1-Methylimidazole → 4-[2-Methoxy-4-(trifluoromethyl)phenyl]-N-4-pyrimidinyl-7-quinazolinesulfonamide

Participants

Reaction Conditions

Reaction Steps

A solution of pyrimidin-4-amine (0.029 g, 0.300 mmol) in 3 mL of MeCN was treated with SEM-Cl (0.053 ml, 0.300 mmol), and the reaction mixture was allowed to stir for one hour. 4-(2-methoxy-4-(trifluoromethyl)phenyl)quinazoline-7-sulfonyl chloride (Intermediate DDDD; 0.110 g, 0.273 mmol) was added as a solution in 3 mL of MeCN, followed by 1-methylimidazole (0.054 ml, 0.546 mmol). After stirring at room temperature for an additional hour, the reaction mixture was concentrated and then dissolved in 1 mL of THF. 4N HCl dioxanes (1.024 ml, 4.10 mmol) was added, and the reaction mixture was heated to 110° C. for one hour. The reaction mixture was concentrated and purification of the crude residue by reverse phase column chromatography [C18 50 g, 10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielded 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide. 1H NMR (acetonitrile-d3) δ ppm: 9.44 (s, 1H), 8.63 (s, 1H), 8.44 (s, 1H), 8.18 (br. s., 1H), 8.03 (d, J=8.8 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.58 (d, J=7.4 Hz, 1H), 7.43-7.51 (m, 2H), 7.07 (br. s., 1H), 3.75 (s, 3H). m/z (ESI) 462.0 (M+H)+

Provenance & Evidence