Tandem mass spectrum of a farnesyl transferase inhibitor— gas‐phase rearrangements involving imidazole

Compound 1 (1‐(3‐chlorophenyl)‐4‐[1‐(4‐cyanobenzyl)imidazolylmethyl]‐2‐piperazinone hydrochloride) is a farnesyl transferase inhibitor intended for treatment of cancer. A detailed analysis of the electrospray ionization mass spectrometry and tandem mass spectrometry data of protonated 1 shows that in the gas phase, upon collision‐induced dissociation, this ion undergoes complicated rearrangement and fragmentation. These processes include a novel two‐step rearrangement. The first step involves a gas‐phase intramolecular S N 2 reaction that forms an intermediate. The second step consists of three competitive rearrangement/fragmentation pathways of the intermediate, giving rise to protonated 2 , protonated methylene‐imidazole, and a distonic methylimidazole radical cation. Deuterated 1 was studied under the same experimental conditions, and the results strongly support the proposed two‐step rearrangement process. It is noted that the unique structure of 1 , especially the imidazole ring of 1 , plays a critical role in the rearrangement of protonated 1 . Copyright © 2001 John Wiley & Sons, Ltd.