Compound 8
4-(1-methyl-4-phenyl-1H-imidazol-5-yl)pyridine
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 solution of 4-pyridylcarboxaldehyde (53 µl; 0.55 mmol) in 1.5 ml THF was treated with methylamine (369 µl of a 2 M solution in THF; 0.74 mmol). The mixture was stirred overnight at rt. Piperazine (41.3 mg; 0.48 mmol) was added followed by 1-phenyl-1-tosyl)methyl isocyanide (100 mg; 0.37 mmol) and the mixture stirred at rt for 48 h. The mixture was diluted with EtOAc, washed with water and sat. NaHCO3, dried over MgSO4, filtered and concentrated. The product was purified by silica gel chromatography (0-15% MeOH/DCM over 15 min). The product was then triturated with Et2O to give a cream solid. 1H NMR (500 MHz, DMSO-d6) δ 8.67 (d, J=5.99 Hz, 2H), 7.87 (s, 1H), 7.41 (d, J=5.99 Hz, 2H), 7.32-7.38 (m, 1H), 7.26 (t, J=7.57 Hz, 2H), 7.19 (d, J=7.25 Hz, 1H), 3.55 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 150.7, 139.8, 138.9, 138.8, 134.8, 128.7, 127.1, 127.1, 126.4, 125.4, 32.6; HRMS (m/z): [M+H]+ calculated for C15H14N3, 236.11822; found, 236.11793; HPLC-MS Rt = 0.88 min.
