反应详情

[2-Fluoro-4-(2-{(1S,2R)-2-[1-(5-methoxypyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)phenyl]acetic acid (80 mg, 0.186 mmol), 1-hydroxybenzotriazole hydrate (42.8 mg, 0.279 mmol), 3-hydroxyazetidine hydrochloride (30.6 mg, 0.279 mmol) and (E)-3-(ethyldiazenyl)-N,N-dimethylpropan-1-amine hydrochloride (50.2 mg, 0.279 mmol) were dissolved in CH2Cl2 (4 ml). The mixture was stirred at RT for 5 min. and triethylamine (0.078 ml, 0.556 mmol) was added. The mixture was stirred at RT overnight and loaded directly on Preparative TLC that was developed with pure EtOAc. The desired product (Rf=0.35 @ pure EtOAc) was collected to give the title compound. 1H NMR (500 MHz, CDCl3) δ 8.1 (s, 2H), 7.21 (m, 1H), 6.65 (m, 2H), 4.60 (m, 3H), 4.30 (m, 2H), 4.05 (m, 3H), 3.90 (m, 1H), 3.80 (s, 3H), 3.72 (s, broad, 1H), 3.41 (s, 2H), 2.83 (m, 2H), 2.15 (m, 1H), 2.05 (s, broad, 1H), 1.92 (m, 2H), 1.55 (m, 1H), 1.40 (m, 2H), 0.95 (m, 2H), 0.68 (m, 2H), −0.40 (m, 1H). LC/MS (m/z): 485 (M+H)+. GPR119 Human EC50: 2.1 nM.

1. stirringThe mixture was stirred at RT overnight
2. customThe desired product (Rf=0.35 @ pure EtOAc) was collected