Acetic Acid → HCID 86722465, compound

Participants

Reaction Conditions

Reaction Steps

1-(4-Fluorophenyl)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6 (1H)-one (114, R1=4-Fluorophenyl) (15.0 g, 50.8 mmol) and THF (430 mL) were stirred until a solution formed. The mixture was cooled to about −70° C. then LiHMDS (1M in THF, 53 mL, 53.0 mmol) was added keeping the internal temperature between about −65 and −70° C. After about 45 min picolinaldehyde (16.32 g, 152 mmol) was added. After about 5 min the mixture was allowed to warm to about −10° C. over about 90 min. Acetic acid (5.8 mL, 102 mmol) was added to the mixture then the slurry was concentrated under reduced pressure. The material was partitioned between water (500 mL), sat. aq. NaHCO3 (˜75 mL) and DCM (200 mL). The aqueous layer was extracted with DCM (60 mL) then the combined organics were dried over MgSO4, filtered and concentrated on the rotovap to yield (E)-1-(4-fluorophenyl)-5-(pyridin-2-ylmethylene)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6(1H)-one which was used directly in the next step without further manipulation; LC/MS, method 3, Rt=2.46 min, MS m/z 385 (M+H)+.

Provenance & Evidence