2,6-Lutidine → HCID 67192941, compound

Participants

Reaction Conditions

Reaction Steps

2-(3,4-Dichloro-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid (152 mg, 0.50 mmol) was dissolved in methylene chloride (5 mL) and N,N-dimethylfomamide (three drops) at 25° C. under argon. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 270 μL, 0.53 mmol) which produced gas evolution and it was then stirred at 25° C. for 30 minutes. After this time, the reaction was concentrated in vacuo and the residue was then taken up in methylene chloride (5 mL). This solution was then added dropwise to a flask containing a solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in Example 80, 78 mg, 0.50 mmol), 2,6-lutidine (130 μL, 1.00 mmol), and methylene chloride (5 mL) which was 0° C. The reaction was allowed to warm to 25° C. and stirred for a period of 2 h. After this time, the reaction was quenched with a small amount of methanol and then concentrated in vacuo. It was then dissolved in ethyl acetate (25 mL) and washed with a 1N hydrochloric acid solution (1×10 mL) and a saturated aqueous sodium chloride solution (1×10 mL). The organic layer was then dried over sodium sulfate and concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 100% ethyl acetate) to afford 2-(3,4-dichloro-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (149 mg, 81%) a 1:1 enantiomeric reaction as a white foam.

Provenance & Evidence