Hydrochloric Acid → 6-((8-Fluoro-6-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinoline

Participants

Reaction Conditions

Reaction Steps

6-((6-chloro-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinoline. A mixture of 1-(5-chloro-3-fluoropyridin-2-yl)hydrazine (500 mg, 3095 μmol) and methyl 2-(quinolin-6-yl)acetate (600 mg, 2982 μmol) in HCl (conc., 600 μL, 7200 μmol) was heat at 100° C. for 20 min. The mixture was then heated in a microwave at 180° C. for 40 min. The mixture was quenched with NaOH (5 N, 1.5 mL) and the suspension was filtered and washed with H2O. The resulting brown solid is mostly the desired product. The solid was then triturated with NaOH (5 N, 1 mL), filtered, and washed with H2O. LCMS (ESI pos. ion): calc'd for C16H10ClFN4: 312.0; found: 313.1 (M+1). 2) 6-((8-fluoro-6-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinoline. A mixture of Pd(OAc)2 (6.46 mg, 28.8 μmol), potassium phosphate (367 mg, 1727 μmol), phenylboronic acid (211 mg, 1727 μmol), dicyclohexyl(2-(2,4,6-triisopropylcyclohexa-1,3-dienyl)phenyl)phosphine (27.6 mg, 57.6 μmol), and 6-((6-chloro-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinoline (180 mg, 576 μmol) in dioxane (6 mL)-H2O (2 mL) was heated to 100° C. under nitrogen for 20 h. The mixture was cooled to rt and partitioned between H2O and CH2Cl2. The organic layer was dried over MgSO4 and concentrated. The residual was purified on silica using MeOH in DCM (0-5%) to give a pink solid. This solid was triturated with hexane-EtOAc-DCM (hot) to give a brown solid (105 mg). LCMS (ESI pos. ion): calc'd for C22H15FN4: 354.1; found: 355.2 (M+1).

Provenance & Evidence