反应详情

A mixture of 6-chloro-N-cyclopropylpyrido[3,2-d]pyrimidin-4-amine (Intermediate 20) (0.060 g, 0.272 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.141 g, 0.326 mmol), PdCl2(dppf)-CH2Cl2 Adduct (2.221 mg, 2.72 μmol) and 1 N aq. sodium bicarbonate (0.544 ml, 0.544 mmol) in dioxane (1.40 ml) subjected to microwave irradiation for 1 hour at 110° C. After cooling to room temperature, the reaction mixture was filtered through Celite and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give N-(2-chloro-5-(4-(cyclopropylamino)pyrido[3,2-d]pyrimidin-6-yl) pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.070 g, 53%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 0.78-0.82 (2H, m), 1.04-1.09 (2H, m), 3.08-3.13 (1H, m), 6.95-7.02 (2H, m), 7.30 (1H, brs), 7.85-7.91 (1H, m), 8.08 (1H, d, J=8.8 Hz), 8.24 (1H, d, J=8.8 Hz), 8.67 (1H, d, J=2.0 Hz), 8.76 (1H, s), 8.81 (1H, d, J=2.0 Hz). m/z=489.2 [M+1]+.

1. customirradiation for 1 hour at 110° C
2. filtrationthe reaction mixture was filtered through Celite
3. washwashed with CH2Cl2
4. concentrationThe filtrate was concentrated in vacuo
5. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)