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

Temperatur

70 °C

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.

1. temperatureto cool
2. extractionextracted with chloroform and EtOAc
3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto afford the crude product (386 mg, 122% yield) as a viscous oil
7. stirringAfter stirring for 2 hours at ambient temperature the mixture
8. concentrationwas concentrated
9. additionThe residue was treated with excess (20 ml) saturated aqueous sodium bicarbonate solution
10. extractionthe resulting mixture was extracted with chloroform and EtOAc
11. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
12. concentrationconcentrated
13. customto afford a viscous oil
14. customThe oil was purified by column chromatography on silica gel (elution with 7 N NH3/MeOH-chloroform)

ORD-Eintrag

ord-595d7a6a1ef3479c85794158e78f1419

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08138181B2