Compound 9
3,5-dimethyl-4-(1-methyl-5-(pyridin-4-yl)-1H-imidazol-4-yl)isoxazole
From: Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3
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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
To a mixture of 22 (300 mg; 1.26 mmol), 3,5-dimethylisoxazole-4-boronic acid pinacol ester (337 mg; 1.51 mmol) and K3PO4 (0.8 g; 3.78 mmol) in 1,4-dioxane (0.8 ml) and water (0.20 ml) under argon atmosphere was added [1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (82 mg; 0.13 mmol). The reaction mixture was stirred and heated to 120 °C for 16 h. The mixture was filtered through celite and washed with ethyl acetate. The crude mixture was purified by reversed phase chromatography to give 4-[4-(3,5-dimethyl-1,2-oxazol-4-yl)-1-methyl-1H-imidazol-5-yl]pyridine (9) (45 mg; 0.18 mmol; 14%). 1H NMR (500 MHz, DMSO-d6) δ 8.62 (d, J=6.15 Hz, 2H), 7.94 (s, 1H), 7.31 (d, J=6.15 Hz, 2H), 3.70 (s, 3H), 1.95 (s, 3H), 1.92 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 166.0, 159.5, 150.7, 140.9, 137.8, 130.0, 128.4, 124.0, 110.6, 33.1, 11.6, 10.8; HRMS (m/z): [M+H]+ calculated for C14H15N4O, 255.12404; found, 255.12315; HPLC-MS Rt = 0.88 min.
