反应详情

DIAD (95 μL, 0.491 mmol) was slowly added to a solution of 2-(2-{4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidin-1-yl}pyrimidin-5-yl)propan-2-ol (100 mg, 0.327 mmol), 1-(azetidin-1-yl)-2-(2-fluoro-4-hydroxyphenyl)ethanone (72 mg, 0.344 mmol), and triphenylphosphine (129 mg, 0.491 mmol) in DCM (1.6 mL). The mixture was stirred at rt for 3 hrs. The mixture was diluted with DCM (8 mL) and washed with 2 N NaOH solution (5 mL×1). The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC using 2×2000 micron silica preparative TLC plates (uv 254 active) which were developed using 100% EtOAc. The desired band (Rf=0.5 @ 100% EtOAc) was collected and extracted to give the title compound. 1H NMR (500 MHz, CD3CN) δ 8.41 (s, 2H), 7.17 (t, 1H), 6.72 (t, 2H), 4.68 (t, 2H), 4.19 (t, 2H), 4.06 (m, 2H), 3.91 (t, 211), 3.36 (s, 2H), 2.83 (t, 2H), 2.22 (m, 2H), 2.07 (m, 1H), 1.83 (m, 2H), 1.57 (m, 1H), 1.48 (s, 6H), 1.35-1.10 (m, 3H), 0.91 (m, 1H), 0.60 (m, 2H), −0.05 (m, 111). LC/MS (m/z): 497 (M+H)+, GPR119 Human EC50: 7.5 nM.

1. washwashed with 2 N NaOH solution (5 mL×1)
2. dry with materialThe organic phase was dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by preparative TLC
6. customThe desired band (Rf=0.5 @ 100% EtOAc) was collected
7. extractionextracted