Ammonium Acetate → HCID 178455690, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 113 mg (0.50 mmol) (2E)-2-[(3-methyl-1H-indazol-5-yl)methylidene]-3-oxobutanenitrile (Example 2A) and 432 mg (0.50 mmol based on 17% purity) 4,4-difluoro-3-oxohexanenitrile (Example 13A) in 2-propanol (334 μl) and acetic acid (170 μl) was treated with 116 mg (1.5 mmol) ammonium acetate and stirred for 20 min at 90° C. under microwave conditions. After cooling, the mixture was concentrated under reduced pressure, and the residue was suspended in p-xylene (1.5 ml). Small amounts of p-toluenesulfonic acid and powdered 4 Å molecular sieve were added, and the mixture was stirred at reflux temperature for 48 h. Upon cooling, the mixture was diluted with acetonitrile, filtered and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 9:1 v/v) followed by preparative thin layer silica gel chromatography (toluene/ethanol 5:1 v/v) to yield 7.2 mg (4% of th.) of the racemic title compound as a pale yellow solid.

Provenance & Evidence