Hydrochloric Acid → 5-(1-Allyl-1H-imidazol-2-yl)-2-bromo-4-(2,4-dichlorophenyl)-1,3-thiazole

Participants

Reaction Conditions

Reaction Steps

To a solution of N-Allyl-2-bromo-4-(2,4-dichlorophenyl)-1,3-thiazole-5-carboxamide (8.40 g, 21.4 mmol) in dichloromethane (200 mL) was added phosphorus pentachloride (5.05 g, 24.2 mmol) and 4M hydrochloric acid in dioxane (0.833 mL, 3.26 mmol), and the reaction was heated to 60° C. for 90 minutes under an atmosphere on nitrogen. The reaction was allowed to cool to room temperature and then aminoacetaldehyde dimethyl acetal (25.7 mL, 236 mmol) was added slowly through the condenser. The mixture was heated to 60° C. for 2 hours under an atmosphere on nitrogen. The mixture was cooled to room temperature, and water was added (200 mL). The layers were separated and the organic phase was washed with water again (2×200 mL). The organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and washed with dichloromethane (200 mL). To this dichloromethane solution of the intermediate was added 4M hydrochloric acid in dioxane (17 mL, 65 mmol) and the solution was stirred at reflux for 16 hours. The solution was decanted (leaving behind an oily black residue on the flask) and then evaporated and diluted with ethyl acetate and saturated sodium bicarbonate solution. The layers were separated and the aqueous phase was extracted 3 more times with ethyl acetate. The organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography was performed to yield the title compound (5.93 g, 67%). LCMS: (FA) ES+, 416. 1H NMR (400 MHz, d1-chloroform) δ: 7.45-7.42 (m, 1H), 7.25-7.19 (m, 2H), 7.16-7.14 (m, 1H), 6.93-6.90 (m, 1H), 5.55-5.44 (m, 1H), 5.13-5.08 (m, 1H), 5.95-4.88 (m, 1H), 4.19-4.15 (m, 2H).

Provenance & Evidence