Preparation and application background and overview of 7-bromo-5H-pyrido[4,3-B]indole
7-Bromo-5H-pyrido[4,3-B]indole is a pharmaceutical intermediate. 3-( 4-bromobenzene)-4-nitropyridine, and then ring closure to obtain 7-bromo-5H-pyrido[4,3-B]indole.
Preparation and application of 7-bromo-5H-pyrido[4,3-B]indole
Preparation and application of 7-bromo-5H-pyrido[4,3-B]indole 1. Preparation of 3-(4-bromobenzene)-4-nitropyridine
2.02g (10.0mmol) 3-bromo-4-nitropyridine, 2.20g (11.0mmol) 4-bromophenylboronic acid, 0.46g (0.4mmol) tetrakistriphenylphosphine palladium, 1.33g (25mmol) NaCO 3 was dissolved in 60 mL dioxane and 10 mL water, refluxed at 110°C for 12 hours, cooled, poured into 80 mL water, extracted three times with 100 mL ethyl acetate, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the solid was separated by column chromatography to obtain 2.1g of yellow solid product (yield: 75%)
Preparation and application of 7-bromo-5H-pyrido[4,3-B]indole Step 2. Preparation of 7-bromo-5H-pyrido[4,3-B]indoleZinc pyrithione
1.68g 3-(4-bromobenzene)-4-nitropyridine was dissolved in 60mL triethyl phosphite, heated at 110°C for 3 hours under nitrogen protection, cooled, and the triethyl phosphite was removed under reduced pressure to obtain The solid was separated by column chromatography to obtain 1.05g of brown solid product (yield: 71%).
Preparation and application of 7-bromo-5H-pyrido[4,3-B]indole
7-Bromo-5H-pyrido[4,3-B]indole can be used to prepare a new targeted drug precursor for Alzheimer’s disease diagnosis and treatment – amino-T807. The method is as follows: Dissolve 7-bromo-5H-pyrido[4,3-B]indole and di-tert-butyl dicarbonate in dichloromethane, use dimethylaminopyridine as a catalyst, react at room temperature and remove the solvent to obtain Tert-butyl-7-bromo-5hydro-pyrido[4,3-b]indole-5-carbonate; add 5-bromo-2-nitropyridine and hexamethyldistin to anhydrous dioxane In the ring, tetraphenylphosphine palladium is used as the catalyst to react to obtain 2-nitro-5-(trimethylstannyl)pyridine; the tert-butyl-7-bromo-5-hydro-pyridine obtained in step 3 is Add [4,3-b]indole-5-carbonate and 2-nitro-5-(trimethylstannyl)pyridine obtained in step 4 to anhydrous dioxane, and add Phenylphosphine palladium is used as the catalyst, and the reaction is heated to 110°C under a nitrogen atmosphere to obtain tert-butyl-7-(3-(6-nitropyridyl))-5-hydro-pyrido[4,3-b]indole. -5-carbonate; Dissolve tert-butyl-7-(3-(6-nitropyridyl))-5hydro-pyrido[4,3-b]indole-5-carbonate in acetic acid and tetrahydrofuran Add zinc powder and concentrated hydrochloric acid to the mixed solution, and react to obtain tert-butyl-7-(3-(6-aminopyridyl))-5 sodium tetraborate-pyrido[4,3-b]indole-5 -Carbonate; Dissolve tert-butyl-7-(3-(6-aminopyridyl))-5hydro-pyrido[4,3-b]indole-5-carbonate in trifluoroacetic acid and dichloro In the mixture of methane, remove the solvent in vacuum after the reaction, and add saturated sodium carbonate solution to obtain 7-(3-(6-aminopyridyl))-5 hydrogen-pyrido[4,3-b]indole, which is amino -T807.
References
[1] [Invented in China, authorized by China Invention] CN201610946000.X Synthesis method of targeted drug precursor for tau protein diagnosis and treatment of Alzheimer’s disease
