Acetic Acid → HCID 86722474, compound

Participants

Reaction Conditions

Reaction Steps

A flask was charged with 3-methoxy-6,7-dihydro-5H-cyclohepta[c]pyridin-8(9H)-one (126) (23.0 g, 120 mmol), THF (1000 mL) and picolinaldehyde (32.2 g, 301 mmol). The mixture was cooled to an internal temperature of about −70° C. then lithium bis(trimethylsilyl)amide [1 M solution] (126 mL, 126 mmol) was added over about 30 min keeping the internal temperature below about −65° C. The mixture was allowed to warm to about −10° C. in the cold bath. Acetic acid (13.8 mL, 241 mmol) then water (150 mL) were added. The mixture was concentrated under reduced pressure then partitioned between water (250 mL) and EtOAc (250 mL). The aqueous layer was extracted with EtOAc (150 mL). The combined organic solutions were with brine (100 mL) then dried over MgSO4 then filtered The filtrate was concentrated under reduced pressure then the material was purified on silica gel (330 g) using a gradient from 0-75% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield (E)-3-methoxy-9-(pyridin-2-ylmethylene)-6,7-dihydro-5H-cyclohepta[c]pyridin-8(9H)-one (127, R5=Pyridin-2-yl) (36.15 g, 107%) 1H NMR showed material to contain picolinaldehyde and EtOAc. The material was used in the next step without further purification; LC/MS, method 3, Rt=1.90 min, MS m/z 281 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.54-8.52 (m, 1H), 7.73 (s, 1H), 7.68-7.65 (m, 1H), 7.65 (s, 1H), 7.29-7.25 (m, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.84 (s, 1H), 3.83 (s, 3H), 2.78 (t, J=7.2 Hz, 2H), 2.40 (t, J=7.1 Hz, 2H), 2.05-1.94 (m, 2H).

Provenance & Evidence