反应详情

温度

120 °C

A mixture of 4-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)piperidine-1-carboxylic acid tert-butyl ester (375 mg, 0.858 mmol), 2-ethylbenzimidazole (151 mg, 1.03 mmol), Xphos (43 mg, 0.09 mmol) and Cs2CO3 (421 mg, 1.29 mmol) in dioxane (5 mL) was degassed with nitrogen bubbling for 15 minutes. Tris(dibenzylideneacetone)dipalladium (20 mg, 0.022 mmol) was added and the mixture was heated to 120° C. for 20 hours. The reaction mixture was diluted with EtOAc, filtered, concentrated in vacuo and purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 40-90%) affording 647 (390 mg, 83%). LCMS: RT 4.54 min, [M+H]+ 547.24 1H NMR (400 MHz, DMSO): δ 8.00-7.99 (m; 1 H); 7.68-7.60 (m; 1 H); 7.25-7.24 (m; 2 H); 4.45-4.12 (m; 4 H); 4.12-4.01 (d; J=13.26 Hz, 2 H); 3.85-3.70 (m; 6 H); 3.25-3.10 (m, 4 H); 3.04-2.82 (m, 2 H); 2.00-1.90 (d; J=13.26 Hz, 2 H); 1.76-1.59 (m, 2); 1.43 (s; 9 H); 1.35 (t, J=7.44 Hz, 3 H).

1. customwas degassed with nitrogen bubbling for 15 minutes
2. filtrationfiltered
3. concentrationconcentrated in vacuo
4. custompurified by column chromatography (Si—PCC, EtOAc:cyclohexane, 40-90%)