CN115124542A - 羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法 - Google Patents

羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法 Download PDF

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CN115124542A
CN115124542A CN202210804999.XA CN202210804999A CN115124542A CN 115124542 A CN115124542 A CN 115124542A CN 202210804999 A CN202210804999 A CN 202210804999A CN 115124542 A CN115124542 A CN 115124542A
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pyrazolone
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范学森
王克林
宋霞
张新迎
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Henan Normal University
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Abstract

本发明公开了羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物合成新方法，属于有机合成技术领域。以N‑苯氧基乙酰胺类化合物1和重氮吡唑酮类化合物2为原料，在铑催化剂和添加剂存在下，有机溶剂中加热反应，得到羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物3；本发明通过易得N‑苯氧基乙酰胺类化合物和重氮吡唑酮之间的一锅串联反应，高效合成羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物。该合成方法具有原料简单易得、操作简便、底物适用范围广等优点。

Description

羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法
技术领域
本发明属于有机合成技术领域，具体涉及羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法。
背景技术
螺环化合物具有较高刚性和独特三维结构，螺环的引入可有效地改善母体化合物的理化性能和生物活性。在众多螺环类化合物中，吲唑[螺]吡唑酮具有丰富且显著的药物活性和发光性能，从而在药物化学、农药化学、精细化学品化学等领域得到了广泛应用。
尽管吲唑[螺]吡唑酮类化合物具有重要的应用价值，但其现有的合成方法却很有限，且存在步骤繁琐、条件苛刻、官能团耐受性差等不足之处。
因此，研究并开发从价廉易得的原料出发，在相对温和的反应条件下通过简单操作合成吲唑[螺]吡唑酮类化合物的新方法，具有重要的研究意义。
发明内容
本发明主要提供了一种合成羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的新方法，通过易得N-苯氧基乙酰胺类化合物和重氮吡唑酮类化合物之间的一锅串联反应，高效合成羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物。合成方法具有原料简单易得、操作简便、底物适用范围广等优点。
本发明所合成的羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物，其结构通式为：
Figure BDA0003736666710000011
其中，R1为氢、C1-6链状烷基、C1-4烷氧基、苯基、取代苯基、C1-4烷氧羰基或卤素，取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、三氟甲基或卤素， R1为一元或二元取代，R2为氢、C1-6链状烷基、C1-4烷氧基、三氟甲基或卤素， R3为C1-4烷基。
本发明还提供了上述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，采用的技术方案为：
羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，包括如下操作：以N-苯氧基乙酰胺类化合物1和重氮吡唑酮类化合物2为原料，在铑催化剂和添加剂存在下，有机溶剂中加热反应，得到羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物3；反应方程式为：
Figure BDA0003736666710000021
其中，R1为氢、C1-6链状烷基、C1-4烷氧基、苯基、取代苯基、C1-4烷氧羰基或卤素，取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、三氟甲基或卤素， R1为一元或二元取代，R2为氢、C1-6链状烷基、C1-4烷氧基、三氟甲基或卤素， R3为C1-4烷基。
进一步地，在上述技术方案中，所述有机溶剂为起到溶解原料的作用，优选 1,2-二氯乙烷、三氯甲烷或二氯甲烷。
进一步地，在上述技术方案中，所述铑催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体([RhCp*Cl2]2)或三(乙腈)(五甲基环戊二烯基)铑(III)二(六氟锑酸盐)([RhCp*(MeCN)3](SbF6)2)。
进一步地，在上述技术方案中，所述添加剂为醋酸铯或氟化铯。
进一步地，在上述技术方案中，所述添加剂还包括磷酸钾、磷酸二氢钾、磷酸氢钾或醋酸钾。
进一步地，在上述技术方案中，所述N-苯氧基乙酰胺类化合物1、重氮吡唑酮类化合物2、铑催化剂与添加剂摩尔比为1-1.2:1-3:0.02-0.07:0.1-3。
进一步地，在上述技术方案中，所述反应在空气氛围下进行；反应温度为 40-70℃。
发明有益效果：
本发明与现有技术相比具有以下优点：(1)通过N-苯氧基乙酰胺类化合物和重氮吡唑酮类化合物的一锅串联反应，即可从简单易得的底物直接构建螺杂环骨架，合成过程简单、高效；(2)原料价廉易得；(3)氧化还原中性条件，无需氧化剂，操作简便，底物的适用范围广。
附图说明
图1为实施例1中化合物3a的X-射线单晶衍射图。
具体实施方式
以下通过实施例对本发明的上述内容做进一步详细说明，但不应该将此理解为本发明上述主题的范围仅限于以下的实施例，凡基于本发明上述内容实现的技术均属于本发明的范围。
实施例1
Figure BDA0003736666710000031
向15mL反应管中依次加入化合物1a、有机溶剂、催化剂、添加剂1和/或添加剂2以及化合物2a，在空气条件下将反应管密封，将其置于加热模块中升温搅拌反应。待反应结束后，冷却至室温，加入水淬灭反应，用二氯甲烷萃取，有机相干燥后，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1)得白色固体产物3a。
通过改变反应的溶剂、催化剂、添加剂1、添加剂2、反应温度以及物料比等反应条件，得到一系列的结果，见表1。
表1不同条件下3a的合成a
Figure 1
Figure BDA0003736666710000041
实施例2
Figure BDA0003736666710000042
向15mL反应管中，依次加入1a(30.2mg,0.2mmol)、二氯乙烷(2mL)、[RhCp*Cl2]2(3.1mg,0.005mmol)、CsOAc(38.4mg,0.2mmol)、K3PO4(42.5 mg,0.2mmol)和2a(88.1mg,0.44mmol)，在空气氛围中将反应管密封，并置于50℃反应模块中搅拌反应24h。反应结束后，将反应体系冷却至室温，加入水淬灭反应，用二氯甲烷萃取，有机相干燥后，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1)得白色固体产物3a(56.7mg,65％)。1H NMR(CDCl3,400 MHz):δ9.55(s,1H),7.96-7.92(m,3H),7.57(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.51 -7.46(m,2H),7.32-7.22(m,3H),7.14(d,J＝7.6Hz,1H),7.12-7.07(m,2H),6.91 (td,J1＝7.6Hz,J2＝1.2Hz,1H),2.22(s,3H),2.11(s,3H).13C{1H}NMR(CDCl3, 150MHz):δ166.4,159.6,156.4,156.0,143.9,137.2,134.7,131.9,129.3,129.2, 129.0,126.3,126.2,125.9,122.2,120.1,119.8,118.7,118.4,113.4,112.9,74.4,13.6, 11.8.HRMS(ESI)m/z:[M+H]+Calcd for C26H21N4O3437.1608；Found 437.1604.
实施例3
依照实施例2的方法和步骤a,b，通过改变反应物1和反应物2，合成得到各种羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物3a-3aa，具体结果如下：
Figure BDA0003736666710000051
Figure BDA0003736666710000061
a反应条件:1a(0.2mmol),2a(0.44mmol),[RhCp*Cl2]2(0.005mmol),K3PO4(0.2mmol),CsOAc(0.2mmol)，二氯乙烷(2mL),50℃,24h,空气氛围；b分离收率。
代表性产物表征数据如下：
2'-(2-Hydroxy-5-methylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3b)
1H NMR(DMSO-d6,400MHz):δ9.36(s,1H),7.85(d,J＝7.6Hz,2H),7.72(d,J＝8.0Hz,1H),7.63(t,J＝8.0Hz,1H),7.52(t,J＝8.0Hz,2H),7.43(d,J＝8.0Hz,1H), 7.35-7.28(m,2H),7.03-6.97(m,2H),6.81(d,J＝8.0Hz,1H),2.22(s,3H),2.13(s, 3H),1.97(s,3H).13C{1H}NMR(DMSO-d6,100MHz):δ167.4,161.0,157.9,153.1, 148.8,137.3,135.5,132.2,132.0,129.9,129.8,127.8,126.7,126.4,126.2,123.7, 119.6,117.2,116.5,112.6,111.7,74.6,20.5,13.8,12.3.HRMS(ESI)m/z:[M+Na]+ Calcd forC27H22N4NaO3473.1584；Found 473.1569.
2'-(2-Hydroxy-5-isopropylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9 '-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3c)
1H NMR(CDCl3,400MHz):δ9.30(s,1H),7.96-7.91(m,3H),7.56(t,J＝7.6Hz,1H),7.48(t,J＝8.4Hz,2H),7.32-7.24(m,2H),7.14(d,J＝7.6Hz,1H),7.10(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.00(d,J＝8.4Hz,1H),6.94(d,J＝2.0Hz,1H), 2.88-2.81(m,1H),2.23(s,3H),2.10(s,3H),1.21(d,J＝7.2Hz,6H).13C{1H} NMR(CDCl3,100MHz):δ166.4,159.6,156.5,153.9,143.8,140.4,137.2,134.7, 131.9,129.3,127.3,126.9,126.3,126.1,125.9,122.2,119.5,118.7,117.9,113.4, 113.2,74.3,33.3,24.3,24.2,13.6,11.9.HRMS(ESI)m/z:[M+Na]+Calcd for C29H26 N4NaO3501.1897；Found 501.1879.
2'-(5-(tert-Butyl)-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3d)
1H NMR(CDCl3,600MHz):δ9.37(s,1H),7.96-7.92(m,3H),7.57(t,J＝7.8Hz, 1H),7.48(t,J＝7.8Hz,2H),7.31-7.27(m,3H),7.14(d,J＝7.8Hz,1H),7.09(d,J＝ 2.4Hz,1H),7.01(d,J＝8.4Hz,1H),2.24(s,3H),2.10(s,3H),1.29(s,9H).13C{1H} NMR(CDCl3,150MHz):δ166.4,159.5,156.5,153.6,143.7,142.6,137.2,134.7, 131.9,129.3,126.3,126.2,126.1,126.0,125.9,122.2,119.1,118.7,117.5,113.40, 113.38,74.3,34.1,31.6,13.6,11.9.HRMS(ESI)m/z:[M+Na]+Calcd for C30H28N4 NaO3515.2054；Found515.2041.
2'-(4-Hydroxy-[1,1'-biphenyl]-3-yl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3e)
1H NMR(CDCl3,600MHz):δ9.69(s,1H),7.95-7.92(m,3H),7.57(t,J＝7.8Hz, 1H),7.51(d,J＝7.2Hz,2H),7.48-7.46(m,3H),7.39(t,J＝7.8Hz,2H),7.31-7.25 (m,4H),7.15-7.13(m,2H),2.27(s,3H),2.11(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ166.4,159.5,156.4,155.7,143.9,140.9,137.2,134.6,133.3,131.9,129.3, 128.8,128.0,127.7,126.8,126.7,126.4,126.2,125.9,122.3,120.1,118.7,118.6, 113.4,112.7,74.4,13.6,12.0.HRMS(ESI)m/z:[M+Na]+Calcd for C32H24N4NaO3 535.1741；Found 535.1716.
2'-(5-Fluoro-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3f)
1H NMR(CDCl3,400MHz):δ9.40(s,1H),7.96-7.91(m,3H),7.58(td,J1＝8.0Hz, J2＝1.2Hz,1H),7.50-7.46(m,2H),7.32-7.28(m,2H),7.15(d,J＝7.6Hz,1H), 7.03-6.99(m,1H),6.93(td,J1＝8.8Hz,J2＝2.8Hz,1H),6.80(dd,J1＝9.6Hz,J2＝ 3.2Hz,1H),2.23(s,3H),2.11(s,3H).13C{1H}NMR(CDCl3,150MHz):δ166.2, 159.1,156.5(d,1JC-F＝236.3Hz),156.2,152.1(d,4JC-F＝2.3Hz),143.8,137.1,134.5, 131.9,129.3,126.4,126.3,125.8,122.2,120.7(d,3JC-F＝8.9Hz),119.3(d,3JC-F＝8.7 Hz),118.7,115.6(d,2JC-F＝23.0Hz),114.7(d,2JC-F＝23.1Hz),113.4,111.9,74.4, 13.6,11.7.19F NMR(376MHz,CDCl3)δ:-124.59--124.65.HRMS(ESI)m/z: [M+Na]+Calcd for C26H19FN4NaO3477.1333；Found477.1313.
2'-(5-Chloro-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3g)
1H NMR(CDCl3,400MHz):δ9.69(s,1H),7.95-7.91(m,3H),7.58(td,J1＝8.0Hz, J2＝1.2Hz,1H),7.50-7.46(m,2H),7.33-7.26(m,2H),7.19-7.14(m,2H),7.06(d,J ＝2.4Hz,1H),7.00(d,J＝8.8Hz,1H),2.24(s,3H),2.12(s,3H).13C{1H}NMR (CDCl3,100MHz):δ166.2,159.1,156.2,154.8,143.8,137.1,134.5,131.9,129.3, 128.9,128.2,126.4,126.3,125.8,124.7,122.2,121.1,119.9,118.7,113.4,111.6,74.4, 13.6,11.8.HRMS(ESI)m/z:[M+Na]+Calcd for C26H19ClN4NaO3493.1038；Found 493.1019.
2'-(5-Bromo-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3h)
1H NMR(CDCl3,400MHz):δ9.72(s,1H),7.95-7.91(m,3H),7.60-7.56(m,1H),7.50-7.46(m,2H),7.32-7.26(m,3H),7.20(d,J＝2.4Hz,1H),7.15(d,J＝7.6Hz, 1H),6.94(d,J＝8.8Hz,1H),2.24(s,3H),2.12(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ166.2,159.1,156.2,155.3,143.8,137.1,134.5,131.9,131.8,131.1,129.3, 126.4,126.3,125.8,122.3,121.6,120.5,118.7,113.4,111.9,111.5,74.4,13.6,11.7. HRMS(ESI)m/z:[M+Na]+Calcd for C26H19BrN4NaO3537.0533；Found 537.0522.
2'-(2-Hydroxy-5-iodophenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-pyr azolo[1,2-a]indazole]-3',5(1H)-dione(3i)
1H NMR(CDCl3,400MHz):δ9.76(s,1H),7.95-7.91(m,3H),7.60-7.56(m,1H),7.51-7.47(m,3H),7.38(d,J＝2.0Hz,1H),7.33-7.29(m,2H),7.15(d,J＝8.0Hz, 1H),6.83(d,J＝8.8Hz,1H),2.23(s,3H),2.12(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ166.2,159.1,156.2,156.1,143.7,137.7,137.1,134.5,131.9,129.3,126.4, 126.3,125.8,122.2,122.1,121.2,118.7,113.4,111.3,81.6,74.4,13.6,11.7.HRMS (ESI)m/z:[M+Na]+Calcdfor C26H19IN4NaO3585.0394；Found 585.0378.
Ethyl 3-(1',3-dimethyl-3',5-dioxo-1-phenyl-1,5-dihydro-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazol]-2'-yl)-4-hydroxybenzoate(3j)
1H NMR(CDCl3,400MHz):δ10.5(s,1H),7.96-7.90(m,4H),7.86(d,J＝2.0Hz, 1H),7.59(td,J1＝8.0Hz,J2＝0.8Hz,1H),7.50-7.46(m,2H),7.32-7.27(m,2H), 7.16(d,J＝8.0Hz,1H),7.06(d,J＝8.4Hz,1H),4.33(q,J＝7.2Hz,2H),2.27(s, 3H),2.13(s,3H),1.36(t,J＝7.2Hz,3H).13C{1H}NMR(CDCl3,100MHz):δ166.4, 166.2,160.6,159.3,156.2,143.9,137.1,134.4,131.9,130.9,130.7,129.3,126.44, 126.37,125.8,122.3,122.2,119.5,118.7,118.2,113.4,111.8,74.4,60.7,14.4,13.6, 11.8.HRMS(ESI)m/z:[M+Na]+Calcd for C29H24N4NaO5531.1639；Found 531.1626.
2'-(2-Hydroxy-4-methylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3k)
1H NMR(CDCl3,400MHz):δ9.48(s,1H),7.95-7.91(m,3H),7.56(t,J＝7.6Hz, 1H),7.47(t,J＝8.4Hz,2H),7.31-7.25(m,2H),7.13(d,J＝7.6Hz,1H),6.98(d,J＝ 7.6Hz,1H),6.90(s,1H),6.73(d,J＝8.0Hz,1H),2.32(s,3H),2.20(s,3H),2.09(s, 3H).13C{1H}NMR(CDCl3,150MHz):δ166.5,159.7,156.5,155.9,143.7,139.5, 137.2,134.7,131.8,129.3,128.8,126.3,126.1,125.9,122.2,121.0,120.3,118.7, 115.3,113.4,113.0,74.4,21.2,13.6,11.8.HRMS(ESI)m/z:[M+Na]+Calcd for C27H22N4NaO3473.1584；Found 473.1567.
2'-(2-Hydroxy-4-isopropylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9 '-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3l)
1H NMR(CDCl3,400MHz):δ9.50(s,1H),7.95-7.91(m,3H),7.56(t,J＝8.0Hz, 1H),7.47(t,J＝8.0Hz,2H),7.31-7.23(m,2H),7.12(d,J＝7.6Hz,1H),7.02(d,J＝ 7.6Hz,1H),6.96(d,J＝1.6Hz,1H),6.78(dd,J1＝8.0Hz,J2＝1.2Hz,1H), 2.90-2.84(m,1H),2.21(s,3H),2.09(s,3H),1.25(d,J＝6.8Hz,6H).13C{1H}NMR (CDCl3,150MHz):δ166.5,159.8,156.5,155.9,150.5,143.8,137.2,134.7,131.8, 129.3,128.8,126.3,126.1,125.9,122.2,118.7,118.5,117.6,115.6,113.4,113.0,74.4, 33.8,23.84,23.82,13.6,11.9.HRMS(ESI)m/z:[M+Na]+Calcd for C29H26N4NaO3 501.1897；Found 501.1881.
2'-(3-Hydroxy-[1,1'-biphenyl]-4-yl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3m)
1H NMR(CDCl3,400MHz):δ9.77(s,1H),7.96-7.92(m,3H),7.63-7.61(m,2H),7.59-7.55(m,1H),7.48(t,J＝8.4Hz,2H),7.42(t,J＝7.6Hz,2H),7.34-7.25(m, 4H),7.17-7.13(m,3H),2.25(s,3H),2.10(s,3H).13C{1H}NMR(CDCl3,100MHz): δ166.4,159.6,156.4,156.3,143.8,142.1,140.4,137.2,134.6,131.9,129.3,129.27, 128.8,127.4,127.0,126.4,126.2,125.9,122.2,118.8,118.7,118.2,117.4,113.4, 112.6,74.4,13.6,11.9.HRMS(ESI)m/z:[M+Na]+Calcd for C32H24N4NaO3535.1741； Found 535.1720.
2'-(4-Bromo-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3n)
1H NMR(CDCl3,400MHz):δ9.97(s,1H),7.95-7.90(m,3H),7.58(t,J＝7.6Hz, 1H),7.48(t,J＝8.4Hz,2H),7.32-7.23(m,3H),7.15(d,J＝8.0Hz,1H),7.03(dd,J1＝8.4Hz,J2＝2.0Hz,1H),6.95(d,J＝8.0Hz,1H),2.20(s,3H),2.11(s,3H).13C{1H} NMR(CDCl3,100MHz):δ166.2,159.2,157.1,156.2,143.6,137.1,134.5,131.9, 129.7,129.3,126.4,126.3,125.8,123.1,123.0,122.3,122.2,118.7,117.5,113.4, 112.0,74.4,13.6,11.8.HRMS(ESI)m/z:[M+Na]+Calcd for C26H19BrN4NaO3 537.0533；Found 537.0526.
2'-(2-Hydroxy-4,5-dimethylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3o)
1H NMR(CDCl3,600MHz):δ9.23(s,1H),7.95(d,J＝8.4Hz,2H),7.91(d,J＝8.4 Hz,1H),7.55(t,J＝7.8Hz,1H),7.48(t,J＝7.8Hz,2H),7.31-7.24(m,2H),7.13(d, J＝7.8Hz,1H),6.87(s,1H),6.85(s,1H),2.23(s,3H),2.21(s,3H),2.18(s,3H), 2.10(s,3H).13C{1H}NMR(CDCl3,150MHz):δ166.5,159.8,156.6,153.8,143.7, 137.8,137.2,134.8,131.8,129.8,129.3,127.9,126.3,126.0,125.9,122.2,120.8, 118.7,115.4,113.4,113.0,74.4,19.6,18.9,13.6,11.9.HRMS(ESI)m/z:[M+Na]+ Calcd for C28H24N4NaO3487.1741；Found 487.1721.
2'-(2-Hydroxy-3-methylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3p)
1H NMR(CDCl3,600MHz):δ9.40(s,1H),7.95-7.92(m,3H),7.57(t,J＝7.8Hz, 1H),7.48(t,J＝8.4Hz,2H),7.30(t,J＝7.8Hz,1H),7.27-7.25(m,1H),7.14-7.11 (m,2H),6.94(d,J＝7.2Hz,1H),6.82(t,J＝7.8Hz,1H),2.33(s,3H),2.20(s,3H), 2.09(s,3H).13C{1H}NMR(CDCl3,100MHz):δ166.4,159.6,156.5,154.2,144.0, 137.2,134.7,131.8,130.4,129.3,128.6,126.8,126.3,126.1,125.9,122.2,119.7, 118.7,117.8,113.4,113.2,74.4,16.7,13.6,11.8.HRMS(ESI)m/z:[M+Na]+Calcd for C27H22N4NaO3473.1584；Found473.1564.
2'-(2-Hydroxyphenyl)-1',3,7'-trimethyl-1-(p-tolyl)-3'H-spiro[pyrazole-4,9'-pyrazo lo[1,2-a]indazole]-3',5(1H)-dione(3q)
1H NMR(CDCl3,400MHz):δ9.67(s,1H),7.84-7.78(m,3H),7.35(dd,J1＝8.0Hz, J2＝0.4Hz,1H),7.28(d,J＝8.4Hz,2H),7.25-7.21(m,1H),7.11-7.06(m,2H), 6.92-6.88(m,2H),2.39(s,3H),2.37(s,3H),2.20(s,3H),2.08(s,3H).13C{1H} NMR(CDCl3,100MHz):δ166.3,159.3,156.4,156.1,143.4,136.6,136.2,134.8, 132.5,132.4,129.8,129.1,129.0,126.1,122.5,120.0,119.8,118.7,118.5,113.1, 112.8,74.3,21.2,21.0,13.6,11.7.HRMS(ESI)m/z:[M+Na]+Calcd for C28H24N4Na O3487.1741；Found 487.1721.
7'-Ethyl-1-(4-ethylphenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyrazol e-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3r)
1H NMR(CDCl3,600MHz):δ9.69(s,1H),7.87(d,J＝8.4Hz,2H),7.81(d,J＝8.4 Hz,1H),7.38(d,J＝7.8Hz,1H),7.31(d,J＝8.4Hz,2H),7.23-7.20(m,1H), 7.11-7.05(m,2H),6.91-6.88(m,2H),2.71-2.63(m,4H),2.20(s,3H),2.08(s,3H), 1.26(t,J＝7.8Hz,3H),1.21(t,J＝7.8Hz,3H).13C{1H}NMR(CDCl3,150MHz):δ 166.4,159.3,156.4,156.1,143.5,143.0,142.6,135.0,132.6,131.3,129.1,129.0, 128.6,126.1,121.3,120.0,119.7,118.8,118.5,113.2,112.7,74.4,28.6,28.5,15.7, 15.5,13.6,11.7.HRMS(ESI)m/z:[M+H]+Calcd for C30H29N4O3493.2234；Found 493.2214.
7'-(tert-Butyl)-1-(4-(tert-butyl)phenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-sp iro[pyrazole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3s)
1H NMR(CDCl3,400MHz):δ9.68(s,1H),7.90(d,J＝8.8Hz,2H),7.82(d,J＝8.4 Hz,1H),7.59(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.51(d,J＝8.8Hz,2H),7.24-7.20 (m,1H),7.11-7.04(m,3H),6.92-6.88(m,1H),2.20(s,3H),2.08(s,3H),1.36(s,9H), 1.29(s,9H).13C{1H}NMR(CDCl3,150MHz):δ166.4,159.3,156.5,156.1,150.3, 149.5,143.6,134.8,132.4,129.1,129.06,129.02,126.2,125.9,120.2,119.8,118.61, 118.55,118.51,112.9,112.8,74.5,35.1,34.7,31.4,31.3,13.6,11.7.HRMS(ESI)m/z: [M+Na]+Calcd forC34H36N4NaO3571.2680；Found 571.2661.
2'-(2-Hydroxyphenyl)-7'-methoxy-1-(4-methoxyphenyl)-1',3-dimethyl-3'H-spiro[ pyrazole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3t)
1H NMR(CDCl3,400MHz):δ9.71(s,1H),7.84-7.82(m,3H),7.25-7.21(m,1H),7.11-7.06(m,3H),7.01-6.98(m,2H),6.92-6.88(m,1H),6.64(d,J＝2.4Hz,1H), 3.85(s,3H),3.81(s,3H),2.20(s,3H),2.09(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ166.0,159.2,158.3,157.9,156.3,156.1,143.2,130.4,129.1,129.0,128.4, 127.2,120.5,120.0,119.8,118.5,116.5,114.4,114.2,112.9,108.4,74.3,56.1,55.6, 13.6,11.7.HRMS(ESI)m/z:[M+Na]+Calcd for C28H24N4NaO5519.1639；Found 519.1619.
7'-Fluoro-1-(4-fluorophenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyra zole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3u)
1H NMR(CDCl3,400MHz):δ9.39(s,1H),7.94-7.88(m,3H),7.32-7.22(m,2H),7.19-7.15(m,2H),7.11-7.06(m,2H),6.94-6.87(m,2H),2.20(s,3H),2.14(s,3H). 13C{1H}NMR(CDCl3,100MHz):δ165.8,160.6(d,1JC-F＝245.5Hz),160.5(d,1JC-F＝247.0Hz),159.8,156.2,156.0,144.5,133.1(d,4JC-F＝2.9Hz),131.2(d,4JC-F＝2.2 Hz),129.4,129.0,127.1(d,3JC-F＝8.6Hz),120.5(d,3JC-F＝8.7Hz),120.2,119.8, 119.0(d,2JC-F＝23.8Hz),118.1,116.2(d,2JC-F＝23.1Hz),114.6(d,3JC-F＝8.0Hz), 113.3,110.2(d,2JC-F＝26.7Hz),74.2(d,4JC-F＝2.9Hz),13.7,11.8.19F NMR(376 MHz,CDCl3)δ:-113.51--113.56(m),-114.63--114.70(m).HRMS(ESI)m/z: [M+Na]+Calcd for C26H18F2N4NaO3495.1239；Found 495.1223.
7'-Chloro-1-(4-chlorophenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyra zole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3v)
1H NMR(CDCl3,400MHz):δ9.28(s,1H),7.93-7.90(m,2H),7.86(d,J＝8.4Hz, 1H),7.55(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.46-7.43(m,2H),7.27-7.23(m,1H), 7.11-7.06(m,3H),6.92(td,J1＝7.6Hz,J2＝1.2Hz,1H),2.19(s,3H),2.15(s,3H). 13C{1H}NMR(CDCl3,100MHz):δ165.8,159.9,156.3,155.9,144.7,135.5,133.3, 132.2,131.8,131.7,129.5,129.4,129.1,127.1,122.6,120.2,119.9,119.8,118.0, 114.3,113.4,74.1,13.7,11.9.HRMS(ESI)m/z:[M+Na]+Calcd for C26H18Cl2N4Na O3527.0648；Found 527.0633.
7'-Bromo-1-(4-bromophenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyra zole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3w)
1H NMR(CDCl3,400MHz):δ9.26(s,1H),7.86(d,J＝8.8Hz,2H),7.80(d,J＝8.8 Hz,1H),7.70(dd,J1＝8.8Hz,J2＝2.0Hz,1H),7.60(d,J＝8.8Hz,2H),7.27-7.24 (m,2H),7.10-7.06(m,2H),6.94-6.90(m,1H),2.19(s,3H),2.14(s,3H).13C{1H} NMR(CDCl3,100MHz):δ165.8,159.9,156.4,155.9,144.7,136.0,135.1,133.7, 132.4,129.5,129.1,127.4,125.4,120.2,120.1,119.9,119.5,118.8,118.0,114.7, 113.4,74.0,13.7,11.9.HRMS(ESI)m/z:[M+Na]+Calcd for C26H18Br2N4NaO3 614.9638；Found 614.9632.
2'-(2-Hydroxyphenyl)-1',3-dimethyl-7'-(trifluoromethyl)-1-(4-(trifluoromethyl)p henyl)-3'H-spiro[pyrazole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3x)
1H NMR(CDCl3,400MHz):δ9.03(s,1H),8.13(d,J＝8.8Hz,2H),8.04(d,J＝8.4 Hz,1H),7.88(d,J＝8.4Hz,1H),7.75(d,J＝8.4Hz,2H),7.35(s,1H),7.29-7.24(m, 1H),7.12-7.07(m,2H),6.94(td,J1＝7.6Hz,J2＝1.2Hz,1H),2.22(s,3H),2.19(s, 3H).13C{1H}NMR(CDCl3,150MHz):δ166.1,160.2,156.6,155.9,145.8,139.6, 137.1,129.9(q,3JC-F＝4.4Hz),129.7,129.1,128.6(q,2JC-F＝32.9Hz),128.3(q, 2JC-F＝32.9Hz),126.6(q,3JC-F＝4.4Hz),126.2,123.8(q,1JC-F＝270.1Hz),123.2(q, 1JC-F＝270.1Hz),120.4,119.9,119.6(q,3JC-F＝4.4Hz),118.4,117.7,113.63,113.61, 74.2,13.8,12.0.19F NMR(376MHz,CDCl3)δ:-61.82(s),-62.39(s).HRMS(ESI) m/z:[M+Na]+Calcd forC28H18F6N4NaO3595.1175；Found 595.1166.
2'-(2-Hydroxyphenyl)-1',3,6'-trimethyl-1-(m-tolyl)-3'H-spiro[pyrazole-4,9'-pyraz olo[1,2-a]indazole]-3',5(1H)-dione(3y)
1H NMR(DMSO-d6,400MHz):δ9.63(s,1H),7.67-7.63(m,2H),7.56(s,1H),7.39 (t,J＝8.0Hz,1H),7.27(d,J＝8.0Hz,1H),7.23-7.10(m,4H),6.91(d,J＝8.0Hz, 1H),6.86(t,J＝7.6Hz,1H),2.43(s,3H),2.37(s,3H),2.11(s,3H),1.96(s,3H). 13C{1H}NMR(CDCl3,100MHz):δ166.4,159.4,156.4,156.1,143.6,142.9,139.4, 137.2,134.7,129.2,129.1,129.0,127.1,126.9,123.1,121.8,120.0,119.8,119.3, 118.4,115.9,113.9,112.7,74.2,21.7,21.6,13.5,11.7.HRMS(ESI)m/z:[M+Na]+ Calcd for C28H24N4NaO3487.1741；Found 487.1725.
2-(2-Hydroxyphenyl)-1,3'-dimethyl-1'-(naphthalen-2-yl)-3H-spiro[benzo[f]pyraz olo[1,2-a]indazole-11,4'-pyrazole]-3,5'(1'H)-dione(3z)
1H NMR(CDCl3,400MHz):δ8.46(d,J＝2.0Hz,1H),8.31(s,1H),8.18-8.15(m, 1H),7.98-7.95(m,2H),7.89(t,J＝7.6Hz,2H),7.79(d,J＝8.0Hz,1H),7.66(s,1H), 7.63-7.59(m,1H),7.56-7.49(m,3H),7.27-7.23(m,1H),7.15-7.09(m,2H),6.93(td, J1＝7.6Hz,J2＝1.2Hz,1H),2.28(s,3H),2.18(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ166.7,159.3,156.9,156.1,143.4,134.75,134.71,133.4,131.5,131.0,130.9, 129.4,129.3,129.0,128.6,128.51,128.47,128.1,127.8,127.1,126.7,126.2,126.1, 122.6,120.1,119.9,118.4,117.7,116.3,113.1,110.3,73.9,13.7,11.8.HRMS(ESI) m/z:[M+Na]+Calcd forC34H24N4NaO3559.1741；Found 559.1736.
1',3-Diethyl-2'-(2-hydroxyphenyl)-1-phenyl-3'H-spiro[pyrazole-4,9'-pyrazolo[1,2- a]indazole]-3',5(1H)-dione(3aa)
1H NMR(CDCl3,400MHz):δ9.50(s,1H),7.98-7.92(m,3H),7.55(td,J1＝8.0Hz, J2＝1.2Hz,1H),7.48(t,J＝8.4Hz,2H),7.32-7.22(m,3H),7.16-7.11(m,2H),7.07 (dd,J1＝8.4Hz,J2＝1.2Hz,1H),6.91(td,J1＝7.6Hz,J2＝1.2Hz,1H),2.60-2.48 (m,2H),2.44-2.36(m,1H),2.33-2.23(m,1H),1.24-1.16(m,6H).13C{1H}NMR (CDCl3,100MHz):δ166.8,160.9,159.9,155.9,150.0,137.3,134.4,131.7,129.30, 129.27,128.6,126.5,126.3,126.1,122.1,120.2,119.8,118.8,118.6,113.4,112.2, 74.4,21.6,19.5,12.6,9.3.HRMS(ESI)m/z:[M+Na]+Calcd for C28H24N4NaO3 487.1741；Found487.1727.
实施例4
本发明所合成的产物羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物3进行系列反应，从而合成进一步的衍生物。例如：
向15mL反应管中，依次加入3a(43.6mg,0.1mmol)、DMF(1mL)、MeI(29.8 mg,0.21mmol)和K2CO3(27.6mg,0.2mmol)，将管密封，并在室温下搅拌反应12 h。加水淬灭反应，并用乙酸乙酯(10mL×3)萃取。合并有机相，用无水硫酸钠干燥，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝1/1)得无色液体产物4 (42.2mg,94％)。
Figure BDA0003736666710000151
1H NMR(CDCl3,400MHz):δ7.95(d,J＝7.6Hz,2H),7.87(d,J＝8.0Hz,1H), 7.51-7.41(m,4H),7.33-7.26(m,2H),7.18-7.15(m,1H),7.07-7.00(m,2H),6.94(d,J ＝8.4Hz,1H),3.80(s,3H),2.08(s,3H),1.94(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ167.4,161.3,157.4,157.1,148.2,137.5,136.0,132.1,131.5,129.3,129.2, 126.3,126.0,125.1,122.1,120.8,118.9,118.7,113.3,111.8,111.2,74.6,55.6,13.6, 12.1.HRMS(ESI)m/z:[M+H]+Calcd for C27H23N4O3Exact Mass:451.1765；Found 451.1748.
向15mL反应管中，依次加入4(42.2mg,0.09mmol)、DME(1mL)、丙烯酸乙酯(19.6μL,0.18mmol)、[RhCp*Cl2]2(2.8mg,0.0045mmol)、AgSbF6(6.2mg, 0.018mmol)和Cu(OAc)2(32.7mg,0.18mmol)，在氩气气氛下将反应管密封，放置在110℃的模块中反应14h。反应结束后，将其冷却至室温，用水淬灭并用乙酸乙酯(10mL×3)萃取。合并有机相，用无水硫酸钠干燥，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得无色液体产物5(23.2mg,47％)。
Figure BDA0003736666710000152
1H NMR(CDCl3,400MHz):δ8.95(d,J＝16.0Hz,1H),7.94(d,J＝8.4Hz, 2H),7.73(d,J＝8.0Hz,1H),7.47-7.44(m,3H),7.34-7.29(m,2H),7.21(t,J＝8.0 Hz,1H),7.04-7.00(m,2H),6.93(d,J＝8.4Hz,1H),6.43(d,J＝16.0Hz,1H),4.26 (q,J＝7.2Hz,2H),3.80(s,3H),2.09(s,3H),1.93(s,3H),1.31(t,J＝7.2Hz,3H). 13C{1H}NMR(CDCl3,150MHz):δ167.4,166.5,161.8,157.5,156.9,150.1,141.4, 137.4,135.9,132.2,129.5,129.2,128.9,128.5,126.1,125.9,123.0,122.6,120.8, 120.1,118.69,118.67,112.8,111.1,74.4,60.6,55.6,14.3,13.7,12.2.HRMS(ESI) m/z:[M+Na]+Calcd forC32H28N4NaO5571.1952；Found 571.1957.
向15mL反应管中，依次加入3a(43.6mg,0.1mmol)、丙酮(1mL)、DMCC (32.3mg,0.3mmol)、Cs2CO3(81.5mg,0.25mmol)和DMAP(2.4mg,0.02mmol)，在氩气气氛下将反应管密封，室温条件下反应10h。反应结束后，加入饱和盐水淬灭，然后将反应混合物转移至分液漏斗中，乙酸乙酯(10mL×3)萃取。合并有机相，用无水硫酸钠干燥，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝1/1)得白色固体产物6(42.1mg,83％)。
Figure BDA0003736666710000161
1H NMR(CDCl3,600MHz):δ7.92(d,J＝7.8Hz,2H),7.87(d,J＝7.8Hz,1H), 7.52-7.50(m,1H),7.46(t,J＝8.4Hz,2H),7.37-7.32(m,2H),7.28-7.22(m,3H), 7.19(t,J＝7.2Hz,1H),7.07(d,J＝7.2Hz,1H),3.00(s,3H),2.91(s,3H),2.11(s, 3H),1.94(s,3H).13C{1H}NMR(CDCl3,100MHz):δ167.0,160.4,157.1,154.5, 150.2,148.0,137.3,135.8,131.8,131.5,129.3,129.2,126.1,126.0,125.3,125.2, 123.2,123.1,122.1,118.7,113.2,111.7,74.5,36.7,36.5,13.6,11.2.HRMS(ESI)m/z: [M+Na]+Calcd forC29H25N5NaO4530.1799；Found 530.1789.
向15mL反应管中，依次加入6(50.8mg,0.1mmol)、DME(1mL)、丙烯酸乙酯(21.7μL,0.2mmol)、[RhCp*Cl2]2(3.1mg,0.005mmol)、AgSbF6(6.9mg,0.02 mmol)和Cu(OAc)2(36.3mg,0.2mmol)，在氩气氛围下将反应管密封，放置于 110℃的模块中反应14h。反应结束后，加入水淬灭，然后将反应混合物转移至分液漏斗中，乙酸乙酯(10mL×3)萃取。合并有机相，无水硫酸钠干燥，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得无色液体产物7(42.9mg, 61％)。
Figure BDA0003736666710000171
1H NMR(DMSO-d6,600MHz):δ8.88(d,J＝16.2Hz,1H),8.13(d,J＝7.8Hz, 1H),8.04(d,J＝7.8Hz,1H),7.65-7.54(m,5H),7.44-7.39(m,3H),7.30(t,J＝7.8 Hz,1H),7.24(d,J＝8.4Hz,1H),6.73-6.69(m,2H),4.21-4.14(m,4H),2.84(s,3H), 2.73(s,3H),2.14(s,3H),2.07(s,3H),1.25(t,J＝7.2Hz,3H),1.20(t,J＝7.2Hz, 3H).13C{1H}NMR(DMSO-d6,100MHz):δ168.6,166.34,166.26,160.6,158.3, 153.9,150.4,150.1,141.6,139.0,135.4,135.2,132.1,131.8,131.0,130.2,129.69, 129.66,128.4,128.1,127.30,127.28,125.7,124.6,123.7,123.5,121.6,121.3,120.3, 112.1,73.3,60.8,60.5,36.6,36.3,14.7,14.6,13.7,11.9.HRMS(ESI)m/z:[M+Na]+ Calcd for C39H37N5NaO8726.2534；Found726.2514.
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。

Claims (8)

1.羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物，其特征在于，结构通式为：
Figure FDA0003736666700000011
其中，R1为氢、C1-6链状烷基、C1-4烷氧基、苯基、取代苯基、C1-4烷氧羰基或卤素，取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、三氟甲基或卤素，R2为氢、C1-6链状烷基、C1-4烷氧基、三氟甲基或卤素，R3为C1-4烷基。
2.如权利要求1所述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，其特征在于，包括如下操作：以N-苯氧基乙酰胺类化合物1和重氮吡唑酮类化合物2为原料，在铑催化剂和添加剂存在下，有机溶剂中加热反应，得到羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物3；反应方程式为：
Figure FDA0003736666700000012
其中，R1为氢、C1-6链状烷基、C1-4烷氧基、苯基、取代苯基、C1-4烷氧羰基或卤素，取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基、三氟甲基或卤素，R1为一元或二元取代，R2为氢、C1-6链状烷基、C1-4烷氧基、三氟甲基或卤素，R3为C1-4烷基。
3.根据权利要求2所述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，其特征在于：反应溶剂选自1,2-二氯乙烷、三氯甲烷或二氯甲烷。
4.根据权利要求2所述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，其特征在于：所述铑催化剂选自[RhCp*Cl2]2或[RhCp*(MeCN)3](SbF6)2。
5.根据权利要求2所述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，其特征在于：所述添加剂选自醋酸铯或氟化铯。
6.根据权利要求5所述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，其特征在于：所述添加剂还包括磷酸钾、磷酸二氢钾、磷酸氢钾或醋酸钾。
7.根据权利要求2所述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，其特征在于：所述N-苯氧基乙酰胺类化合物1、重氮吡唑酮类化合物2、铑催化剂与添加剂摩尔比为1-1.2:1-3:0.02-0.07:0.1-3。
8.根据权利要求2所述羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法，其特征在于：反应在空气氛围下进行；反应温度为40-70℃。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115785096A (zh) * 2022-11-22 2023-03-14 河南师范大学 高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110111046A1 (en) * 2009-11-10 2011-05-12 Pfizer Inc N1-Pyrazolospiroketone Acetyl-CoA Carboxylase Inhibitors
CN107849053A (zh) * 2015-04-03 2018-03-27 卡利拉制药公司 螺环化合物
CN110759920A (zh) * 2019-11-05 2020-02-07 绍兴文理学院 对甲氧基苯基取代含吡唑结构的螺[吲唑-吡唑啉]衍生物及其制备方法与应用
CN111675712A (zh) * 2020-06-23 2020-09-18 河南师范大学 一种吡唑啉酮并苯二氮杂卓类化合物的合成方法
CN113185536A (zh) * 2021-04-29 2021-07-30 河南师范大学 一种吡唑烷酮并苯并1,3-氧氮杂卓类化合物的合成方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110111046A1 (en) * 2009-11-10 2011-05-12 Pfizer Inc N1-Pyrazolospiroketone Acetyl-CoA Carboxylase Inhibitors
CN107849053A (zh) * 2015-04-03 2018-03-27 卡利拉制药公司 螺环化合物
CN110759920A (zh) * 2019-11-05 2020-02-07 绍兴文理学院 对甲氧基苯基取代含吡唑结构的螺[吲唑-吡唑啉]衍生物及其制备方法与应用
CN111675712A (zh) * 2020-06-23 2020-09-18 河南师范大学 一种吡唑啉酮并苯二氮杂卓类化合物的合成方法
CN113185536A (zh) * 2021-04-29 2021-07-30 河南师范大学 一种吡唑烷酮并苯并1,3-氧氮杂卓类化合物的合成方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
XIA SONG ET AL.: ""Coupling partner-dependent unsymmetrical C–H functionalization of N-phenoxyacetamides leading to sophisticated spirocyclic scaffolds"", 《ORGANIC CHEMISTRY FRONTIERS》, vol. 9, pages 4583 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115785096A (zh) * 2022-11-22 2023-03-14 河南师范大学 高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法
CN115785096B (zh) * 2022-11-22 2023-11-28 河南师范大学 高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法

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