4-Fluorobenzyl chloride → HCID 89471767, compound

Participants

Reaction Conditions

Reaction Steps

4-Fluorobenzyl chloride (15 μl, 0.12 mmol) was added to a solution of N-((1-(2-(3-(1H-pyrazol-1-yl)phenyl)pyrimidin-4-yl)piperidin-4-yl)methyl)-3-hydroxy-5-methoxybenzamide (Example 13, 55 mg, 0.11 mmol) and cesium carbonate (80 mg, 0.24 mmol) in DMF (1 ml). The reaction mixture was heated to 40° C. for 5 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate and the combined organics were filtered through a hydrophobic frit and concentrated under reduced pressure. The crude residue was purified by normal phase chromatography, eluting with iso-hexane and increasing amounts of ethyl acetate to give the title compound N-((1-(2-(3-(1H-pyrazol-1-yl)phenyl)pyrimidin-4-yl)piperidin-4-yl)methyl)-3-(4-fluorobenzoxy)-5-methoxybenzamide as a white solid (42.5 mg). 1H NMR (CDCl3): δ 8.64 (1H, t, J=1.88 Hz), 8.34-8.29 (2H, m), 8.06 (1H, d, J=2.48 Hz), 7.86 (1H, ddd, J=8.02, 2.33, 1.07 Hz), 7.74 (1H, d, J=1.74 Hz), 7.54 (1H, t, J=7.90 Hz), 7.43-7.37 (2H, m), 7.11-7.05 (2H, m), 6.96 (1H, t, J=1.75 Hz), 6.91 (1H, t, J=1.74 Hz), 6.65 (1H, t, J=2.25 Hz), 6.49-6.44 (2H, m), 6.21 (1H, t, J=6.08 Hz), 5.04 (2H, s), 4.60 (2H, s), 3.82 (3H, s), 3.39 (2H, t, J=6.43 Hz), 3.01-2.92 (2H, m), 2.04-1.88 (3H, m), 1.33 (2H, qd, J=12.28, 4.12 Hz).

Provenance & Evidence