Trifluoroacetic acid → HCID 49764141, compound

Participants

Reaction Conditions

Reaction Steps

A 30 ml round-bottomed flask equipped with a septum having a top-mounted argon intake is charged with 47 mg of 5-(2,6-difluorophenyl)-3-([1-(methylsulphonyl)piperidin-4-yl]amino}-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-ethynyl-2H-pyrazolo[4,3-c]isoquinoline in 4 ml of DCM. After cooling to 0° C. using an ice bath, 0.47 ml of TFA is added and the mixture is stirred at RT for 3 h. It is concentrated under RP and the solid obtained is taken up in 25 ml of water and 0.75 ml of 0.75M aqueous ammonia solution. It is extracted with AcOEt, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a mixture of DCM and methanol (92.5/7.5 by vol.). This gives 6 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-7-ethynyl-2H-pyrazolo[4,3-c]isoquinoline (yellow solid). MS (E/1); m/z=481 (M+); 1H NMR: 1.66 (m, 2 H) 2.11 (m, 2 H) 2.87 (s, 3 H) 2.91 (m, 2 H) 3.56 (m, 2 H) 3.79 (m, 1 H) 4.37 (s, 1 H) 6.10 (d, J=8.3 Hz, 1 H) 7.34 (t, J=7.9 Hz, 2 H) 7.65 (broad s, 1 H) 7.69 (m, 1 H) 7.97 (broad d, J=8.3 Hz, 1 H) 8.42 (d, J=8.3 Hz, 1 H) 12.88 (broad s, 1 H).

Provenance & Evidence