Methyl vinyl ketone → HCID 86722469, compound

Participants

Reaction Conditions

Reaction Steps

Sodium (1.09 g, 47.4 mmol) and EtOH (355 mL) were stirred together until a solution was formed then 1-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6(1H)-one (115, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (16.47 g, 42.6 mmol) was added. The mixture was heated to about 60° C. then but-3-en-2-one (4.14 mL, 50.2 mmol) was added over about 50 min. The mixture was stirred at about 60° C. for about 90 min then it was cooled and concentrated under reduced pressure. The material was partitioned between EtOAc (250 mL) and water (150 mL) then the aqueous layer was extracted with EtOAc (100 mL). The combined organics were washed with brine (30 mL) then dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified on silica gel (330 g) using a gradient from 0-100% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-9-(4-fluorophenyl)-12b-(pyridin-2-ylmethyl)-1,5,6,7,9,12b-hexahydrobenzo[3,4]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-3(2H)-one (116, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (9.28 g, 50%); LC/MS, method 3, Rt=1.61, 2.40 min, MS m/z 439 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.83 (s, 1H), 8.43 (s, 1H), 8.36-8.28 (m, 3H), 7.61-7.57 (m, 1H), 7.44-7.36 (m, 2H), 7.18-7.11 (m, 2H), 5.97 (s, 1H), 3.88 (d, J=13.4 Hz, 1H), 3.67 (d, J=13.5 Hz, 1H), 3.27-3.15 (m, 1H), 2.98-2.93 (m, 1H), 2.87-2.74 (m, 1H), 2.48-2.40 (m, 1H), 2.39-2.27 (m, 1H), 2.23-2.09 (m, 2H), 1.94-1.75 (m, 2H), 1.56-1.49 (m, 1H).

Provenance & Evidence