Nitrogen → HCID 21928167, compound

Participants

Reaction Conditions

Reaction Steps

An N2-purged suspension of 3-Amino-6-{4-[2-(5-bromo-pyridin-2-yl)-2-hydroxy-ethylamino]-piperidin-1-yl}-4-trifluoromethyl-thieno[2,3-b]pyridine-2-carboxylic acid amide (150 mg, 0.268 mmol), bis(pinacolato)diboron (153 mg, 0.590 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-CH2Cl2 complex (33 mg, 0.040 mmol), and potassium acetate (133 mg, 1.34 mmol) in dry DMF (4 ml) was heated at 80° C. for 2.5 h. The crude reaction mixture was then added directly via syringe to a stirring, N2-purged suspension of 6-bromo-2-oxindole (65 mg, 0.295 mmol), tetrakis(triphenylphosphine)palladium(0) (47 mg, 0.040 mmol), and potassium carbonate (74 mg, 0.536 mmol) in dry DMF (6 ml) and water (2 ml) at rt. The sealed mixture was heated to 85° C. for 4 h. The crude reaction was applied direcly to a SiO2 column and purified (0–25% MeOH/CH2Cl2 with NH4OH). Fractions containing desired product were pooled and concentrated. The yellow residue was dissolved in 2 ml DMF and applied to a 2 mm prep plate (Merck) eluting with 10% MeOH/CH2Cl2 with 1% NH4OH. The yellow product crystallized at the origin and the impurities were removed by being carried up the plate. The recovered yellow residue was dissolved in 1 ml DMF, 2 ml MeOH, 5 ml EtOAc, and 5 ml CH2Cl2 and crystallized by the addition of 30 ml hexanes to give 20.5 mg, 11.9% of 3-Amino-6-(4-{2-hydroxy-2-[5-(2-oxo-2,3-dihydro-1H-indol-6-yl)-pyridin-2-yl]-ethylamino}-piperidin-1-yl)-4-trifluoromethyl-thieno[2,3-b]pyridine-2-carboxylic acid amide product. ES+ 612.4 m/z (MH+).

Provenance & Evidence