Trifluoroacetic acid → 2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)-8-(pyrrolidin-3-ylmethoxy)quinoline

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Reaction Conditions

Reaction Steps

To a solution of 2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol [prepared as in Example 16; 204 mg, 0.61 mmol] in anhydrous DMA (5 mL) was added cesium carbonate (0.60 g, 1.8 mmol) followed by tert-butyl 3-((methylsulfonyloxy)methyl)pyrrolidine-1-carboxylate (221 mg, 0.79 mmol). The heterogeneous mixture was stirred at 70° C. for 20 hours and allowed to cool. The mixture was treated with water (50 mL) and extracted with chloroform and EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated to afford the crude product (386 mg, 122% yield) as a viscous oil. MS ESI (+) m/z 519.1 (M+1) detected. The oil (315 mg) was dissolved in CH2Cl2 (2 mL) and treated with TFA (1 mL). After stirring for 2 hours at ambient temperature the mixture was concentrated. The residue was treated with excess (20 ml) saturated aqueous sodium bicarbonate solution, and the resulting mixture was extracted with chloroform and EtOAc. The combined organic extracts were dried over anhydrous Na2SO4 and concentrated to afford a viscous oil. The oil was purified by column chromatography on silica gel (elution with 7 N NH3/MeOH-chloroform) to provide the title compound (74 mg, 36% yield over two steps) as a solid. MS ESI (+) m/z 419.3 (M+1). detected.

Provenance & Evidence