反应详情

To a stirred solution of 5-(methylsulfonyl)-2-(2-((1S,2R)-2-(piperidin-4-yl)cyclopropyl)ethoxy)pyridine (Step B, Example GJM10; 0.10 g, 0.32 mmol) in dichloromethane (3 mL) under a nitrogen atmosphere was added triethylamine (0.13 mL, 0.89 mmol) and neopentyl carbonochloridate (0.08 mL, 0.57 mmol). The resulting solution was stirred for 2 h at ambient temperature. The solution was diluted with saturated NH4Cl(aq.) (20 mL). The resulting layers were separated and the aqueous phase extracted with dichloromethane (3×15 mL). The combined organic extracts were washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification of the obtained residue by CombiFlash chromatography (12 g silica gel, 0 to 50% EtOAc in hexanes) provided the title compound as an off white semi-solid: 1H NMR (300 MHz, CDCl3) δ 8.72 (m, 1 h), 8.03 (m, 1H), 6.84 (m, 1H), 4.49 (m, 2H), 4.14 (m, 2H), 3.77 (s, 2H), 3.07 (s, 3H), 2.75 (m, 2H), 2.11 (m, 1H), 1.82-1.71 (m, 2H) 1.59-1.47 (m, 1H), 1.39-1.25 (m, 2H), 1.04-0.85 (m, 11H), 0.73-0.54 (m, 2H), −0.11 (q, J=4.8 Hz, 1H); MS (ESI) m/z 439 [M+H]+. GPR119 Human EC50: 2 nM

1. customThe resulting layers were separated
2. extractionthe aqueous phase extracted with dichloromethane (3×15 mL)
3. washThe combined organic extracts were washed with brine (20 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customPurification of the obtained residue by CombiFlash chromatography (12 g silica gel, 0 to 50% EtOAc in hexanes)