Tetrahydrofuran → 1-(2-Methylpyridin-4-yl)-5-(pyridin-2-ylmethylene)-5,7,8,9-tetrahydrocyclohepta[f]indazol

Participants

Reaction Conditions

Reaction Steps

A round bottom flask was charged with 1-(2-methylpyridin-4-yl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (6, R1=2-methylpyridin-4-yl) (2.83 g, 9.71 mmol) and THF (43 mL). The solution was cooled to about −77° C. and then lithium bis(trimethylsilyl)amide (1.0 M in THF, 10.0 mL, 10.0 mmol) was added over about 30 min, keeping the internal temperature below about −75° C. After the addition was the mixture was stirred for about 5 min, the cold bath was removed and the mixture was allowed to warm to about 0° C. over about 1 h. The mixture was again cooled to about −75° C. then 2-pyridinecarboxaldehyde (3.2 mL, 34 mmol) was added. The mixture was allowed to warm to about −10° C. over about 1 h, and then water (40 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×40 mL) and then the combined organics were washed with brine (50 mL), dried over Na2SO4 and then concentrated under reduced pressure. The crude material was purified on silica gel (120 g, eluted with 0% to 2.5% MeOH in DCM). Collection and concentration of the appropriate fractions gave 1-(2-methylpyridin-4-yl)-5-(pyridin-2-ylmethylene)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H-one (83, R1=2-methylpyridin-4-yl, R2′=pyridin-2-yl) (3.45 g, 93%) LC/MS, method 3, Rt=1.95 min, MS m/z 381 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.65 (d, J=5.7 Hz, 1H), 8.61-8.53 (m, 1H), 8.11-8.08 (m, 1H), 7.95 (s, 1H), 7.82 (s, 1H), 7.80-7.64 (m, 2H), 7.53 (s, 1H), 7.44-7.35 (m, 1H), 7.14-7.06 (m, 1H), 6.92 (d, J=7.9 Hz, 1H), 3.14-3.06 (m, 2H), 2.78 (s, 3H), 2.56-2.48 (m, 2H), 2.23-2.08 (m, 2H).

Provenance & Evidence