Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson's disease

The reference standard (4-((5-chloro-4-(methylamino)pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone (HG-10-102-01) and its precursor (4-((5-chloro-4-(methylamino)pyrimidin-2-yl) amino)-3-hydroxyphenyl)(morpholino)methanone (desmethyl-HG-10-102-01) were synthesized from 2,4,5-trichloropyrimide and 3-methoxy-4-nitrobenzoic acid with overall chemical yield 49% in four steps and 14% in five steps, respectively. The target tracer (4-((5-chloro-4-(methylamino)pyrimidin-2-yl) amino)-3-[C-11]methoxyphenyl)(morpholino)methanone ([C-11]HG-10-102-01) was prepared from the precursor desmethyl-HG-10-102-01 with [C-11]CH3OTf through O-[C-11]]methylation and isolated by HPLC combined with SPE in 45-55% radiochemical yield, based on [C-11]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110 GBq/mu mol with a total synthesis time of similar to 40-min from EOB. (C) 2017 Elsevier Ltd. All rights reserved.