Sodium Carbonate → HCID 59824952, compound

Participants

Reaction Conditions

Reaction Steps

Crude N,N-dimethyl-2-oxo-2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)acetamide (592 g, 1.32 mol) from the boronic ester synthesis and 5-bromo-3-(2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine 7 (398.5 g, 1.32 mol) were stirred in acetonitrile (5 L) in 10 L reaction vessel. The solution was stirred and purged with N2 for 30 min. Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (34 g, 40.8 mmol) and Na2CO3(aq) (312.8 g dissolved in 1.36 L H2O) were added. Stirring and purging with N2 continued for 30 min. Thereafter, the solution was heated to 75° C. and stirred under N2 for two days. After the conversion was confirmed to be complete by NMR, H2O (1700 ml) was added and stirring was continued for 10 min. Then heating was stopped and the reaction mixture was filtered over a pad of Celite®. The Celite® pad was washed with a 1:1 mixture of acetonitrile/H2O (3×1000 ml). The filtrate was concentrated until almost acetonitrile had evaporated and a brownish precipitate formed. The concentrated mixture was then extracted with CH2Cl2 (1×3.6 L, 2×1000 ml). The organic layers were combined and dried over Na2SO4, after which the solvent was evaporated in vacuo. The residue was treated with 1800 ml MeOH and sonicated for 15 minutes. The yellowish solid is filtered off and dried in vacuo. This solid is dissolved in a mixture of 10% MeOH in CH2Cl2 and filtered over a SiO2 plug, and washed off using 10% MeOH in CH2Cl2 (±15 L). Yielding after evaporation of the solvent in vacuo ketoamide (380 g, 0.95 mol, 72% over two steps).

Provenance & Evidence