Electric Literature of 111721-75-6, These common heterocyclic compound, 111721-75-6, name is 2-Bromo-3-fluoroaniline, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
General procedure: 4-Amino-7-X-8-bromo-N-(alkyl)-cinnoline-3-carboxamide (X = H or F).To a solution of 2-[(3-X-2-bromophenyl)-hydrazono]-N-(alkyl)-2-cyanoacetamide (1.0 equiv) in anhydrous toluene (0.1 M, 1 volume) was added aluminum chloride (3.0 equiv). The reaction was heated with vigorous stirring at 70-90 C for 1-3 h, cooled, and quenched with Rochelle’s salt (saturated aqueous potassium sodium tartrate, 0.5 volume). Afterward, the mixture was stirred at room temperature overnight. The aqueous layer was separated, and the organic layer was treated with fresh Rochelle’ salt (0.5 volume) while stirring at room temperature for 1 h. After separating the resulting layers, the organic suspension was washed with water and filtered to give give a tan solid. Additionally, the organic filtrate was concentrated, and triturated with ether to give a tan precipitate. The resulting solids were filtered to give a tan solid in 30-70% yield of crude product. The combined tan solid was dried at 50 C under high-vacuum to give the title compound, which was used without further purification.The intermediate compounds were prepared as follows:2-[(3-X-2-Bromophenyl)-hydrazono]-N-(alkyl)-2-cyanoacetamide (X = H or F).Solution A: To a mechanically stirred solution of 3-X-2-bromoaniline (1.0 equiv) in acetic acid (2 M, 1 volume) was added water (0.6 volume) at ambient temperature. The mixture was cooled to 0 C, and then concentrated aqueous HCl (0.5 volume) added. A precipitate was formed immediately and the suspension was stirred at 0 C for 20 min. To this suspension was added dropwise a solution of sodium nitrite (1.10 equiv) in water (0.6 volume), maintaining the internal temperature below 5 C. The resulting clear orange solution was stirred at 0 C for another 30 min.Solution B: To a mechanically stirred solution of N-(alkyl)-2-cyanoacetamide (1.25 equiv) in ethanol (4.5 volume) was added a solution of sodium acetate (1.60 equiv) in water (120 volume), and chilled to between 0 C and -5 C.Solution A was poured into solution B, maintaining the internal temperature below 0 C. An orange precipitate was formed gradually. The mixture was stirred below 0 C overnight, and then the orange precipitate was collected by filtration, washed with water (100 mL × 3), and dried at 50 C under high vacuum to remove water. An orange solid was obtained in greater than 95% yield, which was the ‘E’, and used for the next step without further purification.
Statistics shows that 2-Bromo-3-fluoroaniline is playing an increasingly important role. we look forward to future research findings about 111721-75-6.
Reference:
Article; Alhambra, Cristobal; Becker, Chris; Blake, Timothy; Chang, Amy; Damewood Jr., James R.; Daniels, Thalia; Dembofsky, Bruce T.; Gurley, David A.; Hall, James E.; Herzog, Keith J.; Horchler, Carey L.; Ohnmacht, Cyrus J.; Schmiesing, Richard Jon; Dudley, Adam; Ribadeneira, Maria D.; Knappenberger, Katherine S.; MacIag, Carla; Stein, Mark M.; Chopra, Maninder; Liu, Xiaodong F.; Christian, Edward P.; Arriza, Jeffrey L.; Chapdelaine, Marc J.; Bioorganic and Medicinal Chemistry; vol. 19; 9; (2011); p. 2927 – 2938;,
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