Ammonia → HCID 49764011, compound

Participants

Reaction Conditions

Reaction Steps

A 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 46 mg of [5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinolin-7-yl]methanol in 4 ml of DCM. After cooling to 0° C. using an ice bath, 0.45 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 25 ml of water and 0.75 ml of a 0.75M aqueous ammonia solution. It is extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. Chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (92.5/7.5 by vol.), gives 13 mg of [5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinolin-7-yl]methanol (yellow solid). MS (E/I): m/z=487 (M+); 1H NMR: 1.67 (m, 2H); 2.11 (m, 2H); 2.87 (s, 3H); 2.90 (m, 2H); 3.56 (m, 2H); 3.79 (m, 1H); 4.63 (d,. J=57 Hz, 2H); 5.34 (t, J=5.7 Hz, 1H); 5.98 (d, J=7.8 Hz, 1H); 7.31 (m, 2H); 7.59 (broad s, 1H); 7.66 (m, 1H); 7.83 (broad d, J=8.3 Hz, 1H); 8.35 (d, J=8.3, 1H); 12.68 (s, 1H).

Provenance & Evidence