Hydroxyamine hydrochloride → HCID 136391029, compound

Participants

Reaction Steps

A 100 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 211 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde in 8.5 ml of pyridine, 36 mg of hydroxylamine hydrochloride are added, and the mixture is stirred at RT for 64 h. It is concentrated under RP and the solid obtained is taken up in AcOEt, washed with a 1M aqueous solution of potassium phosphate and then with saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated under RP. Purification is carried out by flash chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and AcOEt (75/25 by vol.), to give 184 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde oxime (yellow solid). MS (E/I): m/z=630 (M+); 1H NMR: 0.04 (s, 9H); 0.89 (m, 2H); 1.61 (m, 2H); 2.11 (m, 2H); 2.74 (m, 2H); 2.85 (s, 3H); 3.58 (m, 2H); 3.67 (m, 2H); 4.46 (m, 1H); 5.65 (s, 2H); 6.50 (d, J=8.3 Hz, 1H); 7.33 (broad t, J=8.1 Hz, 2H); 7.65 (m, 1H); 7.72 (broad s, 1H); 8.01 (dd, J=8.4, 17 Hz, 1H); 8.27 (s, 1H); 8.35 (d, J=8.4 Hz, 1H); 11.39 (s, 1H).

Provenance & Evidence