Sodium hydride → (S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((5-fluoro-2-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid

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Reaction Steps

To a solution of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.05 g, 0.086 mmol) and (S)-(5-fluoro-2-(pent-4-en-2-yloxy)phenyl)methanol (0.022 g, 0.103 mmol) in DMF (1 ml) was added sodium hydride (5.13 mg, 0.128 mmol) and the resulting yellow mixture was stirred at rt. After 5 h, the mixture was diluted with EtOAc and washed with 1N HCl followed by water and brine. The organic phase was dried (Na2SO4), filtered and concentrated. The oil was purified by flash chromatography (Biotage; 0%-10% MeOH/DCM; 10 CV) to give (S)-2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((5-fluoro-2-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid (20 mg, 0.031 mmol, 36.6% yield) was obtained as an amber oil. 1H NMR (400 MHz, CDCl3) δ 7.22 (dd, J=9.0, 2.9 Hz, 1H), 6.89 (dd, J=8.1, 3.2 Hz, 1H), 6.84-6.75 (m, 1H), 6.60 (s, 1H), 6.10-5.95 (m, 1H), 5.89-5.75 (m, 1H), 5.52-5.38 (m, 1H), 5.23-4.99 (m, 4H), 4.80 (s, 2H), 4.66 (s, 2H), 4.45-4.28 (m, 1H), 4.06-3.93 (m, 2H), 2.71-2.54 (m, 3H), 2.47 (d, J=5.9 Hz, 1H), 2.40-2.30 (m, 1H), 2.08-1.56 (m, 4H), 1.49-1.01 (m, 15H). LCMS (M+H) calcd for C35H48FN4O6: 639.35. found: 639.2.

Provenance & Evidence