Efficient synthesis of [11C]H-1152, a PET probe specific for Rho-kinases, highly potential targets in diagnostic medicine and drug development

A novel PET probe, [11C]H-1152, specific for Rho-kinases, was synthesized efficiently for the first time based on rapid Pd0-mediated C-[11C]methylation using [11C]methyl iodide and a tributylstannyl precursor, giving the isolated radioactivity of 3.8±1.2 GBq (n=3), specific radioactivity of 97±10 GBq μmol−1 (n=3), and high chemical and radiochemical purities (>99%). The decay-corrected radiochemical yield based on 11CH3I was 63±14%. New potentials of a trifluoroacetyl (TFA) group as a tolerant protecting and facile deprotecting group of a secondary amine were demonstrated by highly selective stannylation (via lithiation of isoquinoline moiety using t-C4H9Li) and ready removal by hydroxide ion leaving the arylstannyl moiety intact, respectively. The role of excess hexamethylphosphoric triamide (HMPA) to realize an efficient stannylation of the isoquinoline lithium species is also discussed briefly. [Display omitted]