Scheme 3

Synthesis of [¹¹C]EAI045 precursor (3a): (i) trimethylsilyl cyanide, ammonia in methanol, 45 °C, 30 min; (ii) hydrochloric acid in water, reflux/room temperature, overnight; (iii) di-tert-butyl dicarbonate, sodium hydroxide, water/tert-butanol, room temperature, overnight, 5% yield over three steps; (iv) N,N-diisopropylethylamine, propylphosphonic anhydride, ethyl acetate/dimethylformamide, room temperature, overnight, 15% yield; (v) trifluoroacetic acid, dichloromethane, room temperature, 15 min; (vi) 1,8-diazabicyclo(5.4.0)undec-7-ene, sodium sulfate, methanol, 55 °C, 1 h, Sodium cyanoborohydride, 55°C, 1h, 9% yield