Toluene → HCID 70976544, compound

Participants

Reaction Conditions

Reaction Steps

to a flask charged with 1-((2S,4R)-2-methyl-4-((5-nitropyridin-2-yl)amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 24)(1.03 g, 2.277 mmol), methyl 6-bromonicotinate (0.541 g, 2.505 mmol), potassium carbonate (0.944 g, 6.83 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.263 g, 0.228 mmol) was added a previously degassed mixture of toluene (10 mL) and ethanol (10 mL). The resulting mixture was stirred at 90° C. under nitrogen. After 3 h, further portions of methyl 6-bromonicotinate (0.271 g, 1.252 mmol), potassium carbonate (0.472 g, 3.42 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.132 g, 0.114 mmol) were added and reaction mixture heated for a further 4 h. The reaction was cooled to room temperature and concentrated in vacuo. The crude residue was partitioned between EtOAc and water, the phases separated and aqueous phase extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by chromatography, eluting with an EtOAc/hexanes gradient gave ethyl 6-((2S,4R)-1-acetyl-2-methyl-4-((5-nitropyridin-2-yl)amino)-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate (740 mg, 1.556 mmol, 68.3% yield) as a yellow foam.

Provenance & Evidence