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采用密度泛函B3LYP/6-31G(d)方法对奈韦拉平闭环前体2-环丙胺基-N-(2-氯-4-甲基-3-吡啶基)-3-吡啶甲酰胺进行了量子化学研究,并通过闭环前体在强碱的作用下,在有机溶剂中加热回流合成奈韦拉平进行了实验验证。理论计算结果表明,闭环前体分子稳定性较差,具有较强的反应活性;偶极矩与奈韦拉平差别不是很大;与卤素原子相连的碳原子是亲核取代反应的活性中心,仲胺氮原子和羰基氧原子的亲核性存在着竟争。实验结果显示,强碱的用量是影响闭环反应的主要因素,根据理论计算推测的主要产物和副产物,与实验结果相一致。
The nevirapine closed-loop precursor 2-Cyclopropylamino-N- (2-chloro-4-methyl-3-pyridyl) -3-pyridinecarboxamide was subjected to quantum yielding using the B3LYP / 6-31G (d) Chemical research, and through the closed-loop precursor under the action of a strong base, the synthesis of nevirapine by heating reflux in an organic solvent was tested. Theoretical calculations show that the closed-loop precursor has poor stability and strong reactivity; the difference between the dipole moment and nevirapine is not very large; the carbon atom attached to the halogen atom is the active center of the nucleophilic substitution reaction; the secondary amine nitrogen There is a competition for the nucleophilicity of atoms and carbonyl oxygen atoms. The experimental results show that the amount of strong base is the main factor affecting the closed-loop reaction. According to the theoretical calculations, the main products and by-products are in agreement with the experimental results.