Pyridine → 3-{[6-(Azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-N-(5-methylpyrazin-2-yl)-5-[(phenylmethyl)oxy]benzamide

Participants

Reaction Steps

1-Chloro-N,N,2-trimethyl-prop-1-en-1-amine (2.4 mL, 18 mmol) was added to a solution of 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-phenylmethoxy-benzoic acid (Intermediate 3) (6.19 g, 15 mmol) in DCM (100 mL) and stirred at ambient temperature for 30 minutes. Further 1-chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.24 mL, 1.8 mmol) was added and stirring continued for 20 minutes. 5-Methylpyrazin-2-amine (CAS no. 5521-58-4) (3.34 g, 31 mmol) and pyridine (2.5 mL, 31 mmol) were added and the reaction stirred for a further 16 hours. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (350 mL), washed with water (2×100 mL) and brine (100 mL), dried (MgSO4), and evaporated under reduced pressure. The residue was purified by flash chromatography, eluting with a gradient of 50-75% ethyl acetate in isohexane, to afford the product (4.01 g, 53%). 1H NMR δ (400 MHz, CDCl3) 2.28 (quintet, 2H), 2.49 (s, 3H), 4.18 (t, 2H), 4.63 (t, 2H), 5.05 (s, 2H), 6.78 (s, 1H), 7.10 (s, 1H), 7.25-7.37 (m, 7H), 8.04 (d, 1H), 8.07 (s, 1H), 8.25 (s, 2H), 9.46 (s, 1H); m/z 496 (M+H)+.

Provenance & Evidence