 Hz, 3H). MS m/z 461.3 (M+H)+; Rt-0.88 min.

Provenance & Evidence