Carbonate Ion → Methyl 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoate (Intermediate 8) (265 mg, 1.0 mmol), azetidin-1-yl-(5-chloropyrazin-2-yl)methanone (Intermediate 32) (198 mg, 1.0 mmol) and polymer supported-carbonate (690 mg, 2.0 mmol) in DMA (5 mL) was stirred at 100° C. for 1 hr. The mixture was filtered and the DMA was removed under reduced pressure. The residue was dissolved in ethyl acetate (50 mL), washed with saturated sodium bicarbonate (10 mL), water (20 mL) and brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by chromatography on silica eluting with 20-100% ethyl acetate in isohexane then 10% Methanol in DCM to give afford the product (304 mg, 71%). 1H NMR δ (300 MHz, CDCl3) 2.13-2.27 (m, 1H), 2.31-2.44 (m, 2H), 2.53-2.66 (m, 1H), 2.94 (s, 3H), 3.35-3.58 (m, 2H), 3.90 (s, 3H), 4.26 (t, 2H), 4.68 (t, 2H), 4.93 (t, 1H), 7.14 (s, 1H), 7.46 (s, 1H), 7.60 (s, 1H), 8.31 (s, 1H), 8.84 (s, 1H); m/z 427 (M+H)+

Provenance & Evidence