Potassium Carbonate → 3-[5-(Azetidine-1-carbonyl)-3-chloro-pyridin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide

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A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (136 mg, 0.4 mmol), azetidin-1-yl-(5,6-dichloropyridin-3-yl)methanone (Intermediate 21) (103 mg, 0.44 mmol) and potassium carbonate (111 mg, 0.8 mmol) in DMA (5 mL) was stirred at 120° C. for 2 hours. The solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (40 mL) washed with water (2×20 mL), brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica, eluting with a gradient of 0-4% methanol in DCM to afford the product (188 mg, 87%). 1H NMR δ (300 MHz, CDCl3) 2.16-2.29 (m, 1H), 2.40 (quintet, 2H), 2.50-2.72 (m, 4H), 2.95 (s, 3H), 3.36-3.58 (m, 2H), 4.18-4.42 (m, 4H), 4.95 (t, 1H), 7.15 (s, 1H), 7.37 (s, 1H), 7.55 (s, 1H), 8.15 (s, 2H), 8.25 (s, 1H), 8.55 (s, 1H), 9.54 (s, 1H); m/z 537 (M+H)+.

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