Ammonia → HCID 49764524, compound

Participants

Reaction Conditions

Reaction Steps

73 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-c]isoquinolin-3-amine are introduced into 5 ml of DCM. After cooling to 0° C. using an ice bath, 0.58 ml of TFA is added and the mixture is stirred at RT for 5 h. The reaction mixture is concentrated under RP and the solid obtained is taken up in 23 ml of water, neutralized with 7.5M aqueous ammonia solution. It is extracted with ethyl acetate, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with DCM and then with a DCM/methanol mixture (90/10 by vol.), to give 5 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-7-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow solid). 1H NMR: 1.61-1.74 (m, 2 H) 2.06-2.16 (m, 2 H) 2.87 (s, 3 H) 2.89-2.95 (m, 2 H) 3.52-3.60 (m, 2 H) 3.75-3.84 (m, 1 H) 5.98 (d, J=8.2 Hz, 1 H) 7.31 (t, J=8.0 Hz, 2 H) 7.65-7.71 (m, 2 H) 7.82-7.88 (broad m, 1 H) 8.15-8.24 (broad m, 1 H) 8.18 (broad d, J=8.3 Hz, 1 H) 8.40 (d, J=8.3 Hz, 1 H) 12.66 (s, 1 H) 13.05 (broad s, 1 H).

Provenance & Evidence