Thiophosgene (0.1 mL) was added dropwise to a solution of 1-((4-(5-methylfuran-2-yl)phenyl)amino)cyclobutanecarbonitrile (Intermediate 106, 280 mg, 1.11 mmol) and 5-amino-3-methylpicolinonitrile (Intermediate 2, 177 mg, 1.33 mmol) in DMA (20 mL). The resulting mixture was stirred at 60° C. overnight. MeOH (16 mL) and HCl (2M, 8 mL) were added and the mixture was refluxed for 2 h then cooled to room temperature. The reaction mixture was poured into water (200 mL) and extracted with EtOAc. The organic layer was washed with brine, dried over Sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel (1:3 EtOAc/petroleum ether), to afford 140 mg of 3-methyl-5-(5-(4-(5-methylfuran-2-yl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)picolinonitrile. 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 8.16 (s, 1H), 7.86 (d, 2H), 7.46 (d, 2H), 6.98 (d, 1H), 6.28 (d, 1H), 2.63 (m, 2H), 2.60 (s, 3H), 2.51-2.43 (m, 2H), 2.38 (s, 3H), 1.97 (m, 1H), 1.57 (m, 1H). LCMS [M+1]+ 429.1.
