Hydrochloric Acid → HCID 57837464, compound

Participants

Reaction Steps

To 2-isopropyl-pyrazolo[1,5-a]pyridine (6.80 g, 42.50 mmol) in n-propionic anhydride (15 mL, 97%) at 140° C. was added concentrated H2SO4 (0.5 ml). The mixture was maintained at 140° C. overnight, cooled to room temperature basified with NaOH (aqueous 50%) until pH>11. The aqueous layer was extracted with chloroform (3×100 mL), dried (Na2SO4), filtered and concentrated. The crude product was purified by flash column chromatography (100% hexane, 9:1 hexane:ethyl acetate) to afford 1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)propan-1-one (4.81 g, 22.27 mmol, 53%) as a yellow oil. 1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)propan-1-one (0.500 g, 2.3 mmol), paraformaldehyde (0.069 g, 2.3 mmol), and benzylamine hydrochloride (0.329 g, 2.3 mmol) were added to a 5-mL round bottom flask. To this ethanolic hydrochloride (1 mL, 1.25% concentrated HCl in ethanol) was added and the mixture was heated to reflux for 16 hours. The mixture was then cooled and diluted with Et2O (5 mL) and 1M NaOH (aq) (10 mL). The aqueous layer was then extracted with Et2O (4×5 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated to afford a dark brown oil. This oil was subjected to flash column chromatography (10% gradient of EtOAc/hexane ranging from 0 to 90%) which afforded 0.073 g (9.5% yield) of 3-(benzylamino)-1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one as a pale yellow oil.

Provenance & Evidence