Compound 27 possesses a γ-lactam structure, which is a known KAc binding motif, derived from Nmethyl-2-pyrrolidone (NMP). We have previously shown that the γ-lactam-based solvent NMP is a weak bromodomain ligand. Hilton-Proctor et al. subsequently used the NMP motif as the basis for developing higher affinity bromodomain ligands. Given these observations we designed the clickable probes based on compound 27 so as to leave the γ-lactam unaltered. In compound 41, a N-methylpropargylamine is used to add both the electrophile and the alkyne on to the aniline nitrogen (Scheme 2A). In compound 42, the aniline nitrogen is functionalized as an acrylamide, while a propargyl group is attached to the phenolic oxygen to provide the click handle (Scheme 2A). Compound 43 was purchased and reacted with (E)-4-bromocrotonic acid in the presence of oxalyl chloride and DMF to give 44. Treatment of 44 with KI resulted in halogen exchange followed by substitution with N-methylpropargylamine to give 41 (Scheme 2B). To synthesize 42, compound 43 was demethylated using BBr3, giving 45, which was selectively Nacylated by treatment with acryloyl chloride to yield 46. Reaction of 46 with propargyl bromide afforded the desired product 42 (Scheme 2C).