Coumarin derivative

Preparation of 2-chloro-N-(7-hydroxy-2-oxo-2H-1-benzopyran-3-yl)benzamide (Compound 2)

(1) Preparation of 3-amino-7-hydroxy-2H-1-benzopyran-2-one.

A mixture of N-(7-hydroxy-2-oxo-2H-1-benzopyran-3-yl)benzamide (230 mg, 0.82 mmol), 1-propanol (6 ml) and concentrated hydrochloric acid (2 ml) was refluxed for 3 hours. Then, hydrochloric acid (2 ml) was added and the mixture was refluxed for further 7 hours. After cooling, the reaction mixture was poured into saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The ethyl acetate layer was washed successively with water and saturated brine, and after the layer was dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (eluent: dichloromethane / ethyl acetate=2 / 1) to give the title compound as a yellow solid (127 mg, 87.7%).

1H-NMR(DMSO-d6, δ): 5.23(2H, s), 6.65-6.70(3H, m), 7.23(1H, d, J=8.4 Hz), 9.81(1H,

Preparation of 3-chloro-N-(7-hydroxy-2-oxo-2H-1-benzopyran-3-yl)benzamide (Compound 3)

Yield: 38.8%

1H-NMR(CDCl3+DMSO-d6, δ): [2.58(a signal of DMSO)], 6.78(1H, d, J=2.4 Hz), 6.84(1H, dd, J=8.7, 2.4 Hz), 7.41(1H, d, J=8.4 Hz), 7.50(1H, t, J=7.5 Hz), 7.57(1H, ddd, J=7.8, 1.8, 1.5 Hz), [7.85(a signal of CHCl3)], 7.86(1H, dt, J=7.5, 1.5 Hz), 7.95-7.96(1H, m), 8.61(1H, s), 9.23(1H, s), 10.12(1H, s).

Preparation of 3-bromo-N-(7-hydroxy-2-oxo-2H-1-benzopyran-3-yl)benzamide (Compound 4)

Yield: 67.9%

1H-NMR(CDCl3+DMSO-d6, δ): [2.59(a signal of DMSO)], 6.86-6.89(2H, m), [7.37(a signal of CHCl3)], 7.39(1H, d, J=6.0 Hz), 7.42(1H, d, J=8.1 Hz), 7.71(1H, ddd, J=7.8, 1.8, 1.2 Hz), 7.83(1H, ddd, J=7.8, 1.8, 1.2 Hz), 8.06(1H, t, J=1.8 Hz), 8.73(1H, s), 8.76(1H, s), 9.79(1H, s).