Sodium hydride → tert-Butyl 4-(6-bromothiazolo[4,5-b]pyridin-2-yloxy)piperidine-1-carboxylate

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Reaction Steps

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (0.88 g, 4.37 mmol) in DMF (8.7 mL) was added NaH (0.121 g, 4.81 mmol) at 0° C. Upon completion of addition, the mixture was warmed to rt until the mixture became a clear solution. In a separate flask, 6-bromo-2-chlorothiazolo[4,5-b]pyridine hydrochloride (0.5 g, 1.748 mmol) was suspended in DMF (8.74 mL) and the above sodium salt solution was transferred into the thiazolepyridine suspension via cannulation. The resulting mixture was then heated in a 50° C. oil bath. After 4 h, the reaction mixture was analyzed by HPLC, which indicated the reaction was complete. The reaction mixture was cooled to rt, and then quenched with NaHCO3 (saturated aq, 10 mL). The resulting mixture was extracted with EtOAc (3×5 mL) and the combined organic layers were dried (Na2SO4), filtered, and concentrated to yield the crude product. The crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc) to give Compound 21B as a white solid (150 mg, 21% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 8.54 (d, J=2.2 Hz, 1H), 8.08 (d, J=2.2 Hz, 1H), 5.43-5.52 (m, J=8.0, 8.0, 4.0, 3.9 Hz, 1H), 3.70-3.84 (m, 2H), 3.24-3.34 (m, 2H), 2.07-2.17 (m, 2H), 1.80-1.92 (m, J=12.7, 8.5, 8.5, 4.1 Hz, 2H), 1.46 (s, 9H). LC/MS (m/z)=415 (M+H)+.

Provenance & Evidence