Methyl vinyl ketone → HCID 86722327, compound

Participants

Reaction Conditions

Reaction Steps

A three necked round bottom flask with septum, nitrogen line, thermometer and stir bar was charged with EtOH (50 mL) and sodium (0.348 g, 15.1 mmol). The mixture was stirred until the reaction was complete, then 5-ethyl-1-(4-fluorophenyl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (7, R1=4-Fluorophenyl, R2=Ethyl) (3.25 g, 10.1 mmol) suspended in EtOH (50 mL) was added. The mixture was heated to about 35° C. for about 10 min then methyl vinyl ketone (0.777 g, 11.09 mmol) was added. The mixture was stirred for about 45 min at about 35° C. then heated to about 60° C. for about 1 h. Methyl vinyl ketone (0.27 g, 3.85 mmol) was added and stirring was continued for about 30 min. Methyl vinyl ketone (0.22 g, 3.14 mmol) was added then heating was continued for about 45 min. The mixture was cooled to rt then concentrated under reduced pressure. Water (100 mL) and EtOAc (100 mL) were added then the mixture was acidified to about pH 1 with 6 N aq. HCl. The layers were separated then the aqueous layer was extracted with EtOAc (20 mL). The combined organic solutions were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (120 g) using a gradient of 10-50% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure to yield 12b-Ethyl-9-(4-fluorophenyl)-1,2,6,7,9,12b-hexahydro-5H-9,10-diaza-benzo[3,4]cyclohepta[1,2-f]inden-3-one (8, R1=4-Fluorophenyl, R2=Ethyl) (3.03 g, 80%); LC/MS, method 3, Rt=2.73 min, MS m/z 375 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.32 (s, 1H), 7.89 (s, 1H), 7.85-7.78 (m, 2H), 7.63 (s, 1H), 7.47-7.38 (m, 2H), 5.89 (s, 1H), 3.03-2.95 (m, 1H), 2.88-2.63 (m, 2H), 2.58-2.27 (m, 4H), 2.21-2.00 (m, 2H), 1.93-1.73 (m, 3H), 0.92-0.84 (t, J=7.2 Hz, 3H).

Provenance & Evidence