反应详情

8-(1-aminoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (232 mg, 0.67 mmol, [α]D20°: +35° in acetonitrile), 3,4,5-trifluorophenylboronic acid (236 mg, 1.34 mmol), diacetoxycopper hydrate (148 mg, 0.74 mmol) and molecular sieves 4 A (1 g) were weighed out in a flask. Dichloroethane (4 mL) then pyridine (0.109 mL, 1.34 mmol) were added and the resulting mixture was stirred at RT for 2 days under an oxygen atmosphere. The mixture was diluted with DCM, filtered through a pad of celite, the filtrate was washed with a 0.5N NaOH aq. sol. and the aqueous phase extracted with DCM. The combined organics were dried over magnesium sulphate and concentrated down. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in ethyl acetate/DCM (1:1). The solvent was evaporated to dryness to afford N,N-dimethyl-2-morpholino-4-oxo-8-(1-(3,4,5-trifluorophenylamino)ethyl)-4H-chromene-6-carboxamide single enantiomer (100 mg, 31%) as a white foam. Mass Spectrum: M+H+ 476. [α]D20°: −108° in MeCN. NMR Spectrum (CDCl3): 1.56 (d, 3H), 2.91 (s, 3H), 3.09 (s, 3H), 3.47-3.56 (m, 4H), 3.82-3.90 (m, 4H), 4.35 (d, 1H), 4.79-4.88 (m, 1H), 5.56 (s, 1H), 6.03 (dd, 2H), 7.70 (d, 1H), 8.12 (d, 1H).

1. filtrationfiltered through a pad of celite
2. washthe filtrate was washed with a 0.5N NaOH aq. sol.
3. extractionthe aqueous phase extracted with DCM
4. dry with materialThe combined organics were dried over magnesium sulphate
5. concentrationconcentrated down
6. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in ethyl acetate/DCM (1:1)
7. customThe solvent was evaporated to dryness