CN108912110A - 一种2-氨基恶唑衍生物c26h25o10n3的合成方法 - Google Patents

一种2-氨基恶唑衍生物c26h25o10n3的合成方法 Download PDF

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CN108912110A
CN108912110A CN201811094787.7A CN201811094787A CN108912110A CN 108912110 A CN108912110 A CN 108912110A CN 201811094787 A CN201811094787 A CN 201811094787A CN 108912110 A CN108912110 A CN 108912110A
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amino
carboxylic acid
reaction
compound
chem
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朱海亮
武松宇
叶亚熙
管婧
李章�
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High-Tech Research Institute Nanjing University Lianyungang
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High-Tech Research Institute Nanjing University Lianyungang
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

本发明公开了一种2‑氨基恶唑衍生物C26H25O10N3的合成方法，首先使用化合物1和溴乙酸叔丁酯反应得到羧酸2；然后使用2‑氨基恶唑与羧酸反应得到对应的酰胺，进一步转化为对应的伯胺盐以后和所述羧酸2反应得到2‑氨基恶唑类化合物C26H25O10N3；所述化合物1为2‑(3，4‑双甲氧基苯基)‑5，7‑双羟基‑6‑甲氧基‑4氢‑苯并吡喃‑4‑酮。

Description

一种2-氨基恶唑衍生物C26H25O10N3的合成方法
技术领域
本发明涉及有机化学技术领域，具体涉及一种2-氨基恶唑衍生物C26H25O10N3的制备方法。
背景技术
2-氨基恶唑衍生物C26H25O10N3是重要的生物活性化合物，该类化合物展现出广阔的药理和生理活性，例如使用它们作为吡喃型半乳糖变位酶抑制剂、双阿立新受体抗体和丙肝病毒NS3蛋白酶抑制剂 (E. C. Dykhuizen, J. F. May, A. Tongpenyai, L. L.Kiessling, J. Am. Chem. Soc.2008, 130, 6706-6707; C. D. Cox, M. J. Breslin,D. B. Whitman, J. D. Schreier, G. B. McGaughey, M. J. Bogusky, A. J. Roecker,S. P. Mercer, R. A. Bednar, W. Lemaire, J. G. Bruno, D. R. Reiss, C. M.Harrell, K. L. Murphy, S. L. Garson, S. M. Doran, T. Prueksaritanont, W. B.Anderson, C. Tang, S. Roller, T. D. Cabalu, D. Cui, G. D. Hartman, S. D.Young, K. S. Koblan, C. J. Winrow, J. J. Renger, P. J. Coleman, J. Med.Chem.2010, 53, 5320-5332; T. Zhang, Z. Yan, A. Sromek, B. I. Knapp, T.Scrimale, J. M. Bidlack, J. L. Neumeyer, J. Med. Chem.2011, 54, 1903-1913.）
这类化合物也是许多生物活性分子的重要结构单元 (S. Huang et. al, Bioorg.Med. Chem. Lett., 2008, 18, 2324; Z. Y. Sun et al, Bioorg. Med. Chem. Lett.,2009, 19, 6801.)和重要的有机合成中间体（J. Patman et al, Bioorg. Med. Chem.Lett., 2007, 17, 2540; C. Liu et al, Bioorg. Med. Chem. Lett., 2008, 18,1874）, 这类化合物也例如作为组胺酶H3抑制剂和神经肽抑制剂（I. D. Linney et al,J. Med. Chem., 2000, 43, 2362; U. Z. Y. Sun et al., Bioorg. Med. Chem. Lett.,2009, 19, 6801）。
正由于2-(N-烷基)氨基噻唑和2-(N-烷基)氨基恶唑非常重要，所以发展简单和高效的合成方法来制备这类化合物一直受重视。目前，过渡金属催化环构邻卤苯基脲或多组分浓缩/偶联/环构邻卤苯胺、二氧化硫和氨基烷烃已经被使用，但是这种方法反应生成氢卤酸为副产物，不仅造成严重的环境危害，而且反应的原子效率也低，而且只能合成苯并的2-(N-烷基)氨基噻唑和2-(N-烷基)氨基恶唑衍生物。（L. L. Joyce, G. Evindar, R. A.Batey, Chem. Commun. 2004, 446-447; P. Saha, T. Ramana, N. Purkait, M. A.Ali, R. Paul, T. Punniyamurthy, J. Org. Chem.2009, 74, 8719-8725; Q. Ding, X.He, J. Wu, J. Comb. Chem.2009, 11, 587-591; K. Inamoto, C. Hasegawa, K.Hiroya, T. Doi, Org. Lett.2008, 10, 5147-5150; L. L. Joyce, R. A. Batey, Org.Lett.2009, 11, 2792-2795; D. Ma, X. Lu, L, Shi, H. Zhang, Y. Jiang, X. Liu,Angew. Chem.Int. Ed.2011, 50, 1118-1121.）
过渡金属催化直接的氧化性偶联唑和胺，氯胺和甲酰胺是另一类制备2-(N-烷基)氨基噻唑和2-(N-烷基)氨基恶唑的制备方法，但是这种方法需要使用高负载量的催化剂，多于计量的氧化剂或另外的添加剂，低的官能团兼容性。（D. Monguchi, T. Fujiwara, H.Furukawa, A. Mori, Org. Lett.2009, 11, 1607-1610; J. Y. Kim, S. H. Cho, J.Joseph, S. Chang, Angew. Chem. Int. Ed.2010, 49, 9899-9903; T. Kawano, K.Hirano, T. Satoh, M. Miura, J. Am. Chem. Soc.2010, 132, 6900-6901; S. H. Cho,J. Y. Kim, S. Y. Lee, S. Chang, Angew. Chem.2009, 121, 9291-9294; Angew.Chem. Int. Ed.2009, 48, 9127-9130.）
最近，我们报导了使用铜/碱体系催化2-氨基苯并噻唑和苄醇发生反应生成2-(N-苄基氨基)苯并噻唑衍生物（F. Li, H. Shan, Q. Kang, L. Chen. Chem. Commun.2011. 47,5058-5060）。在原有的体系中，只有苄基伯醇才能发生反应，非苄醇（特别是脂肪族醇、仲醇）不能发生任何反应。此外，氨基唑的类型也局限于2-氨基苯并噻唑。因此，原反应有很大的局限性。
发明内容
本发明提供一种新的2-氨基恶唑衍生物C26H25O10N3合成方法。
本发明采用的方案如下：一种2-氨基恶唑衍生物C26H25O10N3合成方法，其特征在于，首先使用化合物1和溴乙酸叔丁酯反应得到羧酸2；然后使用2-氨基恶唑与羧酸反应得到对应的酰胺，进一步转化为对应的伯胺盐以后和所述羧酸2反应得到2-氨基恶唑类化合物C26H25O10N3；所述化合物1为2-(3，4-双甲氧基苯基)-5，7-双羟基-6-甲氧基-4氢-苯并吡喃-4-酮。
本发明的技术效果如下：同现有技术相比，本发明从商品化或容易合成的2-氨基恶唑伯胺盐出发，通过和醇发生烷基化反应，得到的2-氨基恶唑衍生物C26H25O10N3，反应展现出四个显著的优点：1）使用近于无毒的醇为烷基化试剂；2）反应只生成水为副产物，无环境危害；3）反应原子经济性高；4）相对于原先的铜/碱体系，该反应体系不只局限于苄醇，对于脂肪族醇，仲醇等都展现出高的反应活性。此外，反应体系不只局限于2-氨基苯并噻唑衍生物，而对非苯并的2-氨基恶唑衍生物C26H25O10N3也展现出很高的反应活性，因此，该反应极大的扩展了底物范围，具有广阔的发展前景。
附图说明
图1为2-氨基恶唑路线图。
具体实施方式
下面结合附图对本发明做进一步详细说明。
实施例：一种2-氨基恶唑衍生物C26H25O10N3合成方法，首先使用化合物1和溴乙酸叔丁酯反应得到羧酸2；然后使用2-氨基恶唑与羧酸反应得到对应的酰胺，进一步转化为对应的伯胺盐以后和所述羧酸2反应得到2-氨基恶唑类化合物C26H25O10N3；所述化合物1为2-(3，4-双甲氧基苯基)-5，7-双羟基-6-甲氧基-4氢-苯并吡喃-4-酮。
其核磁数据如下：1H NMR (DMSO, 600 MHz); δ: 19.58(s, 1H, -OH), 11.37(s,1H, -NH-), 9.08 (s, 1H, -OH), 8.21(s, 1H, -NH-), 7.66(d, J =1.6 Hz, 1H, -CH-), 7.32(d, J =3.6 Hz, 1H, -CH-), 7.05(d, J =3.6 Hz, 1H, -CH-), 6.90(d, J =5.9 Hz, 1H, -ArH), 6.84(s, 1H, -ArH), 6.76(s, 1H, -ArH), 6.12(s, 1H, -ArH),4.78 (s, 2H, -CH2-), 3.77~3.73(m, 6H, -CH3), 3.32(t, J =3.6 Hz, 2H, -CH2-),2.51(t, J =3.6 Hz, 2H, -CH2-), 1.86(m, 2H, -CH2-)。

Claims (1)

1.一种2-氨基恶唑衍生物C26H25O10N3的合成方法，其特征在于，首先使用化合物1和溴乙酸叔丁酯反应得到羧酸2；然后使用2-氨基恶唑与羧酸反应得到对应的酰胺，进一步转化为对应的伯胺盐以后和所述羧酸2反应得到2-氨基恶唑类化合物C26H25O10N3；所述化合物1为2-(3，4-双甲氧基苯基)-5，7-双羟基-6-甲氧基-4氢-苯并吡喃-4-酮。
CN201811094787.7A 2018-09-19 2018-09-19 一种2-氨基恶唑衍生物c26h25o10n3的合成方法 Pending CN108912110A (zh)

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Citations (2)

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Publication number Priority date Publication date Assignee Title
WO2001021577A2 (en) * 1999-09-20 2001-03-29 Takeda Chemical Industries, Ltd. Melanin concentrating hormone antagonist
CN101948458A (zh) * 2010-09-07 2011-01-19 中国药科大学 具有抗肿瘤活性的黄芩素衍生物及在医药上的应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001021577A2 (en) * 1999-09-20 2001-03-29 Takeda Chemical Industries, Ltd. Melanin concentrating hormone antagonist
CN101948458A (zh) * 2010-09-07 2011-01-19 中国药科大学 具有抗肿瘤活性的黄芩素衍生物及在医药上的应用

Non-Patent Citations (2)

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