反应详情

温度

55 °C

To a solution of 100 mg (0.22 mmol) of acetic acid 1-(3-methanesulfonylamino-2,4-dioxo-7 -trifluoromethyl-1,2,3,4-tetrahydro-quinazolin-6-yl)-1H-pyrrol-3-ylmethyl ester in 0.5 ml of methanol are added 36.4 mg (0.26 mmol) of potassium carbonate and the reaction mixture is stirred at 55° C. for 8 hours. The mixture is cooled to room temperature and stirred for another 12 hours. Subsequently a pH 7 phosphate buffer solution for neutralization is added to the reaction mixture and the solvents are evaporated carefully (risk of degradation). The crude residue is purified by preparative thin layer chromatography (dichloromethane/methanol, 8/2) to yield N-[6-(3-hydroxymethyl-pyrrol-1-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide: 1H-NMR; DMSO-d6 (400 MHz, ppm): 7.82 (s, 1H , aromatic); 7.64 (s, 1H , aromatic); 6.86 (m, 1H, N-CH═CH in pyrrol); 6.84 (s, 1H, N-CH═C(CH2) in pyrrol); 6.21 (m, 1H, CH═CH-C(CH2)-N in pyrrol); 4.37 (d, 2H, CH2-OH); 3.16 (s, 3H, S02-CH3); LC-MS: 417 [M-H]-; Agilent LC/MSD 1100 Series, LC-MS method: Column: SunFireC18, 4.6*50 mm, 3.5 μm; negative MS; water/acetonitril 95:5 to 5:95 in 5 min, flow: 1.5 ml/min.

1. temperatureThe mixture is cooled to room temperature
2. stirringstirred for another 12 hours
3. customthe solvents are evaporated carefully (risk of degradation)
4. customThe crude residue is purified by preparative thin layer chromatography (dichloromethane/methanol, 8/2)