Cesium carbonate → 2-[[2-Chloro-5-(trifluoromethyl)-4-pyridyl]amino]-5-fluoro-n-methoxy-benzamide

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Using the procedure in example 15.01, 2-amino-5-fluorobenzoic acid (1.5 g, 9.67 mmol) was converted into 6-fluoro-1H-3,1-benzoxazine-2,4-dione (1.2 g, 68.5%) as an pale yellow solid; and 6-fluoro-1H-3,1-benzoxazine-2,4-dione (1.05 g, 5.80 mmol) converted into 2-amino-5-fluoro-N-methoxybenzamide (0.344 g, 32.2%) as a yellow pale solid after purification by 2 flash chromatographies on silica gel (eluting with 0 to 50% EtOAc in DCM; eluting with 20% EtOAc in DCM). NMR Spectrum: (DMSOd6) 3.68 (s, 3H), 6.19 (bs, 2H), 6.72 (dd, 1H), 7.07 (ddd, 1H), 7.15 (dd, 1H), 11.48 (bs, 1H) 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (0.502 g, 1.63 mmol), 2-amino-5-fluoro-N-methoxybenzamide (0.344 g, 1.68 mmol), palladium(II) acetate (0.029 g, 0.13 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.151 g, 0.26 mmol) and cesium carbonate (0.638 g, 1.96 mmol) were weighed out in a microwave vial and sealed. Dioxane (10.3 ml) was added and argon bubbled through the reaction mixture followed by stirring at 90° C. for 5 hours. The reaction mixture was allowed to cool to room temperature, silica gel was added and the mixture was concentrated to afford the crude, which was purified by flash chromatography on silica gel eluting with 20 to 50% EtOAc. The solvent was evaporated to dryness to afford 2-[[2-chloro-5-(trifluoromethyl)-4-pyridyl]amino]-5-fluoro-N-methoxy-benzamide (0.240 g, 40%) as an yellow oil which crystallised on standing. NMR Spectrum: (DMSOd6) 3.62 (s, 3H), 6.85 (s, 1H), 7.43-7.51 (m, 2H), 7.60 (dd, 1H), 7.44 (s, 1H), 9.37 (bs, 1H), 11.88 (bs, 1H); Mass spectrum: MH+ 364

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