Sodium Carbonate → 7-(2-{6-[4-(azetidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridin-2-yl}-ethyl)-azepan-2-one

Participants

Reaction Conditions

Reaction Steps

378 mg of 1-(4-bromo-benzenesulfonyl)-azetidine (compound C3) are dissolved in 10 ml of oxygen-free dioxane under an atmosphere of dry nitrogen. Subsequently, 383 mg of bis(pinacolato)diboron, 30 mg of Pd(Cl)2(dppf).CH2Cl2, 23 mg of DPPF (1,1′-bis(diphenylphosphino)-ferrocene), and 403 mg of potassium acetate are added. The reaction mixture is heated at 110° C. for 16 hours during which time the former yellowish suspension becomes black (LC-MS monitoring for boronic ester intermediate). Thereafter, 300 mg of 7-[2-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)-ethyl]-azepan-2-one (compound C1), 2.70 ml of aqueous sodium carbonate solution (strength 2.0 M), and 66 mg of trans-dichloro-bis(tricyclohexyl-phosphine)-palladium(II) are added and the reaction mixture is heated at 110° C. for 72 hours. Subsequently, the mixture is diluted with 50 ml of water and extracted three times each with 100 ml of dichloromethane. The organic layer is separated, dried using Na2SO4 (solid) and concentrated in vacuo. The resulting crude material is purified by chromatography on flash silica gel (eluent gradient: dichloromethane/0-10 vol. % ethanol) to yield 187 mg of the title compound as an oil. ESI-MS: 454.2 (MH+). TLC: Rf=0.29 (dichloromethane/ethanol 10:1 parts by volume).

Provenance & Evidence