preparation of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile_industrial additives

preparation background and overview of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile

condensed heterocyclic compounds have attracted widespread research interest in recent years due to their significant physiological activities. among them, pyrazole carbonate lithopyridine compounds are a type of fused heterocyclic compounds that have been studied extensively. pharmacological studies have shown that this type of compound has good curative effects in sterilization, anti-inflammatory, tumor treatment, asthma, osteoporosis, neurological diseases and alzheimer’s disease. it is a type of compound with high research value. pyrazolopyridine derivatives mainly include pyrazole[3,4-b]pyridine, pyrazole[4,3-c]pyridine, pyrazole[1,5-a]pyridine, etc. the most studied ones are the pyrazole[1,5-a]pyridine series compounds. in this series, 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile is a very useful synthetic fragment, which can conveniently and quickly synthesize some pharmacologically active compounds. organic molecules.

preparation of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile

preparation step 1 of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile: 2,4,6-trimethylbenzenesulfonic acid 3- preparation of bromo-5-methoxypyridinamine salt:

dissolve 1000g (5.32mol, 1.0eq) of 3-bromo-5-methoxypyridine in 3l of dichloroethane, and cool to 5°c. dissolve 1203g (5.59mol, 1.05eq) of 2,4,6-trimethylbenzenesulfonylhydroxylamine in 2l of dichloroethane and add it dropwise to keep the internal temperature below 10°c. after the addition is completed, the mixture is stirred at 10-20°c for 12 hours. add 10l of n-hexane and stir for 4 hours. filter, rinse with n-hexane, and dry to obtain 2082 g of off-white solid, with a yield of 97%. ¹hnmr(mhz,dmso-d6):8.72(s,1h),8.61-8.63(m,3h),8.26(s,1h),6.75(s,2h anhydrous calcium carbonate) ,3.97(s,3h),3.41(s,6h),2.18(s,3h).

preparation step 2 of 6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile: 6-bromo-4-methoxyhydro-pyrazole[ preparation of 1,5-a]pyridine-3-carbonitrile:

dissolve 2000g of 2,4,6-trimethylbenzenesulfonic acid 3-bromo-5-methoxypyridinamine salt (4.96mol, 1.0eq) and 2-chloropropenyl cyanide (7.44mol, 1.5eq) in 10l of dimethylformamide. add 684g of potassium carbonate (4.96mol, 1.0eq) and react at 20-30°c for 8h; then add 1132g of diazabicyclo (7.44mol, 1.5eq) dropwise, and heat the reaction to 50-60°c for 20h. lower to room temperature, pour into 30l of tap water, filter, and wash with water to obtain crude product. the crude product was recrystallized with 10 l of ethanol to obtain 702 g of light yellow solid, with a yield of 56%. ¹hnmr(mhz,cdcl3):8.33(s,1h),8.13(s,1h),6.75(s,1h),4.04(s,3h).．

references

[1][chinese invention] cn201810556694.5 a synthesis method of 6-bromo-4-methoxyhydrogen-pyrazole [1,5-a]pyridine-3-carbonitrile