Dimethylacetamide → [(1-{2-Fluoro-4-[6-({[3-(trifluoromethyl)phenyl]acetyl}amino)pyridin-3-yl]phenyl}cyclobutyl)oxy]acetic acid

Participants

Reaction Conditions

Reaction Steps

A 4 mL vial was charged with the product from Example 61A (17.7 mg, 0.055 mmol) and the product from Example 60B (16.56 mg, 0.055 mmol), dibasic potassium phosphate (28.5 mg, 0.164 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium (II) dichloride (0.357 mg, 0.546 μmol), N,N-dimethylacetamide (1 ml), ethanol (1.000 mL), and water (0.500 mL). The suspension was stirred and heated to 90° C., whereupon the reaction became homogenous. After heating at 90° C. for 1 hour, the reaction was cooled to room temperature. The reaction was then partitioned between with ethyl acetate (2 mL) and water (2 mL). The layers were separated, and the organic was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase HPLC (mobile phase: 10%-100% acetonitrile in 0.1% trifluoroacetic acid aqueous solution during 60 min, G18 column) to give the title product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.59-1.72 (m, 1H), 1.95-2.07 (m, 1H), 2.38-2.45 (m, 4H), 3.65 (s, 2H), 3.89 (s, 2H), 7.46-7.52 (m, 1H), 7.55-7.67 (m, 5H), 7.73 (s, 1H), 8.11-8.18 (m, 2H), 8.73 (br s, 1H), 10.94 (s, 1H). MS (ESI) m/z 503 [M+H]+.

Provenance & Evidence