Sodium Bicarbonate → Tert-butyl 2-({5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-1,1'-biphenyl-4-yl}carbonyl)hydrazinecarboxylate

Participants

Reaction Conditions

Reaction Steps

N-Cyclopropyl-5-fluoro-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 32) (3.27 g), 4-bromo-benzoic acid N′-(2,2-dimethyl-propionyl)-hydrazide (Intermediate 31) (3.39 g), tetrakis(triphenylphosphine)palladium (238 mg) and aqueous sodium hydrogen carbonate (1M, 21.6 ml) were mixed in propan-2-ol (20 ml) and heated at 90° C. under nitrogen for 18 hours. The cooled reaction mixture was reduced to dryness under vacuum, the residue partially dissolved in ethyl acetate and filtered. The filtrate was absorbed onto silica and purified by chromatography on silica biotage columns (2×100 g), eluting with ethyl acetate/cyclohexane (2:3). The product fractions were reduced to dryness under vacuum to give tert-butyl 2-({5′-[(cyclopropylamino)carbonyl]-3′-fluoro-2′-methyl-1,1′-biphenyl-4-yl}carbonyl)hydrazinecarboxylate.

Provenance & Evidence