Sodium Bicarbonate → N-(2-chloro-5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide

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Reaction Steps

A mixture of N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.02 g, 0.075 mmol) (Intermediate 3), 6-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 1) (0.032 g, 0.075 mmol), sodium bicarbonate (0.151 ml, 0.151 mmol) and PdCl2(dppf)-CH2Cl2Adduct (6.15 mg, 7.53 μmol) in dioxane (0.376 ml) was refluxed for 3 hours. The reaction mixture was cooled to room temperature, filtered through a Celite pad and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=2:1) to give N-(2-chloro-5-(4-(tetrahydro-2H-pyran-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.02 g, 50%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.06-2.12 (2H, m), 2.23-2.30 (2H, m), 3.66-3.76 (2H, m), 4.02-4.17 (2H, m), 5.66-5.72 (1H, m), 6.73-7.01 (2H, m), 7.53 (1H, brs), 7.92-7.98 (1H, m), 8.20 (1H, d, J=8.8 Hz), 8.37 (1H, d, J=8.8 Hz), 8.80 (1H, d, J=2.4 Hz), 8.84 (1H, s), 8.92 (1H, d, J=2.4 Hz). m/z=534.3 [M+1]+.

Provenance & Evidence