Methanol → HCID 66770599, compound

Participants

Reaction Conditions

Reaction Steps

239 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, prepared in step 4 of example 7, are introduced into 4 ml of methanol and 4 ml of DMF, and 208 μL of trimethylsilyl azide and 15 mg of copper(I) iodide are added. After 2 h of heating at 100° C., 104 μl of trimethylsilyl azide and 7 mg of copper(I) iodide are added and heating at 100° C. is continued for 2 h. After cooling, the mixture is poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (40-63 μm), eluting with a DCM/methanol mixture (95/05 by vol.), to give 121 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-7-(2H-1,2,3-triazol-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow foam). 1H NMR: −0.04 (s, 9 H) 0.90 (m, 2 H) 1.61 (m, 2 H) 2.12 (m, 2 H) 275 (m, 2 H) 2.85 (s, 3 H) 3.57 (m, 2 H) 3.68 (m, 2 H) 4.47 (m, 1 H) 5.66 (s, 2 H) 6.49 (d, J=8.4 Hz, 1 H) 7.36 (t, J=8.0 Hz, 2 H) 7.67 (m, 1 H) 8.01 (broad s, 1 H) 8.25 (broad d, J=8.5 Hz, 1 H) 8.41 (d, J=8.5 Hz, 1 H) 8.43 (partially masked broad m, 1 H) 15.28 (broad m, 1 H).

Provenance & Evidence