Sodium hydride → 4-[4-(1-tert-butoxy carbonylamino-1-methylethyl)phenyl]-5-chloro-N-(4-(1-imidazolyl)-phenyl]pyrimidine-2-amine

Beteiligte Stoffe

Reaktionsschritte

Sodium hydride (330 mg, 8.25 mmol) was added to a solution of 4-[4-(1-tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine (1.0 g, 2.62 mmol) and 1-(4-aminophenyl)-1H-imidazole (438 mg, 2.75 mmol) in dry THF (40 ml) under N2 and the mixture heated to reflux for 3 h. The reaction was quenched with H2O (5 ml), diluted with brine (50 ml) and extracted with ethyl acetate (2×150 ml). The ethyl acetate extracts were dried (MgSO4), concentrated in vacuo and the residue purified by column chromatography (silica; 2% ethyl acetate in CH2Cl2) to give 4-[4-(1-tert-butoxy carbonylamino-1-methylethyl)phenyl]-5-chloro-N-[4-(1-imidazolyl)-phenyl]pyrimidine-2-amine as a yellow solid (310 mg) m.p. 218-220°. This intermediate was stirrd at room temperature in trifluoroacetic acid (4 ml) for 3 h before concentrating the reaction in vacuo. The residue was diluted with 2M NaOH (aq) (50 ml) and extracted with CH2Cl2-ethanol (20:1) (3×50 ml), the extracts dried (MgSO4) and concentrated in vacuo. Trituration of the resultant solid with diethylether-ethyl acetate (4:1) gave the title compound as a pale yellow solid (175 mg) m.p. 199-201°. δH (d6DMSO) 10.05 (1H, bs), 8.62 (1H, s),8.15 (1H, s), 7.88 (2H, d, J 7.9 Hz), 7.78 (2H, d, J 8.5 Hz), 7.69 (2H, d, J 8.5 Hz), 7.65 (1H, s), 7.55 (2H, d, J 8.8 Hz), 1.42 (6H, s). MS (ESI) 405 (MH+, 100%).

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