Cesium carbonate → N4-(2,2-dimethyl-3,4-dihydro-3-oxo-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-5-fluoro-N2-(isoquinolin-7-yl)-2,4-pyrimidinediamine

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Reaction Conditions

Reaction Steps

A mixture of 1.6 g 2-chloro-5-fluoro-N4-[2,2-dimethyl-3,4-dihydro-3-oxo-pyrido[3,2-b][1,4]oxazin-6-yl]-4-pyrimidineamine, 800 mg of 7-aminoisoquinoline, 320 mg of palladium acetate, 320 mg of rac-Binap and 3.68 g cesium carbonate in 32 mL of 1,4-dioxane and 8 mL of NMP was heated at reflux at 100° C. overnight under argon. The reaction was cooled, diluted with CH2Cl2/MeOH and filtered. The filtrate was diluted with water and the organic phase evaporated to give the crude product which was dissolved in acetone/MeOH and evaporated onto silica gel. The material was purified by flash chromatography eluting isocratically with CH2Cl2/2 N ammonia solution in MeOH 15:1 to yield 330 mg of the title compound. 1H NMR (DMSO-d6): δ 8.91 (s, 1H), 8.48 (s, 1H), 8.28 (d, 1H), J=5.4 Hz), 8.16 (d, 1H, J=2.1 Hz), 7.82 (m, 2H), 7.68 (d, 1H, J=6 Hz), 7.51 (d, 1H, J=8.1 Hz), 7.30 (d, 1H, J=8.4 Hz), 1.43 (s, 6H); LCMS: purity: 99%; MS (m/e): 432 (MH+)

Provenance & Evidence