反应详情

To a solution of COMPOUND 249 (65 mg, 0.21 mmol) in THF (2 mL) was added nicotinoyl chloride hydrochloride (60 mg, 0.34 mmol) followed by DIPEA (0.10 mL, 0.57 mmol). The resultant mixture was stirred at room temperature for 40 minutes. The mixture was treated with 1.0 N NaOH (5 mL) and extracted with CH2Cl2 (4×10 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. Purification of the crude material by radial chromatography on silica gel (1 mm plate, 20:1:1 CH2Cl2-MeOH—NH4OH) provided 75 mg (86%) of COMPOUND 265 as a white solid. 1H NMR (CDCl3) δ 1.61-1.75 (m, 2H), 1.90-1.99 (m, 2H), 2.09 (s, 6H), 2.55-3.00 (m, 3H), 3.75-3.90 (m, 5H), 4.75-4.80 (m, 1H), 7.09 (dd, 2H, J=7.5, 4.8 Hz), 7.34-7.39 (m, 3H), 7.75 (dt, 1H, J=6.0, 1.8 Hz), 8.35 (d, 2H, J=4.8 Hz), 8.65 (s, 2H); ES-MS m/z 416 (M+H).

1. extractionextracted with CH2Cl2 (4×10 mL)
2. dry with materialThe combined organic extracts were dried (Na2SO4)
3. concentrationconcentrated under reduced pressure
4. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, 20:1:1 CH2Cl2-MeOH—NH4OH)