Sodium Carbonate → HCID 68424147, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 9-bromo-5-{[2,6-dichloro-4-(1-hydroxyethyl)phenyl]amino}benzo[c]-2,6-naphthyridin-1(2H)-one (Examples 94 and 95, Step 3) (300 mg, 0.63 mmol) in DMF (3 mL) were added sodium carbonate (0.3 mL, 2 M) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (208 mg, 1.00 mmol), followed by tetrakis(triphenylphosphine)palladium (0) (145 mg, 0.13 mmol). The solution was degassed by bubbling nitrogen gas for 5 min. The reaction vessel was sealed and heated to 80° C. overnight. The reaction mixture was extracted with 3:1 (CHCl3/iPrOH) and water. The organic layers were combined and dried with MgSO4, filtered, and concentrated under reduced pressure. Purification with column chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) afforded 5-{[2,6-dichloro-4-(1-hydroxyethyl)phenyl]amino}-9-(1-methyl-1H-pyrazol-4-yl)benzo[c]-2,6-naphthyridin-1(2H)-one as racemates. The enantiomers were separated using a Chiralpak AD 10 mm×250 mm column with 40% iPrOH/60% Heptane with a flow rate of 10 ml/min in a 25 min run. The first enantiomer has a retention time of 8.47 min and the second enantiomer has a retention time of 11.68 min.

Provenance & Evidence