Hydrochloric Acid → 2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-8-((trans)-3-fluoropiperidin-4-yloxy)quinoline

Participants

Reaction Conditions

Reaction Steps

Non-racemic (trans)-benzyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-3-fluoropiperidine-1-carboxylate (0.304 g, 0.611 mmol) was dissolved in dioxane (7.6 mL) and treated with 6 M hydrogen chloride (7.64 mL, 45.8 mmol), and the reaction mixture was heated at 100° C. for 15 hours. The reaction was cooled and carefully neutralized with solid NaHCO3. Additional water was added to dissolve the resulting NaCl as the neutralization proceeded. The resulting aqueous layer (pH 8-9) was extracted with methylene chloride and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was chromatographed on SiO2 eluting with a gradient of 2% NH4OH in isopropanol/methylene chloride. The desired product was isolated as a white foam (62.6 mg). MS APCI (+) m/z 364.2 (M+1) detected.

Provenance & Evidence