Cesium carbonate → 3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-benzimidazol-4-yl]oxy}benzonitrile dihydrochloride

関与物質

反応手順

To a suspension of 3-chloro-5-[(5-chloro-1H-benzimidazol-4-yl)oxy]benzonitrile (101 mg, 0.332 mmol) and tert-butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (104 mg, 0.332 mmol) in DMF (1 mL) was added cesium carbonate (216 mg, 0.664 mmol) and the suspension was stirred at room temperature for 2.25 hours. This mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×12 mL). The combined extracts were washed with water, dried over MgSO4, filtered and evaporated in vacuo. This residue was purified on silica gel (40 g) column eluting with 0-100% ethyl acetate/methylene chloride. The fractions corresponding to the desired Boc protected product were combined and the solvent removed in vacuo. This residue was redissolved in TFA (3 mL) and allowed to stand at room temperature for 10 minutes. The solvent was removed in vacuo and the residue was purified on silica gel (4 g) column eluting with 0-10% methanol/methylene chloride gradient. The pure fractions were combined, treated with 1N hydrochloric acid and the solvent removed in vacuo to provide title compound. 1H NMR (DMSO-d6): δ 13.7 (s, 1H), 8.58 (s, 1H), 8.52 (d, 1H, J=4.4 Hz), 8.16 (d, 1H, 8.0 Hz), 7.74 (dd, 1H, J=1.5 Hz), 7.63 (d, 1H, J=8.8 Hz), 7.47 (d, 1H, J=8.5 Hz), 7.39 (dd, 1H, J=1.5 Hz), 7.29 (dd, 1H, J=2 Hz), 7.19 (dd, 1H, J=4.5 and 8.1 Hz) and 5.92 (s, 2H) ppm. LRMS (M+1)=434.7

情報源と証拠