Synthesis of Biphenyl-Pyridopyrimidine Amide Derivative

Example 16

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A mixture of 6-(2-chloro-2′-methyl-3′-((2-methylpyrido[3,2-d]pyrimidin-4-yl)amino)-[1,1′-biphenyl]-3-yl)-2-methoxynicotinaldehyde (50 mg, 0.10 mmol), 2-aminoacetamide hydrogen chloride (30 mg, 0.27 mmol), Et₃N (0.070 mL, 0.50 mmol) and AcOH (0.080 mL, 1.37 mmol) in DCM (2 mL) was stirred for 1.5 h at room temperature. To the mixture was added NaBH(OAc)₃ (80 mg, 0.36 mmol). After stirring for an additional 1.5 h, the reaction was quenched with sat. NaHCO₃ and extracted with DCM. The organic layer was separated, dried over Na₂SO₄, concentrated in vacuo and purified by silica gel chromatography to afford 2-(((6-(2-chloro-2′-methyl-3′-((2-methylpyrido[3,2-d]pyrimidin-4-yl)amino)-[1,1′-biphenyl]-3-yl)-2-methoxypyridin-3-yl)methyl)amino)acetamide. ¹H NMR (400 MHz, CDCl₃) δ 9.23 (s, 1H), 8.72 (dd, J=4.0, 1.2 Hz, 1H), 8.58 (d, J=8.4 Hz, 1H), 8.09 (dd, J=8.4, 1.6 Hz, 1H), 7.70-7.65 (m, 1H), 7.63 (dd, J=8.0, 1.6 Hz, 1H), 7.55 (d, J=7.6 Hz, 1H), 7.44-7.37 (m, 2H), 7.30 (dd, J=5.6, 2.0 Hz, 1H), 7.32-7.24 (m, 2H), 7.06 (d, J=7.2 Hz, 1H), 4.03 (s, 3H), 3.79 (s, 2H), 3.31 (s, 2H), 2.36 (s, br, 2H), 2.26 (s, 3H), 2.04 (s, 3H). MS: (ES) m/z calculated C₃₀H₂₉ClN₇O₂ [M+H]⁺ 554.2, found 554.1.