Application background and overview of thiophene[3,2-C]pyridine
Thien[3,2-C]pyridine, thienopyridine compounds are structurally similar to quinoline and isoquinoline. They are a class of heterocyclic compounds with important physiological activity and medicinal value. Currently, there are no Hydrocalcium carbonate has proven that many compounds containing thienopyridine rings have bactericidal, herbicidal and anti-thrombotic activities.
Application and preparation of thiophene[3,2-C]pyridine
1. Preparation of 2,2-dimethyl-N-[(3-thienyl)methyl]ethylamine (1)
Weigh 22.4 g 3-thiophenecarboxaldehyde, 26.6 g aminoacetaldehyde dimethylacetal, 0.2g p-toluenesulfonic acid, 200 mL absolute ethanol, reflux for 3h. Cool to 5°C, add 7.6 g sodium borohydride , reflux for 30 min, distill under reduced pressure, add water to dissolve, extract with ethyl acetate (300 mL×2), combine the organic phases, dry over anhydrous sodium sulfate, and concentrate to obtain yellow oily liquid compound 1.
2.2.2 Synthesis of N-(2,2-dimethoxy)-4-methyl-N-[(3-thienyl)methyl]benzenesulfonamide (2)
Put 35 g of compound 1 and 200 mL of ethyl acetate into a 500 mL round-bottomed flask, add 15.8 g of triethylamine and 30g of p-toluenesulfonyl chloride at 0°C. After dissolving, stir at room temperature for 12 hours. After the reaction, wash with distilled water, 0.1 mol/L hydrochloric acid, and saturated sodium carbonate in sequence, and evaporate the solvent. The resulting viscous oily liquid is separated by column chromatography to obtain white crystal compound 2.
3. Synthesis of thieno[3,2-c]pyridine (3)
Put 10 g of compound 2 and 30 mL of 1,4-dioxane into a 100 mL round-bottomed flask, add 15 mL of concentrated hydrochloric acid, and reflux for 12 h. Cool to room temperature, extract with dichloromethane, and use After neutralizing with sodium bicarbonate, extract with dichloromethane, combine the organic phases, and evaporate the solvent to obtain a brown oily liquid, which is purified by column chromatography to obtain 1.5 g of the yellow crystal compound thiophene[3,2-C]pyridine.
Applications of thiophene[3,2-C]pyridine [1]
Ma Jiaoli and others designed and synthesized a series of thieno[3,2-c]pyridine α-aminophosphonate derivatives using 1H NMR , 13C NMR, 31P NMR and IR were used to characterize it, and preliminary determination of the effect of the above compounds on The tumor suppressor activity of esophageal cancer cells and human liver cancer cells. The synthetic route of the target compound is shown in the figure above. The MTT colorimetric method was used to test the anti-cancer effect of the synthesized target compound. The target compound was prepared into a solution with a concentration of 5 mg/mL using DMSO as the solvent. The solution gradient dilution method was used to set up 3 concentration gradients, respectively: 50, 10, 5 μg/mL, quantitatively determine its anti-tumor effect on esophageal cancer cells (EC109) and human liver cancer cells (HepG2). 5-fluorouracil was used as a positive control drug. The test found that the compound with higher concentration The better the anti-tumor effect, the anti-tumor activity results of 6a ~ 6p at a concentration of 50 μg/mL are shown in Table 1.
The above work uses toluene as the solvent, and synthesizes α-aminophosphonate through a Mannich-like reaction of amine, aldehyde and phosphite in a “one-pot cooking”. TCL tracks the reaction. The imine is first generated from the reaction of amine and aldehyde, and then imine is formed. The reaction between amines and phosphites is simpler and has higher yields. Use 1H NMR, 13C NMR, and 31P NMR in combination , IR and MS were used to characterize the product structure. The tumor suppressor activity of the target compounds was studied. Most of the compounds have the tumor suppressor activity of pinacinate borate. Among them, compounds 6k and 6o inhibited human liver cancer cells by more than 90% higher than their target compounds, and have potential for further research. value, which lays the foundation for continued structural optimization and research on thieno[3,2-c]pyridine-containing α-aminophosphonate derivatives in the future.
