Water → 5-Fluoro-2-{4-[({5-[4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)methyl]-1-piperidinyl}pyrimidine

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-[4-(methylsulfonyl)phenyl]-2-pyrazinol (and tautomers thereof) (prepared as in Example 145, Step 2, 0.15 g, 0.60 mmol), [1-(5-fluoro-2-pyrimidinyl)-4-piperidinyl]methyl methanesulfonate (0.234 g, 0.81 mmol) and K2CO3 (0.17 g, 1.20 mmol) in DMF (6 mL) was stirred at 100° C. in a preheated oil bath for 2.5 h. The mixture was cooled to ambient temperature, treated with water, and the mixture was extracted with EtOAc (60 mL×2). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to give crude product as a light brown solid. The crude product was purified by chromatography on a silica gel column eluted with 1:30 acetone/CH2Cl2 then 1:20 acetone/CH2Cl2 to give 0.132 g (50%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H), 8.30 (s, 1H), 8.18 (s, 2H), 8.11 (d, 2H, J=8.0 Hz), 8.02 (d, 2H, J=8.1 Hz), 4.80-4.65 (m, 2H), 4.25 (d, 2H, J=6.6 Hz), 3.07 (s, 3H), 3.00-2.85 (m, 2H), 2.10-2.05 (m, 1H), 2.00-1.85 (m, 2H), 1.45-1.30 (m, 2H); LRMS (ESI), m/z 444 (M+H).

Provenance & Evidence