1,4-Dioxane → HCID 53377726, compound

Participants

Reaction Conditions

Reaction Steps

A small vial was charged with 2-(1-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol from Example 8 (0.070 g, 0.17 mmol), 2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole (0.042 g, 0.21 mmol), XPhos (0.012 g, 0.026 mmol) and Potassium phosphate (0.110 g, 0.519 mmol). Dry 1,4-dioxane (1.9 mL, 0.024 mol) was added. The whole was sparged with nitrogen for 3 min. Tris(dibenzylideneacetone)dipalladium(0) (0.012 g, 0.013 mmol) was added under nitrogen. The vial was sealed and heated at 155° C. (heating block temp) for 4 h. LC/MS indicates complete reaction. The solution was diluted with water and extracted with dichloromethane 3 times. The combined organics were washed with brine and dried over sodium sulfate. The material was purified by reverse phase HPLC to give 51.3 mg (53% yield) of 173 as a white solid. LCMS (MH+)=570.3. 1H NMR (400 MHz, DMSO) δ 8.25-8.15 (m, 2H), 7.91 (d, J=8.7 Hz, 1H), 7.76 (d, J=7.5 Hz, 1H), 7.42-7.31 (m, 2H), 4.65 (q, J=10.7 Hz, 2H), 4.90-4.25 (br m, 4H), 4.05 (s, 1H), 3.88-3.80 (m, 4H), 3.74 (s, 2H), 2.92 (d, J=11.1 Hz, 2H), 1.99 (t, J=11.1 Hz, 2H), 1.67 (d, J=11.2 Hz, 2H), 1.37-1.23 (m, 2H), 1.22-1.12 (m, 1H), 1.04 (s, 6H)

Provenance & Evidence