Electric Literature of 1093951-76-8,Some common heterocyclic compound, 1093951-76-8, name is 2-Amino-3-bromo-4-fluorobenzonitrile, molecular formula is C7H4BrFN2, 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: 9-Amino-4-X-5-bromo-2-(alkyl)-2,3-dihydropyrrolo[3,4-b]quinolin-1-one (X = H or F).A white slurry of 4-X-3-bromo-2-[1-(alkyl)-5-oxo-2,5-dihydro-1H-pyrrol-3-ylamino]-benzonitrile (1.0 equiv) in t-butanol (0.08-1.00 M) was warmed to 45 C and treated with sodium t-butoxide (1.2 equiv). The resulting green solution was heated at 45 C for 3 h. The reaction was cooled to room temperature, partitioned between methylene chloride and water and the organic layer was washed with saturated aqueous sodium bicarbonate and the combined aqueous layers were extracted with methylene chloride. The organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a light tan solid in greater than 80% yield, which was used without further purification.The intermediate compounds were prepared as follows:4-X-3-Bromo-2-[1-(alkyl)-5-oxo-2,5-dihydro-1H-pyrrol-3-ylamino]-benzonitrile (X = H or F).2-Amino-3-bromo-4-X-benzonitrile (1.0 equiv) and 1-(alkyl)-4-methoxy-1H-pyrrol-2(5H)-one (2.0 equiv) were combined in acetic acid (0.5-0.8 M benzonitrile in HOAc) and heated to 80 C. Methanesulfonic acid (2.5 equiv) was dissolved in acetic acid (10 M) and added dropwise via syringe over 15 min. The reaction was stirred for 1 h at 80 C and then cooled to rt and placed on a rotary evaporator under high vacuum for 15 min at 55 C to remove the acetic acid. The resulting oil was dissolved in methylene chloride and slowly added dropwise over 20 min to a solution of saturated aqueous sodium bicarbonate at 0-5 C, maintaining the pH value above 8. The resultant precipitate from the biphasic system was separated, washed with water twice and then with hexane once, and was dried at 50 C under high-vacuum to give a tan solid as the title compound in 70-85% yield, which was used without further purification (see Table 8).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Amino-3-bromo-4-fluorobenzonitrile, its application will become more common.
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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