Cesium carbonate → tert-butyl3-{[4-chloro-3-(3-chloro-5-cyanophenoxy)-5-fluorophenoxy]methyl}-6-fluoro-1H-pyrazolo[3,4-b]pyridine-1-carboxylate

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Reaction Steps

Under a nitrogen atmosphere, 3-chloro-5-(2-chloro-3-fluoro-5-hydroxyphenoxy)benzonitrile (50-5) (150 mg, 0.503 mmol) was dissolved in NMP (4 mL, 0.1 M). Next, Cs2CO3 (164 mg, 0.503 mmol) was added and the reaction was allowed to stir at room temperature for 15 minutes. Then, tert-butyl-3-(bromomethyl)-6-fluoro-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (37-5) (166 mg, 0.503 mmol, prepared using the procedure set forth in Example 37) was added to the reaction. The reaction was stirred at room temperature for 2 hours. It was then diluted with EtOAc (4 mL). It was partitioned with water (3 mL) and then extracted with EtOAc (3×4 mL). The organic extracts were then washed with water (3×4 mL) and brine (1×4 mL), dried over sodium sulfate and concentrated. Silica gel chromatography (1%-20% EtOAc/Hexanes) gave tert-butyl3-{[4-chloro-3-(3-chloro-5-cyanophenoxy)-5-fluorophenoxy]-methyl}-6-fluoro-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (50-6) (230 mg, 85%). LCMS (ES) m/z 446.9 (M-BOC)+.

Provenance & Evidence