application prospect | 5-amino -1-methyl -1H-indazole is an important pharmaceutical intermediate, which is used to construct the nucleus of active drugs and has broad application prospects in the synthesis and screening of small molecule chemical drugs. Active drug molecules containing indazole ring structure, as potential protein kinase inhibitors, have important application prospects in the treatment of cancer, cardiovascular disease, heart disease, immunodeficiency, glaucoma, diabetes, inflammation and other fields. |
preparation | using 2-amino -5-nitrotoluene as raw material, 5-amino -1-methyl -1H-indazole is obtained through ring closure, methylation and reduction reactions. The preparation reaction formula is as follows: 5-amino -1-methyl -1H-indazole preparation reaction formula 55g 2-amino -5-nitrotoluene is dissolved in 2.5L glacial acetic acid, cooled, 25g sodium nitrite and 60ml water are added to the solution, and the reaction temperature does not exceed 25 ℃. The generated yellow precipitate is filtered out, the reaction solution is placed for 3 days and then concentrated under reduced pressure. The residue is stirred into paste with 200ml of water, filtered, the filter cake is washed with cold water, dried, and recrystallized with methanol to obtain 42-47g of 5-nitroindazole with a yield of 72%-80%. Add N,N-dimethylformamide solution and 5-nitroindazole into the three-port reaction bottle, stir for 30 minutes, slowly add methyl iodide at 0 ℃, add methylene iodide after dropping, and heat up to room temperature for reaction. Thin layer chromatography to detect the progress of the reaction, after the reaction is complete, ethyl acetate is added, washed 3 to 4 times, the organic phase is dried with anhydrous magnesium sulfate, filtered, concentrated to obtain the product 5-nitro-1-methyl-1H-indazole. 5-nitro -1-methyl -1H-indazole and methanol were added to a 2L single-mouth bottle, stirred and dissolved, Pd/C(10g,Pd: C = 10: 1) was added, and hydrogen was introduced after air was removed. Stir at room temperature for 4 hours, and the reaction is complete. Pd/C is removed by suction filtration, the filtrate is evaporated to remove the solvent to obtain a solid crude product, which is dissolved in 500mL of ethyl acetate, washed with 200mL of water, the organic phase is dried with anhydrous sodium sulfate, the filtrate is evaporated to remove the solvent, the residue is beaten with n-hexane, and the target compound 5-amino -1-methyl -1H-indazole is dried. |