Potassium Carbonate → HCID 46945564, compound

Participants

Reaction Conditions

Reaction Steps

3-(2,4-Difluorophenyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1H-thieno[2,3-c]pyrazole-5-carboxamide (203.5 mg, 0.523 mmol) and potassium carbonate (331.5 mg, 2.40 mmol) were dissolved in N,N-dimethylformamide (5.20 ml) at 25° C. 2-Iodoethanol (69 μL, 0.885 mmol) was added. The reaction was heated to 50° C. and stirred for 4 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (10 mL), and extracted with ethyl acetate (3×15 mL). The combined organic phases were washed with saturated aqueous ammonium chloride (2×10 mL) and saturated aqueous sodium chloride (1×10 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 40 g column) on a CombiFlash purification system eluting with ethyl acetate-hexanes (0-100%). The title compound (129.6 mg, 0.299 mmol, 57.2% yield) was recovered as a light yellow/white solid. The undesired regioisomer, 3-(2,4-difluorophenyl)-2-(2-hydroxyethyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-2H-indazole-6-carboxamide (33.1 mg, 0.076 mmol, 14.61% yield), was recovered as a light yellow/white solid. Title compound: HRMS [M+1] found=434.1091. 1H NMR (400 MHz, CDCl3): δ 7.99-7.89 (m, 1H); 7.61 (d, J=3.7 Hz, 1H); 7.01-6.91 (m, 2H); 6.80 (d, J=7.8 Hz, 1H); 5.60-5.51 (m, 1H); 4.39-4.34 (m, 2H); 4.15 (d, J=5.4 Hz, 2H); 2.90 (s, 1H); 2.40 (s, 3H); 1.70 (d, J=7.1 Hz, 3H). Regioisomer: HRMS [M+1] found 434.1095.

Provenance & Evidence