2-Pyridinecarboxaldehyde → HCID 86722338, compound

Participants

Reaction Conditions

Reaction Steps

A 3 neck round bottom flask with stir bar, nitrogen line and thermometer was charged with 1-(4-fluorophenyl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6 (1H)-one (6, R1=4-Fluorophenyl) (0.500 g, 1.699 mmol) and THF (15 mL). The solution was cooled to about −60° C. then LiHMDS (1M in THF, 2.0 mL, 2.0 mmol) was added. After complete addition the mixture was removed from the cold bath and allowed to warm to about 0° C. The mixture was cooled to about −65° C. then picolinaldehyde (0.546 g, 5.10 mmol) was added and the temperature of the mixture was raised to about −5° C. After about 15 min the reaction was quenched with AcOH (1 mL) and stirred for about 15 min. The mixture was transferred to a separatory funnel with the aid of EtOAc (25 mL) and sat. aq. NaHCO3 (25 mL). The layers were separated then the aq. layer was extracted with EtOAc (25 mL). The combined organic layers were washed with brine (15 mL) then dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (12 g) using a gradient of 0-40% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield (E)-1-(4-fluorophenyl)-5-(pyridin-2-ylmethylene)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (0.519 g, 80%); LC/MS, method 3, Rt=2.54 min, MS m/z 384 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.56-8.54 (m, 1H), 8.23 (d, J=0.8 Hz, 1H), 7.89-7.83 (m, 3H), 7.69 (s, 1H), 7.59-7.51 (m, 1H), 7.53 (s, 1H), 7.51-7.41 (m, 2H), 7.22-7.20 (m, 1H), 6.97 (d, J=8.0 Hz, 1H), 2.99 (t, J=7.0 Hz, 2H), 2.38 (t, J=6.9 Hz, 2H), 2.09-1.95 (m, 2H).

Provenance & Evidence