Compound 16
4-(5-(7-fluoroquinolin-4-yl)-1-methyl-1H-imidazol-4-yl)-3,5-dimethylisoxazole
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.
A mixture of 3,5-dimethyl-4-(1-methyl-1H-imidazol-4-yl)-1,2-oxazole (27) (105 mg; 595 µmol), 4-chloro-7-fluoroquinoline (90 mg; 496 µmol), KOAc (146 mg; 1.49 mmol) and Pd(OAc)2 (27.8 mg; 124 µmol) in DMA (2 ml) under argon atmosphere was stirred at 120 °C for 1 h. The mixture was filtered through celite and concentrated in vacuum. Water was added and the mixture was extracted with DCM. The combined organic phases were dried over MgSO4 and concentrated in vacuum. The product was purified by reversed phase chromatography (21 mg; 13%). 1H NMR (500 MHz, DMSO-d6) δ 9.01 (d, J=4.41 Hz, 1H), 8.07 (s, 1H), 7.84 (dd, J=2.68, 10.25 Hz, 1H), 7.52-7.62 (m, 2H), 7.49 (dt, J=2.52, 8.83 Hz, 1H), 3.52 (s, 3H), 1.94 (s, 3H), 1.75 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ ppm 165.9 (s) 162.8 (d, J=248.9 Hz) 159.3 (s) 152.1 (s) 149.6 (d, J=12.7 Hz) 141.0 (s) 136.3 (s) 130.9 (s) 128.6 (br d, J=10.0 Hz) 126.3 (s) 123.7 (s) 123.4 (br d, J=1.8 Hz) 118.1 (br d, J=25.4 Hz) 113.5 (d, J=20.0 Hz) 110.6 (s) 32.8 (s) 11.5 (s) 10.8 (s); HRMS (m/z): [M+H]+ calculated for C18H16FN4O, 323.13027; found, 323.12923; HPLC-MS Rt = 1.03 min.
