Compound 1
1-(3-(4-((4-methoxy-[1,1'-biphenyl]-3-yl)amino)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)ethanone
From: Overcoming resistance to HER2 inhibitors through state-specific kinase binding
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
Crude 4 was added to a microwave tube containing 54.2 mg of 3-acetylphenyl-boronic acid (0.31 mmol), and 68.5 mg of potassium phosphate (0.31 mmol) in 1.5 mL of dioxane:H2O (3:1) with a stir bar, which was sparged with argon for 5 min. 6.3 mg of XPhos Pd G2 (.0078 mmol) and 7.8 mg of SPhos (.016 mmol) were then added to the microwave tube which was purged with argon and heated to 150°C for 20 min in a microwave. The reaction was cooled, concentrated in vacuo, and the residue was purified by silica gel chromatography (eluent, Hex:EtOAc = 3:1 to 1:3) to give 26.4 mg (62.5% over 2 steps) of 1 as a white powder. MS (ES+) m/z 436.9 (M + H)+1; 1H NMR (DMSO-d6, 400 MHz) δ 1.66 (s, 3H), 3.60 (s, 3H), 7.08 (d, 1H, J=8.6 Hz), 7.33 (m, 2H), 7.47 (t, 2H, J =7.7 Hz), 7.62 (m, 2H), 7,84 (t, 1H, J=7.7 Hz), 7.98 (s, 1H), 8.06 (dt, 1H, J=7.7, 1.3 Hz), 8.21 (dt, 1H, J=7.8, 1.3 Hz), 8.33 (t, 1H, J=1.5 Hz), 8.60 (s, 1H), 9.12 (d, 1H, J=2.2 Hz), 14.04 (s, 1H); 13C NMR (DMSO-d6, 400 MHz) δ 27.29, 56.19, 99.25, 111.45, 118.68, 121.87, 126.84, 127.38, 128.70, 128.86, 129.08, 129.40, 130.35, 133.3, 133.73, 133.97, 137.98, 140.71, 143.5, 148.09, 154.45, 155.99, 156.1, 198.1.
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316894703
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