Syntheses Of Indole-Benzimidazole Derivatives

Tumor is one of the diseases which causes serious damage to human health. The formation of tumor cells needs new blood vessels to provide nutrition and excrete metabolites. VEGF is one of the important factors to stimulate angiogenesis. VEGFR-2 is a kind of main VEGF receptors. Studies have shown that blocking the interaction of VEGF and VEGFR-2 tyrosine kinase can inhibit the growth of tumor cells, and achieve the effect of treatment in tumor. So VEGFR-2 tyrosine kinases as a target of tumor treatment is one of the main directions of the present studies. Indole-benzimidazole derivatives are a class of VEGFR-2 tyrosine kinase inhibitors using the method of computer aided drug design. This article mainly explored the syntheses of indole-benzimidazole derivatives. The following three aspects are the main points:1.Using the method of L-B indole synthesis, substituted 2-nitrotoluene reacted with DMFDMA in DMF, and then produced 4-nitroindole、6-nitroindole、7-methylindole under the reduction of reductant. Through the protection of the N and third of indole circle,5-bromine indole and 5-nitroindole were synthesized. Using Vilsmeier reaction, substituted indole reacted with POCl3 and DMF, and produced six substituted indole-3-carboxaldehyde. The substituted indole reacted with trifluoroacetic anhydride, and produced six substituted indole-3- carboxylic acid.2. O-phenylendiamine as the raw material reacted with cyanamide under acid condition, and then produced 2-aminobenzimidazole.2-aminomethyl benzimidazole was synthesized by o-phenylendiamine and glycine under the catalysis of phosphoric acid and phosphoric acid. Aniline and aniline derivatives reacted with ammonium thiocyanate and bromine to produce 2-aminobenzothiazole and 2-aminobenzothiazole derivatives.3.2-(1H-indole-3-yl)-1H-benzimidazole was synthesized from indole-3-carboxaldehyde and o-phenylendiamine under the oxidation of oxygen in the air in methanol. Indole-3-carboxylic acid reacted with thionyl chloride to produce indole-3-carboxylic chloride, which was reacted with 2-aminobenzimidazole-.2-aminobenzothiazole,2-Amino-6-methoxybenzothiazole to produce N-(1H-benzimidazole-2-yl)-1H-indole-3-carbamoyl、N-(benzothiazole-2-yl)-1H-indole-3-carbamoyl、N-(6-methoxybenzothiazole-2-yl)-1H-indole-3-carbamoyl.N-((1H-indole-3-yl)methyl)-2-amino-1H-benzimidazole、N-((1H-indole-3-yl)methyl)-2-aminobenzothiazole was synthesized from indole-3-carboxaldehyde and 2-aminobenzimidazole、2-aminobenzothiazole through the reductive amination reaction.