Reference of 916176-52-8 , The common heterocyclic compound, 916176-52-8, name is 4-Bromo-5-chloro-1H-pyrrolo[2,3-b]pyridine, molecular formula is C7H4BrClN2, 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.
As shown in Scheme 11, mCPBA (4.75 g) was added to a solution of 5-chloro-1H-pyrrolo[2,3-b]pyridine (3.00 g) in ethyl acetate (20 mL) at 0 C. The reaction mixture was stirred at room temperature for 12 hours and the solvents removed in vacuo to leave a residue, to which aqueous 30% potassium carbonate was added. Extraction with 10% MeOH/DCM (5¡Á) and evaporation gave the crude N-oxide, which was used directly in the next reaction.To the N-oxide in DMF at 0 C. (10 mL) was added tetramethyl ammonium bromide (1.00 g) and methylsulfonyl anhydride (1.5 g). The reaction mixture was stirred at 0 C. for 30 minutes and brought to room temperature over 2 hours. Water (40 mL) was added, followed by extraction with dichloromethane (3¡Á) and concentration of the combined organics in vacuo. Silica gel chromatography (0 to 40% EtOAc/DCM) gave 4-bromo-5-chloro-1H-pyrrolo[2,3-b]pyridine, which was contaminated with the corresponding 3-bromo and 3,4-dibromo compounds.To the mixture of the bromides (0.128 g) in 1,4-dioxane (4 mL) was added 2-acetamidophenylboronic acid (0.20 g), PdCl2dppf2 (0.04 mg) and potassium phosphate (0.47 g). The reaction mixture was heated at 90 C. overnight. The reaction mixture was cooled and water (20 mL) was added. Extraction with dichloromethane (3¡Á) and concentration of the combined organic extracts gave a mixture of 3- and 4-regional isomers, which were separated by silica gel chromatography (0 to 100% EtOAc/hexane) to produce the 4-isomer (compound 1008, 26 mg) as a pure compound. Compound 1008 was refluxed in concentrated hydrochloric acid for 50 min. Concentration of the reaction mixture in vacuo gave compound 1009.Compound 1009 (6 mg) was mixed with the 2,6-difluorobenzaldehyde (20 mg) in methanol and 4N HCl-dioxane (0.1 mL). The resulting solution was heated at 95 C. and the progress of the reaction was monitored by LC-MS. When the reaction was judged to be complete, the mixture was concentrated in vacuo and ether was added. Compound 52 was isolated as the HCl salt.
The synthetic route of 916176-52-8 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Vertex Pharmaceuticals Incorporated; US2010/81645; (2010); A1;,
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