Water → HCID 46202392, compound

Participants

Reaction Steps

To a solution of 6-(2,4-difluorophenyl)-3,4-dihydroquinolin-2(1H)-one (180 mg, 0.69 mmol) (PT-012, made as in Example 1B, above) and 2-((2-methoxyphenoxy)methyl)oxirane (162 mg, 0.90 mmol) in anhydrous N,N-dimethylformamide (2 ml) was added caesium carbonate (326 mg, 1.00 mmol) in a 5 ml Personal Chemistry microwave reaction vial. The reaction vial was sealed, and subjected to microwave irradiation at 180° C. for 40 minutes. The reaction was cooled, poured into water (10 mL), extracted with ethyl acetate (2×30 mL), and the combined organic phases washed with water (30 mL), 2N sodium carbonate (30 mL), brine (40 mL), dried over sodium sulfate, and the solvent removed under reduced pressure. The residue was subjected to reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford 6-(2,4-difluorophenyl)-1-(2-hydroxy-3-(2-methoxyphenoxy)propyl)-3,4-dihydroquinolin-2(1H)-one (148 mg, 0.34 mmol, 49%) (compound No. 88)). LCMS mz 440.0 (M+H), 462.0 (M+Na), anal HPLC >95% in purity. 1H NMR (400 MHz; CDCl3) δ 7.46 (d, J=8.6 Hz, 1H); 7.36 (m, 2H); 7.31 (bs, 1H); 6.88-7.03 (m, 6H); 4.36 (m, H); 4.27 (s, 1H), 4.26 (d, J=2.3 Hz, 1H); 4.15 (dd, J=9.8 and 5.5 Hz, 1H); 4.00-4.10 (m, 2H); 3.88 (s, 3H), 2.99 (m, 2H); 2.76 (m, 2H).

Provenance & Evidence