2-Ethylbenzimidazole → 3-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (3.0 g, 6.62 mmol), 2-ethylbenzimidazole (1.16 g, 7.94 mmol), tris(dibenzylideneacetone)dipalladium (152 mg, 0.17 mmol), XPhos (316 mg, 0.66 mmol) and K3PO4 (2.81 g, 13.24 mmol) in dioxane (80 mL) was purged with N2 then heated at 90° C. for 22 h before further tris(dibenzylideneacetone)dipalladium (152 mg, 0.17 mmol) and XPhos (316 mg, 0.66 mmol) were added. The resulting mixture was heated at 100° C. for 65 h then diluted with 2-methyl THF and filtered through a silica plug. The filtrate was washed with H2O and brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, EtOAc:cyclohexane, 20-85%) affording 3-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (3.15 g, 85%). LCMS (method H): RT 2.87 min, [M+H]+ 563.5

Provenance & Evidence