Acetone → HCID 46946170, compound

Participants

Reaction Steps

N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(4-methylphenyl)-3-(prop-1-en-2-yl)-1H-indazole-6-carboxamide (40.6 mg, 0.101 mmol) was dissolved in acetone (919 μl)/water (92 μl). N-methylmorpholine oxide (15.2 mg, 0.130 mmol) was added. Osmium tetroxide (2.5% in n-butanol, 32 μl, 2.55 mmol) was added. The reaction mixture was stirred at room temperature for 2.5 h. The reaction was stopped, quenched by addition of saturated aqueous sodium sulfite (5 mL), and extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×5 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The residue was purified by preparative HPLC (reverse phase, C-18), eluting with acetonitrile/water+0.1% trifluoroacetic acid. The product fraction was diluted with ethyl acetate (15 mL), washed with saturated aqueous sodium bicarbonate (2×15 mL) and saturated aqueous sodium chloride (1×10 mL), dried (sodium sulfate), and the solvent evaporated under reduced pressure to give the title compound (1:1 mixture of diastereomers) (32.9 mg, 0.076 mmol, 74.7% yield) as a white solid. HRMS: [M+1]=436.2001. 1H NMR (500 MHz, CDCl3): δ 8.15 (s, 1H); 8.00 (dd, J=8.5, 4.7 Hz, 1H); 7.53-7.46 (m, 3H); 7.30 (d, J=7.9 Hz, 2H); 7.13 (d, J=8.0 Hz, 1H); 5.58 (t, J=7.3 Hz, 1H); 4.22 (dd, J=11.3, 3.3 Hz, 1H); 3.78 (d, J=11.4 Hz, 1H); 2.42 (s, 3H); 2.45-2.28 (m, 3H); 1.71-1.65 (m, 6H).

Provenance & Evidence