反应详情

温度

110 °C

A mixture of 3-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-methoxypiperidine-1-carboxylic acid tert-butyl ester (3.0 g, 6.42 mmol), 2-isopropylbenzimidazole (1.24 g, 7.71 mmol), tris(dibenzylideneacetone)dipalladium (150 mg, 0.16 mmol), XPhos (306 mg, 0.64 mmol) and Cs2CO3 (3.14 g, 9.64 mmol) in dioxane (50 mL) was purged with argon then heated at 110° C. for 16 h. The reaction mixture was partitioned between EtOAc and H2O, the organic phase washed with brine then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 30-70%) affording 3-[2-(2-Isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-methoxypiperidine-1-carboxylic acid tert-butyl ester (2.47 g, 65%). LCMS (method A): RT 3.52 min, [M+H]+ 591.5

1. customwas purged with argon
2. customThe reaction mixture was partitioned between EtOAc and H2O
3. washthe organic phase washed with brine
4. dry with materialthen dried (Na2SO4)
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 30-70%)