Diisopropylethylamine → 6-cyclopentyl-N-[(5,6-dimethoxypyridin-2-yl)methyl]-5'-methyl-3,3'-bipyridine-5-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a suspension of sodium 6-cyclopentyl-5′-methyl-3,3′-bipyridine-5-carboxylate (6-3, 0.022 g, 0.078 mmol, 1.0 equiv) in acetonitrile (0.8 mL) was added 1-(5,6-dimethoxypyridin-2-yl)methanamine (11-6, 0.039 g, 0.234 mmol, 3.0 equiv), 1-propylphosphonic acid cyclic anhydride (0.149 g, 0.234 mmol, 3.0 equiv, 50 weight percent in EtOAc), and diisopropylethylamine (0.060 g, 0.47 mmol, 6.0 equiv) and the system was heated to 40° C. for 24 h. The reaction mixture was cooled and diluted with ethyl acetate (30 mL). The reaction mixture was washed with saturated sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (1×10 mL), dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (0 to 40% methanol in EtOAc, silica) followed by reverse phase chromatography (5 to 65% acetonitrile in water, 0.1% TFA buffer) to afford the desired product (6-4) as a white solid after free-basing and concentration. 1H NMR (500 MHz, CDCl3) δ 8.83 (d, J=2.5 Hz, 1H), 8.62 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 7.84 (d, J=2.0 Hz, 1H), 7.65 (s, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.90 (d, J=7.5 Hz, 1H), 6.72 (bs, 1H), 4.64 (d, J=5.0 Hz, 2H), 3.97 (s, 3H), 3.88 (s, 3H), 3.52-3.48 (m, 1H), 2.42 (s, 3H), 2.04-1.80 (m, 6H), 1.70-1.60 (m, 2H). HRMS [M+H] C25H28N4O3 calc'd 433.2234, found 433.2226.

Provenance & Evidence