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·780· 精细化工 FINE CHEMICALS 第 36 卷

如表 4 所示，过量的甲酰胺有利于偶联反应的 positive non-small-cell lung cancer (ARCHER 1050): a randomised,
进行，目标产物收率显著提高（No.1~4）；当甲酰胺 open-label, phase 3 trial[J]. Lancet Oncology, 2017, 18(11):
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用量增加为 BA 的 2 倍后，目标产物收率增加不明 [3] Huang Ziling (黄子凌), Huang Lanshan (黄兰姗), Shen Siqiao (沈思
显（No.3~4）。在 CuI/4-羟基-L-脯氨酸的作用下， 乔), et al. The influence on cell proliferation and apoptosis of
combined afatinib with Mithramycin A in human hepatocellular
偶联和环化反应在较低温度下即可进行，但目标产
carcinoma cell line HepG2[J]. ACTA Universitatis Medicinalis
物收率较低（No.5~6）；当反应温度升高至 80 ℃时， Nanjing (Natural Science) (南京医科大学学报: 自然科学版),
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[4] Wang Shengqi (王胜奇). The reversal effect of afatinib on ABCB1-
标产物收率有所下降（No.7）。在微波促进下，偶联
mediated multidruf resistance in human ovarian cancer and its
和环化反应 10 min 即可较好地完成；延长反应时间， mechanisms[D]. Guangzhou: Southern Medical University Guangzhou
目标产物收率反而降低（No.9~10）。 (南方医科大学), 2016.
[5] Zhao Ying (赵颖), Chi Jiangrui (迟江瑞), Zhao Hongmeng (赵洪猛),
综上所述，合成 QA 的优化反应条件为：BA
et al. Effect of afatinib on the proliferation and apoptosis of human
5 mmol，甲酰胺 10 mmol，CuI 用量 10%，4-羟基-L- breast cell lines and its mechanisms[J]. Chinese Journal of Clinical
脯氨酸用量 10%，碳酸钾 10 mmol，DMF 10 mL，微 Oncology (中国肿瘤临床), 2017, 44(15): 739-743.
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QA 的收率为 96.4%。 [J]. Journal of Cranio-Maxillofacial Surgery, 2018, 46(3): 492-497.
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single-agent pan-human epidermal growth factor receptor (HER)
波促进下，与 3-氯-4-氟苯胺发生加成反应得到中 inhibitor dacomitinib in locally advanced unresectable or metastatic
间产物 BA，收率 93.8%，得到的优化反应条件为： skin squamous cell cancer[J]. European Journal of Cancer, 2018, 97:
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2-溴-4-氟-5-硝基苯甲腈 10 mmol，3-氯-4-氟苯胺
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[10] Cheng Haibo (程海博), Xu Bin (徐斌), Zhang Huibin (张惠斌), et
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