Cesium carbonate → (E)-tert-butyl 3-(6-(but-2-en-2-yl)-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate

Participants

Reaction Conditions

Reaction Steps

tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (250 mg, 0.520 mmol), potassium (Z)-but-2-en-2-yltrifluoroborate (100 mg, 0.617 mmol), sodium 6-(dicyclohexylphosphino)-2′,6′-dimethoxy-[1,1′-biphenyl]-3-sulfonate (107 mg, 0.208 mmol), diacetoxypalladium (23.3 mg, 0.104 mmol), cesium carbonate (254 mg, 0.780 mmol) were combined dry, degassed with N2 and then taken up in DMF (4.7 ml) and water (0.47 ml) and heated to 80° C. for 1 h. The reaction was then concentrated to dryness azeotroping with toluene and the crude mixture was adsorbed onto Celite and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) give the expected product (E)-tert-butyl 3-(6-(but-2-en-2-yl)-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (118 mg, 0.236 mmol, 45% yield) consistent by LCMS and NMR. LC-MS retention time: 2.22 min; m/z (MH+): 501. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (400 MHz, DMSO-d6) δ 8.51-8.43 (m, 1H), 8.10-8.04 (m, 2H), 8.01 (s, 1H), 7.96-7.93 (m, 1H), 7.91-7.87 (m, 1H), 7.68-7.64 (m, 1H), 7.60-7.54 (m, 1H), 7.45-7.37 (m, 2H), 5.44-5.37 (m, 1H), 2.83 (d, J=4.5 Hz, 3H), 1.87-1.82 (m, 3H), 1.59-1.52 (m, 12H).

Provenance & Evidence