Ethyl Acetate → HCID 178435467, compound

Participants

Reaction Conditions

Reaction Steps

A 250 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 2.22 g of 3-bromo-5-(2,6-difluorophenyl)-7-iodo-1H-pyrazolo[4,3-c]isoquinoline in 11 ml of DMF. After argon has been bubbled through the mixture for 10 min, 1.47 ml of tributylvinylstannane and 481 mg of bis(triphenylphosphene)palladium(II) dichloride are added. The mixture is heated at 100° C. for 1 h and then after cooling is evaporated to dryness under vacuum. This gives an oil which is taken up in 350 ml of AcOEt and 300 ml of 20% aqueous KF solution. The mixture is stirred at RT for 30 min and then the suspension is filtered on a glass frit bearing a bed of Clarcel Flo. The organic phase is extracted with AcOEt and then washed with saturated aqueous NaCl solution, dried over MgSO4 and evaporated to dryness under RP. This gives 3.1 g of a crude product, which is purified by chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (95/5 by vol.), to give 1.44 g of 3-bromo-5-(2,6-difluorophenyl)-7-vinyl-1H-pyrazolo[4,3-c]isoquinoline (light yellow solid). MS (E/I): m/z=386 (M+); 1H NMR: 5.43 (d, J=11.2 Hz, 1H); 6.00 (d, J=17.6 Hz, 1H); 6.92 (dd, J=17.6, 11.2 Hz, 1H); 7.37 (t, J=7.9 Hz, 2H); 7.65 (broad s, 1H); 7.73 (m, 1H); 8.33 (dd, J=8.8, 1.5 Hz, 1H); 8.51 (d, J=8.8 Hz, 1H); 14.59 (broad m, 1H).

Provenance & Evidence