Potassium Carbonate → 1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid {(rac)-3-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-6,7-dihydro-5H-[1]pyrindin-7-yl}-amide

Participants

Reaction Conditions

Reaction Steps

1-(2,2,2-trifluoro-acetylamino)-cyclopropanecarboxylic acid ((rac)-3-bromo-6,7-dihydro-5H-[1]pyrindin-7-yl)-amide (intermediate A-5) (0.2 g, 510 μmol), potassium acetate (150 mg, 1.53 mmol) and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (155 mg, 612 μmol) were dissolved in DMSO (8.0 ml). The reaction vessel was closed and evacuated, then charged with argon; this procedure was repeated five times. After 10 minutes (1,1′-bis-diphenylphosphino)-ferrocene)palladium-(II)dichloride (1:1 complex with CH2Cl2) (18.7 mg, 25.5 μmol, eq: 0.05) was added and the reaction mixture was stirred at 90° C. for 1.5 hours. After cooling to RT, potassium carbonate (141 mg, 1.02 mmol), dissolved in water (1.0 ml) and 3-(2-bromo-4-chloro-6-fluoro-phenyl)-5-methyl-[1,2,4]oxadiazole (intermediate B-2) (164 mg, 561 μmol) were added, followed by (1,1′-bis-diphenylphosphino)-ferrocene)palladium-(II)dichloride (1:1 complex with CH2Cl2) (18.7 mg, 25.5 μmol, eq: 0.05). This reaction mixture was stirred at 80° C. for 3 hours, then poured into H2O (50 ml) and extracted with CH2Cl2 (3×25 ml). The organic layers were dried over MgSO4, filtered and concentrated in vacuo to give a crude product (0.364 g), which was purified by flash chromatography (silica gel, 20 g, 0% to 2% MeOH in CH2Cl2) to yield the title compound (0.134 g, 50%) as light grey solid. MS: 524.1 (MH+, 1Cl).

Provenance & Evidence