Iodine → HCID 90200445, compound

Participants

Reaction Steps

Silver(I) nitrate (7.67 g, 45.1 mmol) was added to a solution of 2-(9-bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5 (1H)-ylidene)acetonitrile (100, R1=4-Fluorophenyl) (6.67 g, 17.4 mmol) and 1,4-dioxane (60.0 mL). MeOH (150 mL) was added. The mixture was warmed to reflux. A solution of iodine (5.74 g, 22.6 mmol) and MeOH (22.6 mL) was added over about 20 min. After about 16 h, the mixture was allowed to cool to rt. The volatiles were removed under reduced pressure. The residue was slurried in DCM (200 mL) then filtered rinsing with 10% EtOAc/DCM (6×50 mL). The volatiles were removed under reduced pressure. The residue was purified on silica gel (220 g) using a gradient of 0-50% EtOAc in DCM. The fractions containing the product and intermediate were combined and concentrated under reduced pressure. The material was dissolved in 1,4-dioxane (30 mL). Silver(I) nitrate (2.95 g, 17.4 mmol) was added. MeOH (75 mL) was added and the mixture was warmed to reflux for about 14 h. The mixture was allowed to cool to rt then the volatiles were removed under reduced pressure. The residue was slurried in DCM (100 mL) then filtered rinsing with 10% EtOAc/DCM (4×25 mL). The organics were concentrated under reduced pressure. The residue was dissolved in DCM (100 mL) then washed with water (2×100 mL). The aqueous layers were extracted with DCM (25 mL) then dried over Na2SO4, filtered and concentrated under reduced pressure to afford 10-bromo-1-(4-fluorophenyl)-6,6-dimethoxy-5,6,7,8-tetrahydro-1H-oxepino[3,2-f]indazole-5-carbonitrile acetonitrile (101, R1=4-Fluorophenyl) (5.75 g, 74% yield) as an orange solid. LC/MS, method 3, Rt=2.45 min, MS m/z 446 and 448 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.40 (s, 1H), 8.06 (s, 1H), 7.64-7.55 (m, 2H), 7.42-7.31 (m, 2H), 5.04 (d, J=1.8 Hz, 1H), 4.51-4.38 (m, 1H), 3.70-3.58 (m, 1H), 3.29 (s, 3H), 3.10 (s, 3H), 2.53-2.40 (m, 1H), 2.30-2.21 (m, 1H).

Provenance & Evidence