2,6-Lutidine → HCID 67191038, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-pyran-4-yl)-propionic acid (prepared as in PCT WO 2003/095438 A1, Example 20, 86 mg, 0.25 mmol) was dissolved in methylene chloride (3 mL) and N,N-dimethylfomamide (three drops) at 25° C. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 0.14 mL, 0.26 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 (3 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, 39 mg, 0.25 mmol), 2,6-lutidine (58 μL, 0.49 mmol), and methylene chloride (2 mL) which was cooled to 0° C. The reaction was allowed to warm to 25° C. and stirred for a period of 2 h. After this time, the reaction quenched with a small amount of methanol and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 50% ethyl acetate/hexanes) to afford 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-3-(tetrahydro-pyran-4-yl)-propionamide (69 mg, 57%) as a white foam.

Provenance & Evidence