(S)-1-乙基-2-氨甲基吡咯烷和2,4-二氨基-6-溴甲基蝶啶的合成-毕业论文（可编辑）.docVIP

摘 要 第一章:S-1-乙基-2-氨甲基吡咯烷是一种重要的手性药物中间体,常用于 生产抗精神病药物左旋舒必利、舒托必利及其他药物,因此该化合物的合成具有 很高的实用价值。 本章以 L-脯氨酸为原料,设计了 4条路线合成S-1-乙基-2-氨甲基吡咯烷。 经 N,O-双乙基化、氨解、还原三步反应合成目标化合物,反应路径短、操作简 单、经济安全。由于氨解反应进行较慢,本章中通过改变氨解试剂、加入催化剂、 加热等手段,提高了氨解反应速率,缩短了反应时间。S-1-乙基吡咯烷-2-甲酰 胺属于伯酰胺,为了将其还原为S-1-乙基-2-氨甲基吡咯烷,文中尝试了不同的 还原体系,发现使用 KBH -BF ?Et O体系还原,成本低、收率较高,是一种还原 4 3 2 的好方法。经该方法合成S-1-乙基-2-氨甲基吡咯烷,三步反应的总收率为 68.6%,反应路径短、成本低、收率较高,适用于工业化生产。 第二章:2,4-二氨基-6-溴甲基蝶啶是合成抗肿瘤药物的重要中间体。由 2,4- 二氨基-6-溴甲基蝶啶合成的抗肿瘤药物甲氨蝶呤及其衍生物,收率高、纯度好。 因此该化合物的合成研究具有重要的实用价值。 目前,文献已有的 2,4-二氨基-6-溴甲基蝶啶的合成方法存在收率低、所用原 料不易得等缺点。本章以 2,4,5,6-四氨基嘧啶盐酸盐和 1,3-二羟基丙酮环合生成 2,4-二氨基-6-羟甲基蝶啶,再经溴代生成 2,4-二氨基-6-溴甲基蝶啶,最后对该合 成路线进行了进一步的优化,两步反应的总收率为 38.4%。该合成方法操作简单、 所用原料简单易得、成本低,是工业上合成 2,4-二氨基-6-溴甲基蝶啶的好方法。关键词:S-1-乙基-2-氨甲基吡咯烷 氨解 还原 2,4-二氨基-6-溴甲基蝶啶 ABSTRACT Part 1: S-2-Aminomethyl-1-ethylpyrrolidine is an important chiral pharmaceutical intermediate and widely used in the synthesis of antipsychotic drugs of L-sulpiride, sultopride, etc. Consequently, the synthesis of S-2-aminomethyl-1-ethylpyrrolidine is valuableIn this paper, we developed a method to prepare S-2-aminomethyl- 1-ethylpyrrolidine using L-proline as the starting material through N,O-diethylation, ammonolysis, and reduction steps. In order to increase the rate of ammonolysis and reduce the reaction time, the ammonolysis reagent was changed, the catalyst was added and the reaction temperature was increased. In the reduction of S-1-ethyl-2-pyrrolidinecarboxamide, several reduction systems have been tried and we found that KBH -BF ?Et O was the better one. It owns the advantages of low cost, 4 3 2 high yield, and safe operationAll the reactants are easy to obtain and economically inexpensive. This method has the advantages of low cost, high yield total yield: 68.6%, simple and safe operation. This mehod is suitable for chemical industry production Part 2: 2,4-Diamino-6-bromomethylpteridine is an important intermediate for the synthesis of methotrexate and its derivatives