Carbon‐13 labeling of ibrutinib for human microdosing

Ibrutinib is an oral medication for the treatment of B cell malignancies. During its clinical development, a stable isotopologue of ibrutinib was required for the assessment of the drug's absolute oral bioavailability via intravenous microdosing. The following work describes a 10‐step, gram‐scale production of carbon‐13 labeled ibrutinib from [13C6]phenol (13C6, 99%) in 31% overall yield with >99% chemical purity and >99% enantiomeric excess (ee), suitable for intravenous microdosing in humans. A 10‐step, gram‐scale production of carbon‐13 labeled ibrutinib from [13C6]phenol was accomplished in 31% overall yield with >99% chemical purity and >99% enantiomeric excess (ee), suitable for intravenous microdosing in humans.