Hydrochloric Acid → HCID 178504949, compound

Participants

Reaction Conditions

Reaction Steps

A 10 ml round-bottomed flask is charged with 30 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile, prepared in example 12, 1.3 ml of methanol, 0.8 ml of THF and 62 mg of triethylamine. 44 mg of hydroxylamine as the hydrochloride are added. The mixture is heated at 65° C. for 3 h and then evaporated under RP. The solid obtained is taken up in 10 ml of water and extracted with AcOEt. The organic phase is dried over MgSO4, filtered and concentrated under RP. It is purified by flash chromatography on silica gel (15-40 μm), eluting with DCM and then with a DCM/methanol mixture (80/20 by vol.), to give 9.7 mg of 5-(2,6-difluorophenyl)-N-hydroxy-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboximidamide in the form of a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.67 (m, 2 H) 2.11 (m, 2 H) 2.91 (m, 2 H) 2.87 (s, 3 H) 3.56 (m, 2 H) 3.79 (m, 1 H) 5.95 (broad s, 2 H) 6.03 (d, J=7.9 Hz, 1 H) 7.31 (m, 2 H) 7.66 (m, 1 H) 7.95 (broad s, 1 H) 8.18 (dd, J=8.5, 1,6 Hz, 1H) 8.39 (d, J=8.5 Hz, 1 H) 9.82 (s, 1 H) 12.76 (s, 1H). LC-MS-DAD-ELSD: 516 (+)=(M+H)(+).

Provenance & Evidence