Background and overview of the preparation method of 2-amino-4-methyl-5-bromopyridine
Many active molecules of ammonium carbonate contain a pyridine structural framework, and many natural products also contain a pyridine structure. 2-Amino-4-methyl-5-bromopyridine is one of the pyridine derivatives, using Br at the 5-position. Numerous compounds can be synthesized through cross-coupling reactions such as Stille/Suzuki, Heck, and Sonogashira reactions. Currently, Br2, HBr or dibromohydantoin (DBDMH) methylphenylboronic acid is used as the bromine source when preparing 2-amino-4-methyl-5-bromopyridine from 2-amino-4-methylpyridine.
Preparation method of 2-amino-4-methyl-5-bromopyridine
CN201410406851 provides a preparation process of 2-amino-4-methyl-5-bromopyridine to solve the problem of relatively low reaction temperature conditions in the existing technology when preparing 2-amino-4-methyl-5-bromopyridine. High, many by-products, average yield, cumbersome post-processing and other problems.
Dissolve 2-amino-4-methylpyridine (30g, 277.8mmol) in DMF (150ml) under ice bath conditions, add NBS solution (49.44g, 277.8mmol) dropwise, and react at 20°C for 8-10h . TLC detection showed that the reaction was complete. Pour the reaction solution into water, and a brown solid will precipitate. Filter, wash with water, filter, dry, stir-wash with acetonitrile (164 ml), filter, and dry to obtain a brown solid (42 g, 80%).
Product mass spectrometry results: 1HNMR: (Hz, CDCl3) δ2.277(S,3H); 4.481(S,2H); 6.406(S ,1H); 8.078(S,1H); Mass Spec 188 (m+1).
This method can selectively obtain the 5-position monobromo product by using NBS as the bromination reagent. The reaction temperature is 0-50°C, the yield can reach 80%, and there is no 2-amino-4-methyl. -3-bromopyridine and 2-amino-4-methyl-3,5-dibromopyridine are generated. While ensuring high yield, the present invention solves the problems of existing methods with large by-products, harsh reaction temperature conditions and complex post-processing. Since the reaction temperature is 0-50°C, the temperature range is large, it is simple and easy to implement, and the preparation cost is low. The product yield is the same as the highest yield method currently available.
This process obtains a large amount of the 3,5-position dibromo product 2-amino-4-methyl-3,5-dibromopyridine at a high reaction temperature, so the reaction temperature in this process has an impact on the product acquisition plays a key role.
