CN107987067A - 一类新型的5-酰胺基-1,4,5-三取代的1,2,3-三氮唑 - Google Patents

一类新型的5-酰胺基-1,4,5-三取代的1,2,3-三氮唑 Download PDF

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CN107987067A
CN107987067A CN201711084614.2A CN201711084614A CN107987067A CN 107987067 A CN107987067 A CN 107987067A CN 201711084614 A CN201711084614 A CN 201711084614A CN 107987067 A CN107987067 A CN 107987067A
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triazoles
amide groups
nmr
trisubstituted
cdcl
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宋汪泽
郑楠
郑玉斌
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Dalian University of Technology
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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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles

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Abstract

本发明属于有机合成技术领域，一类新型的5‑酰胺基‑1,4,5‑三取代的1,2,3‑三氮唑，其化学结构式如下：其中，R1和R2为氢原子、烷基、烷氧基或芳基，R1和R2相同或不同；R3为烷基、烷氧基或芳基；R4为烷基或芳基。本发明的有益效果：本发明中5‑酰胺基‑1,4,5‑三取代的1,2,3‑三氮唑类化合物具有潜在的生理活性。

Description

一类新型的5-酰胺基-1,4,5-三取代的1,2,3-三氮唑
技术领域
本发明属于有机合成技术领域，涉及一种新型的5-酰胺基-1,4,5-三取代的1,2,3-三氮唑的结构。
背景技术
5-酰胺基-1,4,5-三取代的1,2,3-三氮唑是一类重要的杂环化合物，有潜在的生物活性和成药的可能性。近年来，已有一系列文献或专利报道了5-酰胺基-1,2,3-三氮唑的具良好的生物活性。
2012年，Budd课题组筛选了一系列化合物，最后发现一类具有5-酰胺基-1,2,3-三氮唑结构的化合物对溶血磷脂酸受体-1(LPA1)有很强的拮抗作用。(J.Med.Chem.2012,55,7920)。2015年Taddei课题组报道了一类5-酰胺基-1,2,3-三氮唑对热休克蛋白90(HSP90)有良好的抑制作用(J.Org.Chem.,2015,80,2562)。随后该类化合物受到广泛研究与关注。由于其在化学及生物学领域的优异表现，因此保护其结构具有重要的意义。
发明内容
本发明要解决的技术问题是保护一类具有5-酰胺基-1,4,5-三取代的1,2,3-三氮唑核心结构的化合物。其具有潜在的生理活性和药用价值，本专利将保护这一类化合物的结构。
本发明的技术方案：
一类新型的5-酰胺基-1,4,5-三取代的1,2,3-三氮唑，其化学结构式如下：
其中，R1和R2为氢原子、烷基、烷氧基或芳基，R1和R2相同或不同；
R3为烷基、烷氧基或芳基；
R4为烷基或芳基。
本发明的有益效果：本发明中5-酰胺基-1,4,5-三取代的1,2,3-三氮唑类化合物具有潜在的生理活性。
具体实施方式
以下结合技术方案，进一步说明本发明的具体实施方式。
实施例1：1-苄基-4-苯基-5-(吡唑啉2-酮基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ7.69(d,J＝5.0Hz,2H),7.36-7.34(m,6H),7.29(d,J＝10.0Hz,2H),5.60(s,2H),4.14(t,J＝10.0Hz,2H),2.96(br s,2H).13C NMR(125MHz,CDCl3):δ156.6,141.9,134.4,129.4,129.3,129.1,128.9,128.8,127.9,126.3,63.3,53.1,44.5.HRMS(ESI)m/z calcd for C18H16N4O2(M+Na)+343.1171,found 343.1172.
实施例2：1-苄基-4-对甲氧基苯基-5-(吡唑啉2-酮基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ7.53(d,J＝10.0Hz,2H),7.31-7.27(m,3H),7.21(d,J＝10.0Hz,2H),6.87(d,J＝10.0Hz,2H),5.50(s,2H),4.06(t,J＝10.0Hz,2H),3.73(s,3H),2.86(br s,2H).13C NMR(125MHz,CDCl3):δ160.0,155.7,141.9,134.5,129.2,128.9,127.9,127.7,127.2,121.9,114.5,63.3,56.3,53.1,44.5.HRMS(ESI)m/z calcd forC19H18N4O3(M+Na)+373.1277,found 373.1277.
实施例3：1-苄基-4-对氯苯基-5-(吡唑啉2-酮基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ7.64(d,J＝10.0Hz,2H),7.42-7.37(m,5H),7.31(d,J＝10.0Hz,2H),5.62(s,2H),4.15(t,J＝10.0Hz,2H),2.91(br s,2H).13C NMR(125MHz,CDCl3):δ155.6,141.1,134.9,134.4,129.4,129.4,129.1,128.1,128.0,128.0,127.8,63.3,53.4,44.7.HRMS(ESI)m/z calcd for C18H15ClN4O2(M+Na)+377.0781,found377.0783.
实施例4：1-苄基-4-苯基-5-((S)-4-苯基-吡咯啉2-酮基)-1H-1,2,3-三氮唑
(c＝1.70,CH2Cl2).1H NMR(500MHz,CDCl3,TMS):δ7.50-7.40(m,10H),7.10-7.05(m,1H),6.95-6.85(m,2H),6.42(d,J＝5.0Hz,2H),5.39(m,2H),4.57(s,2H),4.32(t,J＝10.0Hz,1H).13C NMR(125MHz,(CD3)2SO):δ156.3,134.9,134.7,129.3,129.2,128.6,128.6,128.4,128.1,128.0,126.8,99.5,70.0,60.8,50.5.HRMS(ESI)m/zcalcd for C24H20N4O2(M+Na)+419.1484,found 419.1488.
实施例5：1-苄基-4-苯基-5-((S)-4-苄基-吡唑啉2-酮基)-1H-1,2,3-三氮唑
(c＝2.15,CH2Cl2).1H NMR(500MHz,CD3OD,TMS):δ7.65-7.55(m,2H),7.50-7.36(m,10H),7.09-7.03(m,3H),6.51(s,2H),5.55(s,2H),4.33(t,J＝10.0Hz,1H),4.09-4.06(m,2H).13C NMR(125MHz,CDCl3):δ155.3,134.5,134.1,129.6,129.3,129.0,128.8,128.5,128.2,127.5,127.2,127.1,69.1,60.4,53.5,53.1.HRMS(ESI)m/zcalcd for C25H22N4O2(M+Na)+433.1640,found 433.1642.
实施例6：1-苄基-4-正丁基-5-((S)-4-苄基-吡唑啉2-酮基)-1H-1,2,3-三氮唑
(c＝0.44,CH2Cl2).1H NMR(500MHz,CD3OD,TMS):δ7.33-7.27(m,5H),7.20-7.15(m,3H),6.85-6.75(m,2H),5.54(s,2H),4.41-4.14(m,3H),2.65-2.45(m,4H),1.75-1.55(m,2H),1.45-1.30(m,2H),0.93(t,J＝10.0Hz,3H).13C NMR(125MHz,CD3OD):δ157.4,136.1,130.2,129.7,129.2,128.2,69.9,59.7,53.0,39.2,31.7,25.3,23.3,14.2.HRMS(ESI)m/z calcd for C23H26N4O2(M+Na)+413.1953,found 413.1948.
实施例7：1-苄基-4叔丁基-5-(N-苯基-N-叔丁氧羰基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ7.29-7.24(m,7H),7.11-7.09(m,3H),5.34(d,J＝15.0Hz,1H),4.94(d,J＝15.0Hz,1H),1.31(s,9H),1.23(s,9H).13C NMR(125MHz,CDCl3):δ152.0,149.7,140.4,134.3,130.7,129.0,128.9,128.5,128.2,125.0,122.2,83.2,51.3,31.8,29.5,27.9.HRMS(ESI)m/z calcd for C24H30N4O2(M+Na)+429.2267,found 429.2268.
实施例8：1-对氯苄基-4-苯基-5-(吡唑啉2-酮基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ7.68(d,J＝10.0Hz,2H),7.44(t,J＝10.0Hz,2H),7.39-7.36(m,3H),7.27-7.25(m,2H),5.57(s,2H),4.24(t,J＝10.0Hz,2H),3.10(br s,2H).13C NMR(125MHz,CDCl3):δ156.6,141.9,135.0,133.0,129.5,129.3,129.2,129.0,127.9,126.5,63.4,52.2,44.8.HRMS(ESI)m/z calcd for C18H15ClN4O2(M+Na)+377.0781,found 377.0781.
实施例9：1-对甲基苄基-4-苯基-5-(吡唑啉2-酮基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ7.69(d,J＝10.0Hz,2H),7.43(t,J＝10.0Hz,2H),7.36-7.27(m,1H),7.20-7.19(m,4H),5.56(s,2H),4.17(t,J＝10.0Hz,2H),2.98(br s,2H),2.33(s,3H).13C NMR(125MHz,CDCl3):δ156.7,141.9,138.9,131.3,129.9,129.5,129.1,128.8,127.8,126.4,63.3,52.9,44.7,21.2.HRMS(ESI)m/z calcd for C19H18N4O2(M+Na)+357.1328,found 357.1331.
实施例10：1-对苯甲酸甲酯基-4-苯基-5-(吡唑啉2-酮基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ8.26(d,J＝10.0Hz,2H),7.78(d,J＝5.0Hz,2H),7.74(d,J＝10.0Hz,2H),7.52-7.49(m,2H),7.45-7.43(m,1H),4.45(t,J＝10.0Hz,2H),3.98(s,3H),3.60(t,J＝10.0Hz,2H).13C NMR(125MHz,CDCl3):δ166.8,156.5,143.2,138.5,131.9,131.4,129.3,129.3,129.0,128.2,126.9,124.2,63.4,52.7,46.1.HRMS(ESI)m/z calcd for C19H16N4O4(M+Na)+387.1069,found 387.1074.
实施例11：1-苯乙基-4-苯基-5-(吡唑啉2-酮基)-1H-1,2,3-三氮唑
1H NMR(500MHz,CDCl3,TMS):δ7.62(d,J＝10.0Hz,2H),7.42(t,J＝10.0Hz,2H),7.36(t,J＝10.0Hz,1H),7.25(t,J＝10.0Hz,2H),7.18(t,J＝5.0Hz,1H),7.08(d,J＝5.0Hz,2H),4.47(t,J＝10.0Hz,2H),4.30(t,J＝10.0Hz,2H),3.29(t,J＝10.0Hz,2H),2.94(br s,2H).13C NMR(125MHz,CDCl3):δ155.8,140.7,137.9,129.6,129.1,129.0,128.9,128.8,128.4,127.1,126.6,63.5,49.5,44.9,36.4.HRMS(ESI)m/z calcd for C19H18N4O2(M+Na)+357.1328,found 357.1338.

Claims (1)

1.一类新型的5-酰胺基-1,4,5-三取代的1,2,3-三氮唑，其特征在于，5-酰胺基-1,4,5-三取代的1,2,3-三氮唑的化学结构式如下：
其中，R1和R2为氢原子、烷基、烷氧基或芳基，R1和R2相同或不同；
R3为烷基、烷氧基或芳基；
R4为烷基或芳基。
CN201711084614.2A 2017-11-07 2017-11-07 一类新型的5-酰胺基-1,4,5-三取代的1,2,3-三氮唑 Withdrawn CN107987067A (zh)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1745009A1 (de) * 2004-05-10 2007-01-24 Grünenthal GmbH Heteroarylsubstituierte cyclohexyl-1,4-diamin-derivate
CN103275023A (zh) * 2013-06-08 2013-09-04 浙江工业大学 1-芳基-1,2,3-三氮唑类化合物及其制备和应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1745009A1 (de) * 2004-05-10 2007-01-24 Grünenthal GmbH Heteroarylsubstituierte cyclohexyl-1,4-diamin-derivate
CN103275023A (zh) * 2013-06-08 2013-09-04 浙江工业大学 1-芳基-1,2,3-三氮唑类化合物及其制备和应用

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BRANT C. BOREN ET AL.: ""Ruthenium-Catalyzed Azide-Alkyne Cycloaddition:Scope and Mechanism"", 《J. AM. CHEM. SOC.》 *
SERENA FERRINI ET AL.: ""Ruthenium-Catalyzed Synthesis of 5-Amino-1,2,3-triazole-4-carboxylates for Triazole-Based Scaffolds: Beyond the Dimroth Rearrangement"", 《THE JOURNAL OF ORGANIC CHEMISTRY》 *
YUN LIAO ET AL.: ""Rhodium-Catalyzed Azide−Alkyne Cycloaddition of Internal Ynamides: Regioselective Assembly of 5-Amino-Triazoles under Mild Conditions"", 《ACS CATALYSIS》 *
张怀远 等: ""N-(2-氨乙基)-1-对氯苯基-5-甲基-1,2,3-三唑-4-甲酰胺的合成"", 《精细化工中间体》 *

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