Trifluoroacetic acid → 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide

Participants

Reaction Steps

A 50 ml round-bottom flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 300 mg of 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide in 8 ml of DCM. 3 ml of TFA are added and the mixture is stirred at RT for 2 h. It is concentrated under RP and the solid obtained is taken up in 30 ml of water and 2 ml of 0.75M aqueous ammonia solution. The product is extracted with AcOEt, dried over MgSO4, filtered and concentrated under RP. Chromatography on silica gel (15-40 μm), eluting with AcOEt, gives 30 mg of 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide (pale yellow solid). MS (E/I): m/z=554 (M+); 1H NMR: 1.69 (m, 2H); 2.17 (m, 2H); 3.38 (m, 2H); 3.83 (m, 2H); 3.93 (m, 1H); 6.24 (m, 1H); 7.33 (t, J=8.0 Hz, 2H); 7.58 (broad s, 1H); 7.69 (m, 1H); 8.17 (broad s, 1H); 8.23 (broad s, 1H); 8.36 (broad d, J=8.5 Hz, 1H); 8.44 (d, J=8.5 Hz, 1H); 12.9 (broad s, 1H).

Provenance & Evidence