Synthesis Of 2-substituted-6,7-diazaindoles Derivatives

The diazaindoles derivatives are the most important heterocycle compounds and intermediates for the synthesis of many biologically active compounds. In the thesis, we have developed an efficient synthesis of 2-substituted-5-chloro-6, 7-diazaindoles through cross- coupling and heteronnulation of 6-chloro-4-bromo-3-aminopyridazines and aryl-, or alkylalkynes. The 6-chloro-4-bromo-3-amino pyridazines and terminal alkynes are also synthesized 1. The synthesis of raw materials6-Chloro-4-bromo-3-aminopyridazines was prepared using 3, 6-dichlor pyridazines as starting materials.(Hetero)aryl acetylene were obtained via Sonogashira coupling reaction of aryl halides with trimethylsilyl-acetylene or 2-methyl-3-butyn-2-ol followed by deprotection reaction. 2. 2-Substituted-5-chloro-6,7-diazaindolesThe model reaction of 6-chloro-4-bromo-3-aminopyridazines and phenylacetylene was investigated to get the optimum condition of the Sonogashira reaction and intramolecular cyclization reaction. The optimum condition is that the reaction catalyst system with Pd(OAc)2 as the catalyst, PPh3 as ligand, propylamine as base, Cu I as additive, DMF as solvent, 40℃ for 4h, after addition of Na H, the reaction was kept for 1 more hour. Upon the optimum reaction condition, 27 2-Substituted-5-chloro-6,7-diazaindoles were synthesized. All the desired products were characterized by 1H NMR 13 C NMR and HRMS.