In this work, we followed up on a series of pseudo-irreversible covalent carbamate hBChE inhibitors, and determined the carbamate warhead SARs and steric requirements/constraints for the carbamoylation of the catalytic Ser198 with dialkylcarbamoyl moieties. The covalent mechanism of binding was sequentially confirmed by IC 50 time-dependency profiles, kinetic analysis through k obs determination and recovery-upon-dilution experiments, LC-MS, and finally by X-ray crystal structure determination. For the selected 7-substituted carbamate inhibitor 6, the mass increase corresponding to the dimethylcarbamoyl moiety was observed in whole protein LC-MS experiment, and the crystal structure of dimethylcarbamoylated enzyme together in complex with the leaving group 5 was obtainedmaking this the first known crystal structure of the dimethylcarbamoylated BChE.