Sodium Bicarbonate → N-(2-chloro-5-(4-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzene-sulfonamide

Participants

Reaction Steps

A mixture of 6-chloro-4-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidine (Intermediate 6) (0.03 g, 0.108 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.046 g, 0.108 mmol), PdCl2(dppf)-CH2Cl2Adduct (8.79 mg, 10.76 μmol) and sodium bicarbonate (0.215 ml, 0.215 mmol) in dioxane (0.538 ml) was refluxed for 3 hours. After cooling to room temperature, the reaction mixture was filtered through a Celite pad and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by prep TLC (EtOAc:MeOH=10:1) to give N-(2-chloro-5-(4-(1-methylpiperidin-4-yloxy)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzene-sulfonamide (0.02 g, 34%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.10-2.22 (2H, m), 2.37 (2H, s), 2.62 (3H, s), 2.88-2.95 (2H, m), 3.13-3.17 (2H, m), 5.64 (1H, brs), 6.86-6.94 (2H, m), 7.86-7.92 (1H, m), 8.21 (1H, d, J=9.2 Hz), 8.34 (1H, d, J=8.8 Hz), 8.79 (1H, d, J=2.0 Hz), 8.82 (1H, s), 8.91 (1H, brs). m/z=547.4 [M+1]+.

Provenance & Evidence