1. 毕业设计（论文）的内容和要求

课题的基本要求：（1）通过查阅文献，了解该课题的国内外研究现状；（2）学习和掌握有关计算软件的使用；（3）重复文献报道的合成路线，从最终的实验结果中选取其中最优的路线，进行反应条件的系统筛选，并从大量实验数据中确认最优的反应条件，在确认反应条件的基础上，对反应的后处理易操作性以及合理性上做出调整，并最终初步确认该化合物的合成工艺；（4）分析结果，撰写毕业论文。

预定完成任务及时间：2016年6月11日

2. 参考文献

[1] Preparation of biaryls, arylheteroaryls, heteroaryls, biarylacetylenes and related compounds end-capped with aminoacid or peptide derivatives as antiviral agents Assignee: Gilead Sciences, Inc., USA; Kim, Choung, U[P].Accession Number: 2010:1433172, CAN 153:643864, CAPLUS [2] Preparation of quinoline derivatives and analogs for use in the treatment of hepatitis C virus infection in combination with ribavirin By: Delaney, William E., IV; Lee, William A.; Oldach, David W.; Rousseau, Franck[P]Patent Information: Dec 15, 2011, WO 2011156757, A1 Priority: Jun 10, 2010, US 2010-61353460 [3] Preparation of substituted nucleotide phosphorothioate analogs for treating viral infections, cancer, and/or parasitic diseases By: Smith, David Bernard; Deval, Jerome; Dyatkina, Natalia; Beigelman, Leonid; Wang, Guangyi [P]Accession Number: 2012:426940, CAN 156:450612, CAPLUS [4] Preparation of pyridazinylmethylimidazopyridine derivatives and analogs for use in the treatment of hepatitis C virus using combination chemotherapy By: Delaney, William E.; Link, John O.; Mo, Hongmei; Oldach, David W.; Ray, Adrian S.; Watkins, William J.; Yang, Cheng Yong; Zhong, Weidong [P] Source: PCT Int. Appl., 143pp., Patent, 2012, CODEN: PIXXD2 Accession Number: 2012:925592, CAN 157:165566, CAPLUS [5] Synthesis imidazolyl amino acid derivatives as potential antiviral agents By: Scott, Robert William; Vitale, Justin Philip; Matthews, Kenneth Stanley; Teresk, Martin Gerald; Formella, Alexandra; Evans, Jared Wayne Assignee: Gilead Sciences, Inc., USA [P] Patent Information: Dec 05, 2013, US 20130324740, A1 [6] Preparation of solid forms of antiviral ledipasvir [P] By: Scott, Robert William; Wang, Fang; Shi, Bing; Mogalian, Erik Patent Information: Dec 05, 2013, US 20130324496, A1 [7] Preparation of solid forms of antiviral ledipasvir [P] By: Scott, Robert William; Wang, Fang; Shi, Bing; Mogalian, Erik Patent Information: Dec 12, 2013, WO 2013184698, A1 [8] Preparation of pyridazinylmethylimidazopyridine derivatives and analogs for use in the treatment of hepatitis C virus using combination chemotherapy [P] By: Ray, Adrian S.; Watkins, William J.; Link, John O.; Oldach, David W.; Delaney, William E., IV Patent Information: Mar 21, 2013, WO 2013040492, A2 [9] Preparation of linked bis-1H-imidazoles, bis-1H-benzimidazoles and analogs end-capped with amino acid or peptide derivatives as NS5A synergists and their anti-HCV synergist combinations with an NS5A-targeting compound [P] By: Hewawasam, Piyasena; Kadow, John F.; Lopez, Omar D.; Meanwell, Nicholas A.; Tu, Yong; Wang, Alan Xiangdong; Xu, Ningning; Belema, Makonen; Fridell, Robert A.; Gao, Min; Lemm, Julie A.; O'Boyle, Donald R., II; Sun, Jin-Hua; Wang, Chunfu; Wang, Ying-Kai; Gupta, Samayamunthula Venkata Satya Arun Kumar; Srinivasu, Pothukanuri; Kumar, Indasi Gopi; Kumar, Ponugupati Suresh Patent Information: Jul 18, 2013, WO 2013106520, A1 [10] Preparation of linked bis-1H-imidazoles, bis-1H-benzimidazoles and analogs end-capped with amino acid or peptide derivatives as NS5A synergists and their anti-HCV synergist combinations with an NS5A-targeting compound [P] By: Hewawasam, Piyasena; Kadow, John F.; Lopez, Omar D.; Meanwell, Nicholas A.; Tu, Yong; Wang, Alan Xiangdong; Xu, Ningning; Gupta, Samayamunthula Venkata Satya Arun Kumar; Srinivasu, Pothukanuri; Kumar, Indasi Gopi; Kumar, Ponugupati Suresh; Belema, Makonen; Fridell, Robert A.; Gao, Min; Lemm, Julie A.; O'Boyle, Donald R., II; Sun, Jin-Hua; Wang, Chunfu; Wang, Ying-Kai Patent Information: Jul 18, 2013, US 20130183269, A1 [11] Synthesis method of precursor compound for synthesizing intermediate of GS5885 [P] By: Liu, Rucheng; Peng, Shaoping Patent Information: Nov 12, 2014, CN 104140417, A [12] Discovery of Ledipasvir (GS-5885): A Potent, Once-Daily Oral NS5A Inhibitor for the Treatment of Hepatitis C Virus Infection [J] By: Link, John O.; Taylor, James G.; Xu, Lianhong; Mitchell, Michael; Guo, Hongyan; Liu, Hongtao; Kato, Darryl; Kirschberg, Thorsten; Sun, Jianyu; Squires, Neil; Parrish, Jay; Keller, Terry; Yang, Zheng-Yu; Yang, Chris; Matles, Mike; Wang, Yujin; Wang, Kelly; Cheng, Guofeng; Tian, Yang; Mogalian, Erik; Mondou, Elsa; Cornpropst, Melanie; Perry, Jason; Desai, Manoj C. Source: Journal of Medicinal Chemistry, Volume: 57, Issue: 5, Pages: 2033-2046, Journal; Online Computer File, 2014, CODEN: JMCMAR, ISSN: 0022-2623, DOI: 10.1021/jm401499g [13] Combination formulation of ledipasvir and sofosbuvir antiviral agents[P] By: Chal, Ben; Mogalian, Erik; Oliyai, Reza; Pakdaman, Rowchanak; Stefanidis, Dimitrios; Zia, Vahid Patent Information: Jul 31, 2014, US 20140212491, A1 [14]Process for preparation of ledipasvir and intermediates thereof [P] By: Huang, Chengjun; Fu, Gang; Fu, Shaojun; Wei, Zhewen; Li, Wei; Zhang, Xixuan Patent Information: Aug 12, 2015, CN 104829599, A [15] Process for preparation of fluorenylethanone derivatives as Ledipasvir intermediates [P] By: Zhang, Xixuan; Fu, Shaojun; Wei, Zhewen; Li, Wei; Huang, Chengjun Patent Information: Apr 15, 2015, CN 104513223, A

3. 毕业设计（论文）进程安排

2016-02-25~2016-03-25 系统地检索和阅读相关中外文文献，了解该课题的国内外研究现状。

对该化合物目前所拥有的合成路线有大致了解，并对之后的工艺优化做出系统的设计，完成开题报告。

2016-03-25~2016-05-10 首先重复文献报道的合成路线，从最终的实验结果中选取其中最优的路线，进行反应条件的系统筛选，并从大量实验数据中确认最优的反应条件，在确认反应条件的基础上，对反应的后处理易操作性以及合理性上做出调整，并最终初步确认该化合物的合成工艺。