Palladium catalyzed reactions have become prominent reactions for creating C-N bonds and are widely used in the synthesis of pharmaceuticals. The reaction progress is substrate specific and supported using specific phosphine ligands with unique electronic and steric properties. In this study, multiple phosphine ligands were investigated in the palladium catalyzed coupling of aliphatic and aromatic amines to a bromine containing benzodiazepine. Our results showed of 5% Pd2(dba)3 in conjunction with 10% Xphos was the best catalytic system when carried out in toluene. Full conversion with aniline was observed within 2 h at 90°C. The addition of THF increased the solubility of some products and improved their yields. In general, yields ranged from 26% to 89%. For ortho substituted aromatic amines, we did not observe reduced product formation due to steric hinderance. All products were analyzed and characterized using liquid chromatography-mass spectrometry and NMR spectroscopy.