Diisopropylethylamine → 4-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-N-[2-oxo-3-(2,2,2-trifluoroethyl)-1,3-diazinan-1-yl]-2-(trifluoromethyl)benzamide

Participants

Reaction Steps

Into a 25-mL round-bottom flask, was placed 4-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)benzoic acid (100 mg, 0.19 mmol, 1.00 equiv), N,N-dimethylformamide (5 mL), HATU (141 mg, 0.37 mmol, 2.00 equiv), DIEA (96 mg, 0.74 mmol, 4.00 equiv), 1-amino-3-(2,2,2-trifluoroethyl)-1,3-diazinan-2-one (40 mg, 0.20 mmol, 1.10 equiv). The resulting solution was stirred for 3 h at room temperature. The resulting solution was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The mixture was dried over anhydrous sodium sulfate. The residue was purified by preparative TLC (EtOAc/ether=1:2). This resulted in 34.3 mg (26%) of 4-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-N-[2-oxo-3-(2,2,2-trifluoroethyl)-1,3-diazinan-1-yl]-2-(trifluoromethyl)benzamide as a white solid; (ES, m/z): [M+H]+ 719.00, 1H NMR (300 MHz, DMSO): δ 10.72 (s, 1H), 8.37 (s, 1H), 8.23 (s, 2H), 8.16-8.14 (d, J=6 Hz, 1H), 8.08 (s, 1H), 7.74-7.72 (d, 1H), 4.70-4.49 (dd, J=21 Hz, J=45 Hz, 2H), 4.17-4.11 (q, J=9 Hz, 2H), 3.58-3.54 (t, J=6 Hz, 2H), 3.48-3.45 (t, J=5.1 Hz), 2.07-2.05 (m, 2H).

Provenance & Evidence