1-Methylimidazole → HCID 86687750, compound

Participants

Reaction Steps

A solution of 4-(4-(difluoromethyl)-5-fluoro-2-methoxyphenyl)quinazoline-7-sulfonyl chloride (0.300 g, 0.745 mmol) and N-(4-methoxybenzyl)thiazol-4-amine (Intermediate PPPPP; 0.492 g, 2.234 mmol) in 6 mL MeCN was placed under argon and was treated with 1-methylimidazole (0.073 ml, 0.745 mmol). After stirring for 3 hours at room temperature, LC/MS showed mostly product, so the reaction mixture was concentrated. The crude residue was dissolved in TFA (2.295 ml, 29.8 mmol) and was heated to 100° C. for 2 hours. LC/MS showed mostly product, so the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18 30μ, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 4-(4-(difluoromethyl)-5-fluoro-2-methoxyphenyl)-N-(thiazol-4-yl)quinazoline-7-sulfonamide (0.141 g, 0.302 mmol, 40.6% yield). 1H NMR (MeCN-d3) δ: 9.43 (s, 1H), 8.61 (s, 1H), 8.51 (s, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.79-7.86 (m, 1H), 7.37 (d, J=5.4 Hz, 1H), 7.32 (d, J=9.9 Hz, 1H), 6.92-7.25 (m, 2H), 3.71 (s, 3H). (M+H)+=467.0.

Provenance & Evidence