Trifluoroacetic acid → HCID 49764142, compound

Participants

Reaction Conditions

Reaction Steps

A 25 ml round-bottomed flask equipped with a magnetic stirrer is charged with 46 mg of the mixture of methyl 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxylate and methyl 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline-7-carboxylate obtained in step 9 in 5 ml of DCM. After cooling to 0° C. using an ice bath, 0.5 ml of TFA are added and the mixture is stirred at RT for 18 h. It is concentrated under RP and the solid obtained is taken up in 20 ml of water and extracted with three times 20 ml of AcOEt. The organic phase is 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 mixture of DCM/AcOEt (50/50 by vol.), to give 12 mg of methyl 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxylate (yellow solid). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.67 (m, 2 H) 2.11 (m, 2 H) 2.88 (s, 3 H) 2.92 (m, 2 H) 3.56 (m, 2 H) 3.80 (m, 1 H) 3.87 (s, 3 H) 6.16 (d, J=7.7 Hz, 1 H) 7.37 (m, 2 H) 7.71 (m, 1 H) 8.23 (broad s, 1 H) 8.42 (broad d, J=8.5 Hz, 1 H) 8.54 (d, J=8.5 Hz, 1 H) 13.01 (s, 1 H). LC-MS-DAD-ELSD: 516 (+)=(M+H)(+).

Provenance & Evidence