HCID 68512093, compound → N-(4-(1-(4-methoxybenzyl)-3-(5-((4-methylpiperazin-1-yl)methyl)furan-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of N-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (35 mg, 0.0503 mmol, prepared according to Example 66, Step C) and a 14:86 mixture of 1-methyl-4-((4-(tributylstannyl)furan-2-yl)methyl)piperazine and 1-((4-bromo-5-(tributylstannyl)furan-2-yl)methyl)-4-methylpiperazine (26.0 mg, 0.0554 mmol, prepared according to Example 66, Step B) in dioxane (0.5 mL) was sparged with N2 for 2 minutes, and then PdCl2(PPh3)2 (2 mg, 0.003 mmol) was added. The reaction was heated at 90° C. for 18 hours in a sealed vessel. After cooling to ambient temperature, the crude reaction mixture was loaded directly on to a preparative TLC plate (0.5 mm thickness, Rf=0.60) eluting with 90:10 CHCl3/MeOH (containing 7N NH3). The product was isolated as an off-white solid (27 mg, 83:17 mixture of N-(4-(1-(4-methoxybenzyl)-3-(3-bromo-5-((4-methylpiperazin-1-yl)methyl)furan-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide and N-(4-(1-(4-methoxybenzyl)-3-(5-((4-methylpiperazin-1-yl)methyl)furan-3-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide). 1H-NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 8.32 (d, J=6 Hz, 1H), 8.18 (s, 1H), 7.71 (m, 1H), 7.42 (m, 4H), 7.21 (m, 2H), 7.06 (t, J=9 Hz, 2H), 6.84 (d, J=9 Hz, 2H), 6.41 (s, 1H), 6.26 (d, J=6 Hz, 1H), 5.70 (s, 2H), 3.76 (s, 3H), 3.54 (m, 2H), 2.25-2.63 (m, 8H), 2.19 (s, 3H), 1.79 (m, 2H), 1.61 (m, 2H). The mixture of products was used directly in the next step.

Provenance & Evidence