反应详情

To a slurry of N-(8-{[(2R)-2-hydroxy-3-(pyrrolidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)amine (0.250 g, 0.70 mmol) and nicotinic acid (0.107 g, 0.87 mmol, 1.3 equiv.) in DMF (10 mL) was added PyBOP (0.452 g, 0.87 mmol, 1.3 equiv.) followed by diisopropylethylamine (0.48 mL, 2.78 mmol, 4.0 equiv.). The resulting mixture was stirred at room temperature. After a few hours the mixture turned to a clear solution. The resulting solution was stirred at room temperature for 24 h, then was concentrated under reduced pressure. The residue was separated between water (25 mL) and a 4:1 CH2Cl2/isopropanol solution (50 mL). The resulting organic phase was washed with a saturated sodium bicarbonate solution, dried (anh. sodium sulfate) and concentrated under reduced pressure. The resulting material (0.588 g) purified using MPLC to afford N-(8-{[(2R)-2-hydroxy-3-(pyrrolidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide (0.16 g, 50%): HPLC ret. time 1.00 min.; 1H NMR (DMSO-d6+1 drop TFA-d) δ 1.83-1.93 (m, 2H), 1.93-2.05 (m, 2H), 3.04-3.15 (m, 2H), 3.29-3.34 (m, 2H), 3.53-3.62 (m, 2H), 4.03 (s, 3H), 4.20-4.32 (m, 5H), 4.53-4.60 (m, 2H), 7.48 (d, J=9.1 Hz), 7.88 (dd, J=5.6, 8.1 Hz, 1H), 8.03 (d, J=9.1 Hz, 1H), 8.84, (br d, J=8.1 Hz, 1H), 8.94 (dd, J=1.5, 5.3 Hz, 1H), 9.47 (d, J=1.5 Hz, 1H); mass spectrum m/z 465 ((M+1)+, 17%).

1. waitAfter a few hours the mixture turned to a clear solution
2. stirringThe resulting solution was stirred at room temperature for 24 h
3. concentrationwas concentrated under reduced pressure
4. customThe residue was separated between water (25 mL)
5. washThe resulting organic phase was washed with a saturated sodium bicarbonate solution
6. dry with materialdried (anh. sodium sulfate)
7. concentrationconcentrated under reduced pressure
8. customThe resulting material (0.588 g) purified