2,6-Lutidine → HCID 67188972, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (R)-2-(3-chloro-4-cyclopentanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (0.15 mmol) is dissolved in methylene chloride (5 mL) and N,N-dimethylformamide (one drop) and cooled to 0° C. To this solution is added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 1.2 equiv.) and it is then allowed to warm to 25° C. and stirred 1 h at 25° C. After this time, the reaction is concentrated in vacuo to ⅓ of the original volume. In a separate flask, a solution of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared as in Example 80, 1.5 equiv.), 2,6-lutidine (2.0 equiv.) and methylene chloride (5 mL) is cooled to 0° C. in an ice bath. To this solution is added the solution of the prepared acid chloride, diluted with another portion of methylene chloride (2 mL) dropwise. After the addition is complete the reaction is then allowed to warm to 25° C. and stirred for 16 hours. After this time the reaction mixture is diluted with methylene chloride (10 mL) transferred to a separatory funnel and washed with a saturated aqueous sodium bicarbonate solution (10 mL) and then a 1 N aqueous hydrochloric acid solution (10 mL) and then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (silica gel column) will afford (R)-2-(3-chloro-4-cyclopentanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide.

Provenance & Evidence