CN115838371A - 一种茚并吡唑类化合物的合成方法 - Google Patents
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- 238000000034 method Methods 0.000 claims abstract description 15
- XSTBCICLDQSQIQ-UHFFFAOYSA-N indeno[2,1-c]pyrazole Chemical class C1=CC=C2C3=CN=NC3=CC2=C1 XSTBCICLDQSQIQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 11
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- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 7
- 239000010948 rhodium Substances 0.000 claims abstract description 7
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
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- Y02P20/584—Recycling of catalysts
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Abstract
本发明公开了一种茚并吡唑类化合物的合成方法,属于有机合成技术领域。以芳基偶氮甲碱亚胺类化合物1和4‑乙烯基‑1,3‑二氧环戊‑2‑酮2为原料,在钌或铑催化剂和添加剂存在下,空气氛围下,有机溶剂中升温反应,得到茚并吡唑类化合物3。本发明通过芳基偶氮甲碱亚胺与乙烯基环状碳酸酯的串联反应,高效合成了茚并吡唑类化合物。该方法具有原料简单易得、反应条件温和、官能团相容性好、产物收率高、选择性好、原子经济性高等优点。
Description
技术领域
本发明具体涉及一种茚并吡唑类化合物的合成方法,属于有机合成技术领域。
背景技术
茚并吡唑类化合物具有多种重要的药物活性,如抑制微管蛋白聚合、抗分枝杆菌、抗精神抑郁和消炎等,在新药开发中有着十分广泛的应用。另外,该类化合物还具有独特的分子结构和丰富的反应性能,常用于制备香料、染料和植物生长调节剂等精细化学品。
茚并吡唑类化合物具有重要的研究和应用价值,然而该类化合物的合成方法仍很有限,而且这些文献方法尚存在原料昂贵、条件苛刻、官能团耐受性差等问题。
因此,研究开发从价廉易得原料出发,在温和条件下,高效构建茚并吡唑类分子骨架的新方法仍显得非常必要。
发明内容
为了克服上述存在的技术问题,本发明提供了一种茚并吡唑类化合物的合成方法。该合成方法通过芳基偶氮甲碱亚胺与乙烯基环状碳酸酯的串联反应,高效合成了茚并吡唑类化合物。该方法具有原料简单易得、反应条件温和、官能团相容性好、产物收率高、选择性好、原子经济性高等优点。
本发明所述茚并吡唑类化合物的合成方法,包括如下操作:以芳基偶氮甲碱亚胺类化合物1和4-乙烯基-1,3-二氧环戊-2-酮2为原料,在钌或铑催化剂和添加剂存在下,有机溶剂中升温反应,得到茚并吡唑类化合物3;反应方程式表示为:
其中R1为氢、C1-4烷基、C1-4烷氧基、卤素或三氟甲基,R1为一元或二元取代,R2为氢或C1-4烷基,R3为氢或C1-4烷基,R4为氢或C1-4烷基。
进一步地,在上述技术方案中,所述有机溶剂为六氟异丙醇、2,2,2-三氟乙醇或N,N-二甲基甲酰胺。
进一步地,在上述技术方案中,所述添加剂为六氟锑酸银、双三氟甲烷磺酰亚胺银盐、醋酸银或醋酸钠。
进一步地,在上述技术方案中,所述钌催化剂为二氯双(4-甲基异丙基苯基)钌(II)([Ru(p-cymene)Cl2]2),所述铑催化剂为二(六氟锑酸)三乙腈(五甲基环戊二烯基)铑(III)([RhCp*(MeCN)3](SbF6)2)。
进一步地,在上述技术方案中,所述芳基偶氮甲碱亚胺1、4-乙烯基-1,3-二氧环戊-2-酮2、钌或铑催化剂与添加剂摩尔比为1-2:1-2:0.01-0.05:0.1-0.2。
进一步地,在上述技术方案中,所述反应温度为80-120℃。
进一步地,在上述技术方案中,所述反应在空气氛围下进行。
发明有益效果:
本发明与现有技术相比具有以下优点:(1)合成过程简单、高效,通过芳基偶氮甲碱亚胺直接与乙烯基环状碳酸酯的串联反应,即可高效合成茚并吡唑类化合物,具有原子经济性高的特点;(2)原料价廉易得;(3)操作简便;(4)底物适用范围广、官能团耐受性好。
附图说明
图1为实施例3中化合物3p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
向15mL反应管中依次加入化合物1a、2、催化剂、添加剂和溶剂,在空气条件下将反应管密封,并置于加热模块中升温搅拌反应。待反应结束后,冷却至室温,抽滤,滤液浓缩,过硅胶柱分离(石油醚/乙酸乙酯=1/1)得黄色油状产物3a。
通过改变反应的溶剂、催化剂、添加剂、温度和物料比等反应条件,得到一系列的结果,见表1。
表1不同条件下3a的合成a
实施例2
向15mL反应管中依次加入1a(40.4mg,0.2mmol)、2(34.2mg,0.3mmol)、[RhCp*(MeCN)3](SbF6)2(8.3mg,0.01mmol)、AgSbF6(6.9mg,0.02mmol)和2,2,2-三氟乙醇(2mL),然后将反应管密封,并置于120℃油浴中反应6h。反应结束后,将反应体系冷却至室温,抽滤,滤液浓缩,过硅胶柱分离(石油醚/乙酸乙酯=1/1)得到黄色油状产物3a(44.7mg,82%)。1HNMR(600MHz,CDCl3):δ7.29-7.25(m,3H),7.22-7.21(m,1H),5.55(br s,1H),4.62(d,J=8.4Hz,1H),3.99(d,J=12.0Hz,1H),3.88(dd,J1=12.0Hz,J2=8.4Hz,1H),3.23(t,J=9.0Hz,1H),3.10(dd,J1=16.8Hz,J2=7.8Hz,1H),2.85-2.79(m,3H),2.37(d,J=15.6Hz,1H),1.50(s,3H),1.27(s,3H).13C{1H}NMR(150MHz,CDCl3):δ164.9,142.5,140.3,128.4,127.6,125.5,125.3,64.0,63.75,63.69,61.6,49.7,46.8,34.3,26.3,19.6.HRMS(ESI)m/z:[M+H]+Calcd for C16H21N2O2 273.1598;Found 273.1590.
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,可以合成出一系列茚并吡唑类化合物3,具体结果如下:
a反应条件:1(0.2mmol),2(0.3mmol),[RhCp*(MeCN)3](SbF6)2(5mol%),六氟锑酸银(0.02mmol),2,2,2-三氟乙醇(2mL),120℃,6h,空气氛围;b分离收率。
代表性产物表征数据如下:10-(Hydroxymethyl)-3,3,7-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3b)
1H NMR(600MHz,CDCl3):δ7.11(d,J=7.8Hz,1H),7.08(d,J=7.8Hz,1H),7.06(s,1H),5.55(dd,J1=11.4Hz,J2=3.6Hz,1H),4.61(d,J=8.4Hz,1H),4.03-3.99(m,1H),3.92-3.88(m,1H),3.25(t,J=9.0Hz,1H),3.07(dd,J1=16.2Hz,J2=7.2Hz,1H),2.86-2.81(m,2H),2.77(d,J=16.2Hz,1H),2.40(d,J=15.0Hz,1H),2.36(s,3H),1.54(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.0,140.7,138.6,128.6,126.1,125.0,64.1,63.8,61.6,49.6,47.2,34.3,26.2,21.3,19.9.HRMS(ESI)m/z:[M+H]+Calcd for C17H23N2O2287.1754;Found 287.1750.
7-(tert-Butyl)-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3c)
1H NMR(600MHz,CDCl3):δ7.33(dd,J1=8.4Hz,J2=1.8Hz,1H),7.25(s,1H),7.20(d,J=7.8Hz,1H),5.56(dd,J1=11.4Hz,J2=3.6Hz,1H),4.62(d,J=8.4Hz,1H),4.01(td,J1=12.6Hz,J2=2.4Hz,1H),3.92-3.88(m,1H),3.29(t,J=8.4Hz,1H),3.11(dd,J1=16.2Hz,J2=7.2Hz,1H),2.88-2.81(m,3H),2.39(d,J=15.6Hz,1H),1.51(s,3H),1.30(s,9H),1.29(s,3H).13C{1H}NMR(150MHz,CDCl3):δ164.8,151.9,140.3,139.5,125.1,124.7,122.2,63.8,63.7,63.6,61.8,49.8,47.1,34.7,34.5,31.5,26.4,19.7.HRMS(ESI)m/z:[M+H]+Calcd for C20H29N2O2 329.2224;Found 329.2215.
10-(Hydroxymethyl)-7-methoxy-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3d)
1H NMR(600MHz,CDCl3):δ7.16(d,J=8.4Hz,1H),6.83(dd,J1=8.4Hz,J2=2.4Hz,1H),6.74(d,J=1.8Hz,1H),5.57(br s,1H),4.59(d,J=8.4Hz,1H),4.00(dd,J1=12.0Hz,J2=2.4Hz,1H),3.89(dd,J1=12.6Hz,J2=8.4Hz,1H),3.79(s,3H),3.29(t,J=9.0Hz,1H),3.09(dd,J1=16.2Hz,J2=7.2Hz,1H),2.87-2.78(m,3H),2.39(d,J=15.0Hz,1H),1.50(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ164.9,160.3,142.1,134.4,126.0,114.3,110.1,63.8,63.6,63.5,61.8,55.5,49.7,47.5,34.6,26.4,19.8.HRMS(ESI)m/z:[M+H]+Calcd for C17H23N2O3 303.1703;Found 303.1704.
7-Fluoro-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3e)
1H NMR(400MHz,CDCl3):δ7.21(dd,J1=8.0Hz,J2=5.2Hz,1H),6.98(td,J1=8.8Hz,J2=2.0Hz,1H),6.91(d,J=8.8Hz,1H),5.47(dd,J1=10.8Hz,J2=3.6Hz,1H),4.60(d,J=8.0Hz,1H),4.05-3.98(m,1H),3.92-3.86(m,1H),3.27(t,J=8.8Hz,1H),3.12(dd,J1=16.4Hz,J2=7.2Hz,1H),2.92-2.88(m,1H),2.85-2.79(m,2H),2.39(d,J=15.2Hz,1H),1.50(s,3H),1.28(s,3H).13C{1H}NMR(100MHz,CDCl3):δ165.0,163.3(d,1JC-F=244.1Hz),142.6(d,3JC-F=8.7Hz),138.1(d,4JC-F=2.9Hz),126.6(d,3JC-F=9.4Hz),115.0(d,2JC-F=23.1Hz),112.2(d,2JC-F=22.4Hz),63.8,63.7,63.3,61.5,49.6,47.3,34.3(d,4JC-F=2.1Hz),26.3,19.7.19F NMR(565MHz,CDCl3):δ-114.30--114.34(m).HRMS(ESI)m/z:[M+H]+Calcd for C16H20FN2O2 291.1503;Found 291.1503.
7-Chloro-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3f)
1H NMR(600MHz,CDCl3):δ7.25(dd,J1=8.4Hz,J2=1.8Hz,1H),7.21(s,1H),7.18(d,J=7.8Hz,1H),5.47-5.45(m,1H),4.59(d,J=7.8Hz,1H),4.01(t,J=10.2Hz,1H),3.88(dd,J1=12.6Hz,J2=8.4Hz,1H),3.24(t,J=9.0Hz,1H),3.10(dd,J1=16.2Hz,J2=7.2Hz,1H),2.87(dd,J1=15.6Hz,J2=7.8Hz,1H),2.83-2.78(m,2H),2.39(d,J=15.6Hz,1H),1.49(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.0,142.3,141.1,134.3,128.0,126.5,125.6,63.7,63.6,63.4,61.5,49.6,47.0,34.1,26.3,19.7.HRMS(ESI)m/z:[M+H]+Calcd for C16H20ClN2O2 307.1208;Found 307.1204.
7-Bromo-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3g)
1H NMR(600MHz,CDCl3):δ7.40(d,J=7.8Hz,1H),7.38(s,1H),7.13(d,J=7.8Hz,1H),5.44(dd,J1=10.8Hz,J2=3.6Hz,1H),4.57(d,J=8.4Hz,1H),4.03-3.99(m,1H),3.90-3.86(m,1H),3.24(t,J=9.0Hz,1H),3.12(dd,J1=16.8Hz,J2=7.2Hz,1H),2.88-2.79(m,3H),2.39(d,J=15.0Hz,1H),1.49(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,DMSO-d6):δ164.5,144.9,142.9,130.2,128.5,128.0,121.4,63.3,63.0,62.3,60.0,49.8,48.7,35.0,26.3,19.7.HRMS(ESI)m/z:[M+Na]+Calcd for C16H19BrN2NaO2 373.0522;Found 373.0512.
10-(Hydroxymethyl)-3,3-dimethyl-7-(trifluoromethyl)-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3h)
1H NMR(600MHz,CDCl3):δ7.55(d,J=7.8Hz,1H),7.50(s,1H),7.38(d,J=7.8Hz,1H),5.38-5.37(m,1H),4.67(d,J=8.4Hz,1H),4.04(t,J=10.8Hz,1H),3.92-3.89(m,1H),3.23(t,J=9.0Hz,1H),3.18(dd,J1=16.2Hz,J2=7.2Hz,1H),2.93(dd,J1=16.2Hz,J2=8.4Hz,1H),2.88(d,J=16.8Hz,1H),2.84(d,J=15.6Hz,1H),2.41(d,J=15.6Hz,1H),1.53(s,3H),1.30(s,3H).13C{1H}NMR(150MHz,CDCl3):165.0,146.5,141.1,131.0(q,2JC-F=32.9Hz),125.9,124.9(q,3JC-F=4.4Hz),124.1(q,1JC-F=271.4Hz),122.5(q,3JC-F=4.4Hz),63.9,63.8,63.5,61.3,49.5,46.8,34.1,26.4,19.7.19F NMR(565MHz,CDCl3):δ-62.24(s).HRMS(ESI)m/z:[M+H]+Calcd for C17H20F3N2O2 341.1471;Found 341.1467.
10-(Hydroxymethyl)-3,3,6-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3i)
1H NMR(600MHz,CDCl3):δ7.15(d,J=7.8Hz,1H),7.09(d,J=8.4Hz,1H),7.04(s,1H),5.60(dd,J1=10.8Hz,J2=3.6Hz,1H),4.60(d,J=8.4Hz,1H),4.02-3.98(m,1H),3.91-3.87(m,1H),3.28(t,J=9.0Hz,1H),3.08(dd,J1=16.2Hz,J2=7.2Hz,1H),2.86-2.82(m,2H),2.78(d,J=16.8Hz,1H),2.39(d,J=15.0Hz,1H),2.34(s,3H),1.51(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.0,142.5,137.5,137.2,129.5,125.7,125.3,64.0,63.9,63.8,61.6,49.6,47.0,33.8,26.3,21.4,19.7.HRMS(ESI)m/z:[M+H]+Calcd forC17H23N2O2 287.1754;Found 287.1749.
6-Chloro-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3j)
1H NMR(400MHz,CDCl3):δ7.25-7.22(m,2H),7.15(d,J=8.0Hz,1H),5.42(dd,J1=10.8Hz,J2=4.0Hz,1H),4.61(d,J=8.4Hz,1H),4.05-3.99(m,1H),3.92-3.86(m,1H),3.23(t,J=9.2Hz,1H),3.08(dd,J1=16.4Hz,J2=7.2Hz,1H),2.90-2.82(m,2H),2.78(d,J=16.8Hz,1H),2.39(d,J=15.2Hz,1H),1.52(s,3H),1.27(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.1,144.6,138.6,133.4,128.8,126.6,125.6,63.9,63.8,63.7,61.4,49.6,47.0,33.7,26.3,19.6.HRMS(ESI)m/z:[M+H]+Calcd for C16H20ClN2O2 307.1208;Found307.1206.
6-Bromo-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3k)
1H NMR(600MHz,CDCl3):δ7.38(dd,J1=8.4Hz,J2=1.8Hz,1H),7.37(s,1H),7.10(d,J=7.8Hz,1H),5.42(dd,J1=10.8Hz,J2=3.6Hz,1H),4.62(d,J=8.4Hz,1H),4.04-3.00(m,1H),3.91-3.87(m,1H),3.23(t,J=9.0Hz,1H),3.06(dd,J1=16.8Hz,J2=7.2Hz,1H),2.87-2.82(m,2H),2.76(d,J=16.8Hz,1H),2.39(d,J=15.6Hz,1H),1.52(s,3H),1.27(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.1,145.0,139.2,131.6,128.6,127.0,121.4,63.9,63.8,63.7,61.4,49.5,46.9,33.7,26.4,19.6.HRMS(ESI)m/z:[M+H]+Calcd forC16H20BrN2O2 351.0703;Found 351.0701.10-(Hydroxymethyl)-6-methoxy-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3l)
1H NMR(600MHz,CDCl3):δ7.13(d,J=7.8Hz,1H),6.83(dd,J1=8.4Hz,J2=1.8Hz,1H),6.78(d,J=1.8Hz,1H),5.52-5.50(m,1H),4.60(d,J=7.8Hz,1H),4.01(t,J=10.8Hz,1H),3.91-3.88(m,1H),3.81(s,3H),3.26(t,J=9.6Hz,1H),3.05(dd,J1=15.6Hz,J2=7.2Hz,1H),2.86-2.82(m,2H),2.74(d,J=16.2Hz,1H),2.39(d,J=15.0Hz,1H),1.52(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ164.9,159.7,144.0,132.1,126.2,114.7,110.3,64.1,63.8,63.7,61.7,55.5,49.7,47.3,33.4,26.4,19.6.HRMS(ESI)m/z:[M+H]+Calcd for C17H23N2O3 303.1703;Found 303.1696.
10-(Hydroxymethyl)-8-methoxy-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3m)
1H NMR(600MHz,CDCl3):δ7.28-7.26(m,1H),6.87(d,J=7.2Hz,1H),6.76(d,J=7.8Hz,1H),5.50(br s,1H),4.64(d,J=8.4Hz,1H),4.03-4.01(m,1H),3.89(dd,J1=12.6Hz,J2=8.4Hz,1H),3.83(s,3H),3.26(t,J=9.0Hz,1H),2.97(dd,J1=16.2Hz,J2=6.6Hz,1H),2.88-2.82(m,3H),2.39(d,J=15.0Hz,1H),1.51(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ164.9,156.5,144.3,129.4,128.3,117.1,109.4,64.5,63.9,63.7,61.6,55.3,49.7,46.7,31.1,26.4,19.6.HRMS(ESI)m/z:[M+H]+Calcd for C17H23N2O3303.1703;Found 303.1702.
6-Fluoro-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3n)
1H NMR(600MHz,CDCl3):δ7.17(dd,J1=7.8Hz,J2=4.8Hz,1H),6.98-6.94(m,2H),5.44(dd,J1=10.8Hz,J2=3.6Hz,1H),4.61(d,J=8.4Hz,1H),4.04-4.00(m,1H),3.92-3.88(m,1H),3.25(t,J=9.0Hz,1H),3.08(dd,J1=15.6Hz,J2=7.2Hz,1H),2.90-2.83(m,2H),2.77(d,J=16.2Hz,1H),2.40(d,J=15.6Hz,1H),1.51(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.0,162.8(d,1JC-F=243.9Hz),144.8(d,3JC-F=7.7Hz),135.5(d,4JC-F=2.3Hz),126.6(d,3JC-F=7.7Hz),115.8(d,2JC-F=23.0Hz),112.2(d,2JC-F=23.0Hz),63.9,63.8,63.7,61.5,49.6,47.3,33.5,26.3,19.6.19F NMR(565MHz,CDCl3):δ-115.2--115.3(m).HRMS(ESI)m/z:[M+H]+Calcd for C16H20FN2O2 291.1503;Found 291.1500.
8-Fluoro-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3o)
1H NMR(600MHz,CDCl3):δ7.29-7.27(m,1H),7.06(d,J=7.8Hz,1H),6.96(t,J=9.0Hz,1H),5.42(dd,J1=10.8Hz,J2=3.6Hz,1H),4.66(d,J=7.8Hz,1H),4.06-4.02(m,1H),3.92-3.88(m,1H),3.26(t,J=8.4Hz,1H),3.08(dd,J1=16.8Hz,J2=7.2Hz,1H),2.93-2.90(m,2H),2.83(d,J=15.6Hz,1H),2.40(d,J=15.6Hz,1H),1.51(s,3H),1.29(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.0,159.7(d,1JC-F=247.2Hz),146.1(d,3JC-F=5.6Hz),129.8(d,3JC-F=7.8Hz),126.8(d,2JC-F=17.6Hz),120.9(d,4JC-F=3.3Hz),114.7(d,2JC-F=20.7Hz),64.2(d,4JC-F=2.1Hz),63.8,63.6,61.4,49.6,46.8,30.3,26.4,19.7.19F NMR(565MHz,CDCl3):δ-117.50--117.53(m).HRMS(ESI)m/z:[M+H]+Calcd for C16H20FN2O2291.1503;Found291.1504.
10-(Hydroxymethyl)-3,3,5-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3p)
1H NMR(400MHz,CDCl3):δ7.15(t,J=7.6Hz,1H),7.04(d,J=7.2Hz,1H),7.00(d,J=7.6Hz,1H),5.30(dd,J1=10.4Hz,J2=3.6Hz,1H),4.70(d,J=7.2Hz,1H),4.08-4.01(m,1H),3.96-3.90(m,1H),3.22(t,J=8.8Hz,1H),3.01(dd,J1=16.0Hz,J2=6.8Hz,1H),2.84(d,J=15.2Hz,1H),2.78-2.74(m,2H),2.48(s,3H),2.27(d,J=14.8Hz,1H),1.52(s,3H),1.25(s,3H).13C{1H}NMR(100MHz,CDCl3):δ167.1,140.6,139.6,136.1,129.4,128.7,123.2,66.8,65.2,64.3,61.6,49.5,46.7,33.5,26.5,19.9,19.3.HRMS(ESI)m/z:[M+H]+Calcd for C17H23N2O2 287.1754;Found287.1746.
5-Fluoro-10-(hydroxymethyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3q)
1H NMR(400MHz,CDCl3):δ7.28-7.23(m,1H),7.01(d,J=7.2Hz,1H),6.92(t,J=8.4Hz,1H),5.49(br s,1H),4.80(d,J=8.0Hz,1H),4.01(dd,J1=12.4Hz,J2=2.4Hz,1H),3.90(dd,J1=12.4Hz,J2=8.0Hz,1H),3.39(t,J=8.4Hz,1H),3.12(dd,J1=16.8Hz,J2=8.0Hz,1H),2.95-2.89(m,2H),2.86(d,J=16.0Hz,1H),2.39(d,J=15.2Hz,1H),1.47(d,J=2.0Hz,3H),1.32(s,3H).13C{1H}NMR(150MHz,CDCl3):δ164.9,160.1(d,1JC-F=248.3Hz),144.6(d,3JC-F=5.4Hz),130.8(d,3JC-F=7.8Hz),128.4(d,2JC-F=14.3Hz),121.2(d,4JC-F=3.3Hz),114.3(d,2JC-F=20.7Hz),64.4,63.2,62.1(d,4JC-F=2.3Hz),62.0,50.0,47.9,35.1,25.8(d,3JC-F=5.4Hz),19.6.19F NMR(565MHz,CDCl3):δ-116.08--116.11(m).HRMS(ESI)m/z:[M+H]+Calcd for C16H20FN2O2 291.1503;Found 291.1502.
10-(Hydroxymethyl)-3,3,6,7-tetramethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3r)
1H NMR(600MHz,CDCl3):δ7.01(s,1H),7.00(s,1H),5.56(dd,J1=10.8Hz,J2=3.0Hz,1H),4.59(d,J=8.4Hz,1H),4.02-3.98(m,1H),3.91-3.87(m,1H),3.25(t,J=9.0Hz,1H),3.05(dd,J1=16.2Hz,J2=7.2Hz,1H),2.84-2.81(m,2H),2.74(d,J=16.2Hz,1H),2.39(d,J=15.6Hz,1H),2.26(s,3H),2.24(s,3H),1.53(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ164.9,140.0,137.8,137.1,136.2,126.4,126.0,63.91,63.89,63.7,61.8,49.7,47.1,34.0,26.4,19.94,19.88,19.7.HRMS(ESI)m/z:[M+H]+Calcd forC18H25N2O2 301.1911;Found 301.1903.
7-Fluoro-10-(hydroxymethyl)-3,3,6-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3s)
1H NMR(600MHz,CDCl3):δ7.04(d,J=7.2Hz,1H),6.86(d,J=9.6Hz,1H),5.46(dd,J1=10.8Hz,J2=3.0Hz,1H),4.58(d,J=7.8Hz,1H),4.03-3.99(m,1H),3.91-3.87(m,1H),3.25(t,J=9.0Hz,1H),3.07(dd,J1=16.2Hz,J2=7.2Hz,1H),2.88-2.83(m,2H),2.76(d,J=16.2Hz,1H),2.39(d,J=15.0Hz,1H),2.27(s,3H),1.52(s,3H),1.28(s,3H).13C{1H}NMR(150MHz,CDCl3):δ165.0,161.7(d,1JC-F=243.9Hz),139.5(d,3JC-F=8.7Hz),137.8(d,4JC-F=2.3Hz),127.7(d,3JC-F=5.4Hz),124.6(d,2JC-F=18.5Hz),111.8(d,2JC-F=23.1Hz),63.81,63.78,63.5,61.5,49.6,47.3,34.0(d,4JC-F=2.3Hz),26.4,19.7,14.8(d,3JC-F=4.4Hz).19F NMR(565MHz,CDCl3):δ-117.93--117.96(m).HRMS(ESI)m/z:[M+H]+CalcdforC17H22FN2O2 305.1660;Found 305.1655.
10-(Hydroxymethyl)-3-methyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3t)
1H NMR(600MHz,CDCl3):δ7.32-7.30(m,1H),7.29-7.27(m,2H),7.25-7.23(m,1H),5.43-5.41(m,1H),4.34(d,J=8.4Hz,1H),4.04-4.00(m,1H),3.93-3.90(m,1H),3.46-3.41(m,1H),3.39-3.35(m,1H),3.15(dd,J1=16.2Hz,J2=7.8Hz,1H),3.06-3.01(m,1H),2.89(dd,J1=16.8Hz,J2=2.4Hz,1H),2.74(dd,J1=15.6Hz,J2=7.2Hz,1H),2.65-2.60(m,1H),1.50(d,J=6.0Hz,3H).13C{1H}NMR(150MHz,CDCl3):164.8,141.3,141.2,128.8,127.6,125.6,125.4,73.4,64.3,63.2,61.6,46.8,43.2,34.8,18.7.HRMS(ESI)m/z:[M+H]+Calcdfor C15H19N2O2 259.1441;Found259.1437.
10-(Hydroxymethyl)-3-propyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3u)
1H NMR(600MHz,CDCl3):δ7.31-7.28(m,3H),7.24-7.23(m,1H),5.38(dd,J1=10.2Hz,J2=3.6Hz,1H),4.36(d,J=9.0Hz,1H),4.05-4.01(m,1H),3.93-3.89(m,1H),3.37-3.32(m,2H),3.14(dd,J1=16.2Hz,J2=7.8Hz,1H),3.04-3.00(m,1H),2.87(d,J=16.2Hz,1H),2.73(dd,J1=16.2Hz,J2=7.2Hz,1H),2.63-2.58(m,1H),1.96-1.90(m,1H),1.76-1.70(m,1H),1.49-1.37(m,2H),1.03(t,J=7.2Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ165.0,141.4,141.2,128.8,127.6,125.6,125.4,73.5,67.6,64.1,61.5,46.6,41.0,35.7,34.6,19.2,14.2.HRMS(ESI)m/z:[M+H]+Calcd for C17H23N2O2 287.1754;Found 287.1753.
10-(Hydroxymethyl)-2,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3v)
1H NMR(600MHz,CDCl3):δ7.33-7.32(m,1H),7.29-7.28(m,2H),7.25-7.23(m,1H),5.47(dd,J1=10.8Hz,J2=4.2Hz,1H),4.32(d,J=8.4Hz,1H),4.05-4.01(m,1H),3.91-3.87(m,1H),3.38(t,J=8.4Hz,1H),3.15(dd,J1=16.8Hz,J2=8.4Hz,1H),3.04-3.00(m,1H),2.93-2.88(m,2H),2.60-2.57(m,1H),1.50(d,J=6.0Hz,3H),1.22(d,J=6.6Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ167.1,141.3,141.2,128.8,127.6,125.6,125.5,73.3,70.6,64.2,61.6,47.8,46.6,34.7,17.3,12.1.HRMS(ESI)m/z:[M+H]+Calcd for C16H21N2O2273.1598;Found 273.1589.
实施例4
本发明所合成的产物茚并吡唑类化合物3a可以进行一系列反应,从而合成进一步的衍生物。例如:
在50mL两颈瓶中,加入3a(54.4mg,0.2mmol)和甲苯(10mL),氩气条件下向所得溶液中加入碘(103mg,0.4mmol)、三苯基膦(157mg,0.6mmol)和咪唑(40mg,0.6mmol),然后将体系在110℃反应6小时。待反应结束并冷却至室温后,减压浓缩。残留物过硅胶柱分离(石油醚/乙酸乙酯=1/1),得到白色固体产物4(62.8mg,82%)。1H NMR(600MHz,CDCl3):δ7.28-7.25(m,2H),7.23-7.21(m,2H),4.60(d,J=7.8Hz,1H),3.89(dd,J1=10.2Hz,J2=6.6Hz,1H),3.82(dd,J1=10.8Hz,J2=3.0Hz,1H),3.49-3.48(m,1H),3.31-3.29(m,1H),3.22(dd,J1=16.2Hz,J2=8.4Hz,1H),3.10(dd,J1=15.6Hz,J2=6.0Hz,1H),2.72(d,J=16.2Hz,1H),2.39(d,J=15.6Hz,1H),1.48(s,3H),1.34(s,3H).13C{1H}NMR(150MHz,CDCl3):δ163.7,142.5,141.0,128.6,127.1,125.5,125.3,62.9,61.4,57.7,55.6,50.8,36.7,26.9,20.9,7.0.
向15mL反应管中依次加入3a(54.4mg,0.2mmol)、DCC(41.3mg,0.2mmol)、DMAP(4.9mg,0.04mmol)、奥沙普秦(58.7mg,0.2mmol)和DCM(1mL),随后将体系在室温下反应24小时。反应结束后,通过硅藻土过滤,滤液减压浓缩,过硅胶柱分离(石油醚/乙酸乙酯=1/1),得到白色固体产物5(77.8mg,71%)。1H NMR(600MHz,CDCl3):δ7.57(d,J=6.6Hz,2H),7.54(d,J=7.2Hz,2H),7.33-7.26(m,6H),7.23-7.21(m,3H),7.15(d,J=5.4Hz,1H),4.88(dd,J1=11.4Hz,J2=4.2Hz,1H),4.72(dd,J1=11.4Hz,J2=3.0Hz,1H),4.42(d,J=7.8Hz,1H),3.49-3.48(m,1H),3.26-3.16(m,3H),3.03-2.94(m,3H),2.88(dd,J1=16.2Hz,J2=3.6Hz,1H),2.74(d,J=15.6Hz,1H),2.31(d,J=15.0Hz,1H),1.37(s,3H),1.32(s,3H).13C{1H}NMR(150MHz,CDCl3):δ171.7,164.3,161.7,145.5,142.0,141.3,135.2,132.5,128.9,128.7,128.55,128.51,128.4,128.1,127.9,127.3,126.4,125.4,63.5,62.6,60.6,57.9,50.4,49.2,35.4,31.0,26.5,23.4,19.9.
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 (7)
2.根据权利要求1所述茚并吡唑类化合物的合成方法,其特征在于:所述有机溶剂为六氟异丙醇、2,2,2-三氟乙醇或N,N-二甲基甲酰胺。
3.根据权利要求1所述茚并吡唑类化合物的合成方法,其特征在于:所述添加剂为六氟锑酸银、双三氟甲烷磺酰亚胺银盐、醋酸银或醋酸钠。
4.根据权利要求1所述茚并吡唑类化合物的合成方法,其特征在于:所述钌催化剂为[Ru(p-cymene)Cl2]2,所述铑催化剂为[RhCp*(MeCN)3](SbF6)2。
5.根据权利要求1所述茚并吡唑类化合物的合成方法,其特征在于:所述芳基偶氮甲碱亚胺1、4-乙烯基-1,3-二氧环戊-2-酮2、钌或铑催化剂与添加剂摩尔比为1-2:1-2:0.01-0.05:0.1-0.2。
6.根据权利要求1所述茚并吡唑类化合物的合成方法,其特征在于:反应温度为80-120℃。
7.根据权利要求1-6任意一项所述茚并吡唑类化合物的合成方法,其特征在于:反应在空气氛围下进行。
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Non-Patent Citations (3)
Title |
---|
HEEYOUNG LEE等: "Allylic Acetals as Acrolein Oxonium Precursors in Tandem C@H Allylation and [3+2] Dipolar Cycloaddition", ANGEW. CHEM. INT. ED., pages 9470 - 9474 * |
MAN ZHU,: "Regio- and stereo-selective construction of cis-indeno[1, 2-c]isoxazoles via a C–H allylation/1, 3-dipolar cycloaddition cascade", ORG. CHEM. FRONT., pages 5879 - 5884 * |
WU, MIN等: "Enantioselective synthesis of indenopyrazolopyrazolones enabled by dual directing groups-assisted and rhodium(III)-catalyzed tandem C-H alkenylation/[3 + 2] stepwise cycloaddition", CHINESE CHEMICAL LETTERS, pages 842 - 846 * |
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