2-Bromo-5-methylpyridine → 1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyridin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

1-((2S,4R)-4-Amino-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 7) (100 mg, 0.304 mmol), 2-bromo-5-methylpyridine (105 mg, 0.609 mmol), Davephos (23.97 mg, 0.061 mmol), Pd2(dba)3 (27.9 mg, 0.030 mmol) and sodium tert-butoxide (58.5 mg, 0.609 mmol) were combined in 1,4-dioxane (3 ml) and the mixture degassed over a period of 20 min. The mixture was heated at 120° C. for 25 min (microwave). The reaction mixture was partitioned between water (100 ml) and DCM (3×100 ml). The organics were combined, dried (hydrophobic frit) and evaporated under vacuum. The residual brown oil was dissolved in DMSO (2×1 ml) and purified by MDAP (HpH ×2). The solvent was evaporated under vacuum to give 1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyridin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone (49 mg, 0.117 mmol, 38% yield) as a yellow glass. LCMS (formate), Rt 0.61 min, MH+ 420.

Provenance & Evidence