Ether hydrochloride → (2-Fluoro-4-methanesulfonyl-phenyl)-{6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-5-methyl-pyrimidin-4-yl}-amine

Participants

Reaction Steps

A mixture of (6-chloro-5-methyl-pyrimidin-4-yl)-(2-fluoro-4-methanesulfonyl-phenyl)-amine (HCl salt, 1.76 g, 5.0 mmol) and 1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-ol (1.05 g, 5.0 mmol) in anhydrous THF (10 mL) was treated with potassium t-butoxide (20 mL, 20 mmol), placed under inert atmosphere, and refluxed for 4 hours, at which point the reaction had stalled at 60% conversion. The reaction mixture was cooled, quenched with water (30 mL), and extracted with ether (2×50 mL). The combined organic extract was rinsed with water (20 mL), followed by brine (20 mL), and was dried over MgSO4. After solvent removal, the residue was rinsed with boiling ether (2×20 mL), and the combined rinses were set aside to cool. Crystallization yielded a white solid (91% pure by LCMS) which was triturated in hot ether and filtered hot to furnish Compound A93 as a white solid in >95% purity (731 mg, 30% yield). This material was taken up in CH2Cl2 (10 mL), to which was added 1 N HCl/ether (1.5 mL). Upon solvent removal, a light gray foam was obtained (800 mg): 1H NMR (DMSO-d6) δ 10.26 (brs, 1 H), 8.77 (s, 1 H), 8.22 (s, 1 H), 7.83-7.71 (m, 3 H), 5.33 (m, 1 H), 3.75 (m, 2 H), 3.57 (m, 2 H), 3.37 (s, 3 H), 2.83 (m 1 H), 2.13 (s, 3 H), 2.04 (m, 2 H), 1.78 (m, 2 H), 1.20 (d, 6 H, J=6.9 Hz), MS m/z 491.2 (M+).

Provenance & Evidence