Sodium hydride → HCID 86722448, compound

Participants

Reaction Steps

Diethyl (cyanomethyl)phosphonate (11.2 mL, 69.2 mmol) was added dropwise to a slurry of sodium hydride (60 wt % in oil, 2.76 g, 68.9 mmol) in DME (120 mL) under a nitrogen atmosphere at about 0° C. over about 15 min. After completion of addition, the ice bath was removed. After about 30 min, the solution was added to a slurry of 9-bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5 (1H)-one (99, R1=4-Fluorophenyl) (12.5 g, 34.5 mmol) and DME (60 mL) rinsing with DME (60 mL). After about 43 h, the volatiles were removed under under reduced pressure and the residue was dissolved with EtOAc (300 mL) and sat. aq. NH4Cl solution (300 mL). The layers were separated. The organic layer was washed with sat. aq. NaCl (200 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was slurried in DCM (20 mL). The solid was collected by filtration rinsing with DCM (10 mL) then dried under reduced pressure to afford 2-(9-Bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5(1H)-ylidene)acetonitrile (100, R1=4-Fluorophenyl) (2.41 g, 18% yield) as an ivory solid. The mother liquor was purified on silica gel (220 g) using a gradient of 0-2% EtOAc in DCM. The fractions containing the product were combined and concentrated under reduced pressure to afford 2-(9-Bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5(1H)-ylidene)acetonitrile (100, R1=4-Fluorophenyl) (4.92 g, 37% yield) as an ivory solid. LC/MS, method 3, Rt=2.42 min, MS m/z 384 and 386 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.69 (s, 0.33H), 8.50 (s, 0.33H), 8.46 (s, 0.67H), 8.39 (s, 0.67H), 7.60-7.51 (m, 2H), 7.42-7.30 (m, 2H), 6.50-6.46 (m, 0.67H), 5.84-5.81 (m, 0.33H), 4.48-4.42 (m, 0.67H), 4.42-4.36 (m, 1.33H), 3.06-2.98 (m, 1.33H), 2.88-2.82 (m, 0.67H).

Provenance & Evidence