HCID 66773299, compound → HCID 178509480, compound

Participants

Reaction Steps

707 mg of 3-bromo-5-(2,6-difluorophenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile are introduced into 17 ml of 1,4-dioxane. After argon has been bubbled through the mixture for 10 min, 846 mg of 4-aminopiperidine-1-sulphonamide, 2.15 g of caesium carbonate, 95 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene and 30 mg of palladium(II) acetate are added. The mixture is heated at reflux for 20 h. After cooling, the mixture is poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (40-63 μm), eluting with a DCM/EtOH/NH3 (7N solution in MeOH) mixture (90/10/1 by vol.), to give 407 mg of 5-(2,6-difluorophenyl)-3-(piperidin-4-ylamino)-2-[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile (yellow oil). 1H NMR: −0.05 (broad s, 9 H) 0.88 (t, J=7.9 Hz, 2 H) 1.39 (m, 2 H) 1.93 (m, 2 H) 2.08 (broad m, 1 H) 2.39 (m, 2 H) 2.93 (m, 2 H) 3.71 (t, J=7.9 Hz, 2 H) 4.42 (m, 1H) 5.66 (s, 2 H) 6.58 (d, J=8.1 Hz, 1 H) 7.33 (t, J=7.9 Hz, 2 H) 7.66 (m, 1 H) 7.95 (broad s, 1 H) 8.12 (broad d, J=8.3 Hz, 1 H) 8.46 (d, J=8.3 Hz, 1 H).

Provenance & Evidence