Step 1: Synthesis of ethyl 2-amino-4-trifluoromethylthiazole-5-carboxylate (A-31)
To an ethanol (200 mL) suspension of thiourea (3.3 g, 22.88 mmol) was added ethyl 2-chloro-4,4,4-trifluoroacetoacetate (5 g, 22.88 mmol), and the resulting reaction mixture was heated at 80 °C for 24 hours. Subsequently, the reaction mixture was cooled to room temperature and concentrated under vacuum. The crude product was purified by column chromatography to afford ethyl 2-amino-4-trifluoromethylthiazole-5-carboxylate (A-31) as a colorless oil (5.98 g, 85% yield).
1H NMR (500 MHz, CDCl3) δ 4.32 (q, 2H, J = 7.0 Hz), 3.56 (m, 4H), 1.70 (m, 6H), 1.36 (t, 3H, J = 7.0 Hz); LCMS (ESI) [M + 1]+ 309.3.
