Acetic Acid → HCID 136342280, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)(cyclohexyl)methanone (0.35 g, 1.33 mmol; Example #23, Step B), hydroxylamine hydrochloride (0.46 g, 6.7 mmol), N,N-diisopropylethylamine (1.6 mL, 9.32 mmol) and AcOH (0.2 mL, 3.5 mmol) in n-butanol (20 mL) was heated at about 120° C. for about 18 h. Additional hydroxylamine hydrochloride (0.185 g, 2.66 mmol), N,N-diisopropylethylamine (0.70 mL, 4.0 mmol), and AcOH (0.15 mL, 2.7 mmol) were added to the mixture and the reaction was heated at about 120° C. for about 18 h. Additional amounts of hydroxylamine hydrochloride (0.185 g, 2.66 mmol), DIEA (0.70 mL, 4.0 mmol), and AcOH (0.15 mL, 2.7 mmol) were added to the mixture and the reaction was heated at about 130° C. for about 3 days. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The residue was diluted with EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (3×40 mL) and brine (20 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (0-70% EtOAc in heptane gradient as the eluent to provide (5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)(cyclohexyl)methanone oxime as an off white solid (0.193 g, 52%): LC/MS (Table 2, Method a) Rt=2.22 min; m/z: 276 and 278 (M−H)−.

Provenance & Evidence