反应详情

A solution of diethyl N-(4-(((1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl)amino)-2-fluorobenzoyl)-L-glutamate (2.3 g, 4.1 mmol) in ethanol (25 ml) and 0.2 N NaOH (100 ml) was stirred under nitrogen at room temperature for 3 hours. The solution was adjusted to pH 7 with 1 N HCl and reduced in volume under vacuum to remove the ethanol. The product was precipitated by acidifying the solution with 1 N HCl to pH 3 with stirring under nitrogen. The suspension was stirred 15 minutes, filtered under nitrogen, washed with water, pressed with a sheet of latex to remove excess water, and dried under high vacuum to give N-(4-(((1,2-dihydro-3-methyl-1-oxobenzo[f]quina-zolin-9-yl)methyl)amino)-2-fluorobenzoyl)-L-glutamic acid as a white solid (2.1 g). 1H NMR (DMSO-d6,300 MHz) d: 1.82-2.12 (m, 2H, glu CH2), 2.29 (t, J=7 Hz, 2H, glu CH2), 2.43 (s, 3H, C3—CH3), 4.32-4.42 (m, 1H, glu CH), 4.57 (d, J=6 Hz, 2H, C9—CH2), 6.39 (dd, J=15.2 Hz, 1H, Ar), 6.53 (dd, J=9.2 Hz, 1H, Ar), 7.30 (t, J=6 Hz, 1H, ArNH), 7.47 (dd, J=9.9 Hz, 1H Ar), 7.59(d, J=9 Hz, 1H, Ar), 7.61(dd, J=8.2 Hz, 1H, Ar), 7.73 (t, J=7 Hz, 1H, glu NH), 8.01 (d, J=8 Hz, 1H, Ar), 8.22 (d, J=9 Hz, 1H, Ar), 9.85 (s, 1H, Ar), 12.42 (br s, 2H, CO2H's), 12.53 (s, 1H, N2H). Anal. Calculated for C26H23FN4O6. 3/2 H2O.1/3 NaCl: C, 56.49; H, 4.74; N, 10.14; Cl, 2.12; Na, 1.37. Found: C, 56.48; H, 4.64; N, 10.20; Cl, 2.01; Na, 1.30.

1. customto remove the ethanol
2. customThe product was precipitated
3. stirringThe suspension was stirred 15 minutes
4. filtrationfiltered under nitrogen
5. washwashed with water
6. customto remove excess water
7. customdried under high vacuum