反应详情

A solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt (350 mg, 0.71 mmol), 2-hydroxyisobutyric acid (111 mg, 1.07 mmol), EDCI (327 mg, 1.7 mmol, HOBt (230 mg, 1.7 mmol) and DIPEA (0.36 mL, 2.13 mmol) was stirred at RT for 5 h before the addition of saturated aqueous sodium bicarbonate. The resultant mixture was extracted with DCM (2×30 mL), the combined extracts washed with brine then dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 5% MeOH in DCM) then freeze dried to give 227 as a white solid (141 mg, 43%). 1H NMR δ (ppm) (DMSO-d): 8.31 (1H, d, J=8.29 Hz), 7.82 (1H, s), 7.78 (1H, s), 7.03 (1H, d, J=8.38 Hz), 6.90 (1H, s), 5.85-5.77 (1H, m), 4.69 (2H, d, J=13.25 Hz), 4.48 (4H, t, J=7.99 Hz), 2.91-2.74 (4H, m), 1.85 (2H, d, J=13.04 Hz), 1.63-1.49 (2H, m), 1.49 (6H, d, J=6.64 Hz), 1.37 (6H, s). LCMS: RT=3.92 min, M+H+=465

1. extractionThe resultant mixture was extracted with DCM (2×30 mL)
2. washthe combined extracts washed with brine
3. dry with materialthen dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customthen freeze dried