2,3-二甲基-6-氨基-2H-吲唑的合成研究

A Study on the Synthesis of 2,3-diethyl-6-nitro-2H-indazole

目的:设计与合成具有分子靶向性、低毒高效新型血管生成抑制剂类抗肿瘤药物中间体。方法:以2-乙基苯胺为原料经醋酐酰化、浓硝酸低温硝化及去酰基保护合成2-乙基-5-硝基苯胺,后用亚硝酸钠关环得3-甲基-6-硝基-1H-吲唑,经硫酸二甲酯甲基化得2,3-二甲基-6-硝基-2H-吲唑,最后用氯化亚锡将其还原得到目标产物,通过1HNMR确定结构与目标产物一致。结果:所用的合成方法可靠,质量可控,总收率为15.7%。结论:所采用合成方法能用于2,3-二甲基-6-氨基-2H-吲唑的制备。

Objective： To design and synthesize a key intermediate of novel molecule-targeting angiogenesis inhibitor with potent anti-tumor activity and low toxicity. Methods： 2-ethyl aniline was used as starting material of the synthesis and was processed by acetic anhydride acylation, strong nitric acid hitraction at low temperature, and desacyl synthesis to produce 2-ethyl-5-nitro aniline. The product was then synthesized to 3-methyl-6-nitro-1H-indazole by using ring-closing reaction in the presence of NaNO2, and then ethylated to obtain 2,3-diethyl-6- nitro-2H-indazole. The latter compound was then reduced by SnCl2/Hcl to get target compound 2,3-diethyl-6-nitro-2H-indazole. Result： The obtained compound was identified as the target one by ^1H NMR. Conclusion： The route was suitable for the preparation of 2,3 -diethyl-6-nitro-2 H -indazole.