Triethylamine → N-[6-(2-isopropyl-2H-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide

Participants

Reaction Steps

To a solution of 2-amino-4-trifluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (510 mg, 1.56 mmol) in DCM (20 mL) were added Et3N (0.88 mL, 4 equiv) and then (CCl3O)2CO (377 mg, 0.8 equiv). The resulting mixture was stirred at r.t. for 3 h. The solvent was removed in vacuo and the crude intermediate was solubilized in THF. CH3SO2NHNH2(116 mg, 1.0 equiv) was added and the mixture was stirred at r.t. for 1 h. Then, aq NaOH (1N, 1.56 mL) was added and the mixture was stirred for 30 min. The solvent was removed in vacuo and water was added. The pH was adjusted to pH 3-4 by addition of 1N aq HCl. The aqueous phase was extracted with AcOEt twice. The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo to afford a crude solid. The crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (25:75 to 100:0)) to furnish a white solid (285 mg, 42%). (ES-MS: m/z 432.4 [M+H]+, rt 4.61 min) 1H-NMR (DMSO-d6, 400 MHz) 12.05 (bs, 1H); 10.4 (bs, 1H); 7.88 (s, 1H); 7.66 (s, 1H); 7.55 (s, 1H); 6.27 (s, 1H); 4.08 (m, 1H); 3.16 (s, 1H); 1.31 (bd, 6H).

Provenance & Evidence