反应详情

温度

120 °C

To a 50 mL dried round bottom flask containing a degassed solution of 4-phenyl-1-oxa-3-azaspiro[4.4]nonan-2-one (1 eq., 1.73 mmol) and 4-iodo-N-(quinolin-8-yl)benzamide (1.2 eq.) in DMF (15 mL), potassium carbonate (2.5 eq.) and trans (N,N)-dimethyl cyclohexanediamine (0.5 eq.) was added CuI (0.1 eq). The resulting mixture was stirred at 120° C. for 15 hours. Reaction progress was monitored by TLC (TLC eluent: 10% MeOH in DCM). The reaction mixture was cooled and poured into crushed ice (5 g). The solid thus obtained was filtered, washed with water (25 mL) and dissolved in DCM. The DCM solution was then washed with water (100 mL), washed brine (50 mL) and dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using silica gel and DCM as eluting solvent to yield (R+S) 4-(2-oxo-4-phenyl-1-oxa-3-azaspiro[4.4]nonan-3-yl)-N-(quinolin-8-yl)benzamide (90 mg, 11%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.55 (s, 1H), 8.94 (d, J=4 Hz, 1H), 8.65 (d, J=7.2 Hz, 1H), 8.44 (d, J=8.4 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.75-7.63 (m, 5H), 7.39-7.32 (m, 5H), 5.75 (s, 1H), 2.10-2.20 (m, 2H), 1.50-1.78 (s, 4H), 1.30-1.40 (m, 1H), 1.10-1.20 (m, 1H). m/z (ESI) 464.3 (M+H)+.

1. customTo a 50 mL dried round bottom flask
2. customReaction progress
3. temperatureThe reaction mixture was cooled
4. additionpoured
5. customThe solid thus obtained
6. filtrationwas filtered
7. washwashed with water (25 mL)
8. dissolutiondissolved in DCM
9. washThe DCM solution was then washed with water (100 mL)
10. washwashed brine (50 mL)
11. dry with materialdried over anhydrous Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. custompurified by column chromatography
15. washas eluting solvent