A glass microwave reaction vessel was charged with 1-(trans-3-aminocyclobutyl)-5-bromo-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 82, 0.143 g, 0.397 mmol) and 2-chloro-7-fluoroquinazoline (0.118 g, 0.646 mmol). DMSO (2 mL) was added followed by N,N-diisopropylethylamine (0.300 mL, 1.725 mmol) and the reaction mixture was sealed under argon and heated at 100° C. overnight. The reaction was cooled room temperature and diluted with water. The precipitate was filtered to give an off-white solid. The material was dissolved in 4M HCl in dioxane and purified by reverse-phase HPLC (Gilson; Gemini-NX 10 m C18 110A AXIA, 100×50 mm column) eluting with 0.1% TFA-H2O:0.1% TFA CH3CN (9:1→1:9). The fractions containing the desired product were combined and concentrated in vacuo. The residue was dissolved in MeOH and loaded onto an Si-Carbonate (Silicycle) cartridge eluting with DCM/MeOH to give 50 mg (27%) of a white crystalline solid. ESI MS 469.9, 471.8 [M+1].
