Trifluoroacetic acid → 3-(6-Chloro-1-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

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Reaction Steps

Tert-butyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate (0.20 g, 0.45 mmol) was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (2 mL). When LC/MS analysis revealed the deprotection of the Boc group, the mixture was concentrated to dryness under reduced pressure. Diethyl ether was evaporated three times from the crude material in order to afford a solid residue. The trifluoroacetate salt was dissolved in dichloromethane (10 mL) and then treated with triethylamine (0.18 mL). The mixture was concentrated to dryness under reduced pressure. The residue was taken up in dichloromethane (10 mL) and treated with 3-pyridinecarboxaldehyde (0.064 mL). The mixture was allowed to stir for 10 minutes before the addition of sodium triacetoxyborohydride (0.15 g, 0.68 mmol). After stirring overnight, the mixture was diluted with dichloromethane and washed with 1 M aqueous sodium hydroxide solution. The aqueous phase was back extracted once with dichloromethane and then the combined organics were dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure. 3-(6-Chloro-1-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (0.20 g, 100%) was thus obtained as a yellow crystalline solid. MS (ES+): 440.0, 441.2 (M+H)+

Provenance & Evidence