Sodium hydride → (S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-bromo-4-(trifluoromethyl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

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Reaction Steps

To a solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(hydroxymethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.200 g, 0.421 mmol) and 2-bromo-1-(bromomethyl)-4-(trifluoromethyl)benzene (0.268 g, 0.843 mmol) in DMF (1 mL) was added sodium hydride (0.051 g, 1.264 mmol). The mixture was stirred at rt. After 30 min, the reaction was quenched with water and extracted with EtOAc (3×'s). The organic phases were combined and washed with brine, dried, filtered and concentrated. The residue was purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 25 CV) to give the title compound (0.200 g, 0.281 mmol, 66.7% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J=0.7 Hz, 1H), 7.73 (d, J=8.1 Hz, 1H), 7.59 (dd, J=8.6, 1.0 Hz, 1H), 6.59 (s, 1H), 6.02 (ddt, J=17.0, 10.4, 5.1 Hz, 1H), 5.95-5.85 (m, 1H), 5.53-5.39 (m, 1H), 5.19 (dd, J=10.5, 1.7 Hz, 1H), 4.87 (s, 2H), 4.77 (s, 2H), 4.30-4.14 (m, 2H), 4.02 (d, J=5.1 Hz, 2H), 2.62 (s, 3H), 2.06-1.61 (m, 3H), 1.35 (s, 3H), 1.25 (s, 12H) 5 piperidine protons not visible. LCMS (M+H) calcd for C33H43BrF3N4O5: 712.33. found: 713.4.

Provenance & Evidence