Potassium tert-butoxide → 1-(azetidin-1-yl)-2-[6-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)pyridin-3-yl)ethanone

Participants

Reaction Steps

2-((1S,2R)-2-(1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol (40 mg, 0.145 mmol) was dissolved in DMF (2 ml) at RT under N2 and potassium tert-butoxide (0.218 ml, 0.218 mmol) was added. The mixture was stirred at RT for 5 min and 1-(azetidin-1-yl)-2-(6-chloropyridin-3-yl)ethanone (36.7 mg, 0.174 mmol) was added. The mixture was microwaved at 100° C. for 30 min. and 150° C. for 30 min. The mixture was diluted with CH3CN, filtered and purified by reverse-phase HPLC (SunFire Prep C18 OBD Sum 19×100 mm column; 25-95% acetonitrile in 0.1% formic acid in water gradient) to afford the title compound. 1H NMR (500 MHz, CDCl3) δ 8.10 (s, 2H), 8.01 (s, 1H), 7.61 (d, 1H), 6.75 (d, 1H), 4.70 (m, 2H), 4.39 (t, 2H), 4.21 (t, 2H), 4.03 (t, 2H), 3.38 (s, 2H), 2.85 (m, 2H), 2.45 (m, 2H), 2.31 (m, 2H), 2.18 (m, 1H), 1.84 (m, 2H), 1.58 (m, 1H), 1.40 (m, 2H), 1.10-1.20 (m, 5H), 0.95 (m, 2H), 0.68 (m, 2H), −0.40 (m, 1H). LC/MS (m/z): 450 (M+H)+, GPR119 Human EC50: 7.4 nM.

Provenance & Evidence