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CN111675712B - 一种吡唑啉酮并苯二氮杂卓类化合物的合成方法 - Google Patents

一种吡唑啉酮并苯二氮杂卓类化合物的合成方法 Download PDF

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CN111675712B
CN111675712B CN202010578323.4A CN202010578323A CN111675712B CN 111675712 B CN111675712 B CN 111675712B CN 202010578323 A CN202010578323 A CN 202010578323A CN 111675712 B CN111675712 B CN 111675712B
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CN111675712A (zh
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张新迎
张凌华
李露露
辛茜茜
徐园双
范学森
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Henan Normal University
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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Abstract

本发明公开了一种吡唑啉酮并苯二氮杂卓类化合物的合成方法，属于有机合成技术领域。以1‑芳基吡唑烷酮类化合物1和炔丙醇类化合物2为原料，在[RhCp*Cl2]2或RhCp*(OAc)2等铑催化剂和醋酸锌/醋酸钠等添加剂存在下，有机溶剂中反应得到吡唑啉酮并苯二氮杂卓类化合物3。本发明通过1‑芳基吡唑烷酮类化合物和炔丙醇类化合物之间的[4+3]环化反应，高效地、区域选择性地合成了吡唑啉酮并苯二氮杂卓类化合物，该方法具有原料简单易得、操作简便、条件温和、选择性好及底物适用范围广等优点，具有潜在的工业应用前景。

Description

一种吡唑啉酮并苯二氮杂卓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，具体涉及一种吡唑啉酮并苯二氮杂卓类化合物的合成方法。
背景技术
吡唑啉酮并苯二氮杂卓是一类重要的含氮稠杂环类化合物，该类化合物不仅在自然界中广泛存在，而且许多都具有抗菌、抗癌、抗病毒、抗焦虑和神经保护等独特的生物及药物活性。
目前，尽管现有文献中已经报道了合成吡唑啉酮并苯二氮杂卓类化合物的可靠方法，但这些方法仍然存在原料不易得到、合成步骤多、操作繁琐和原子经济性低等问题。
因此，研究并开发从简单易得的原料出发，经过简洁的操作来合成吡唑啉酮并苯二氮杂卓类化合物的新方法，具有十分重要的理论意义和实用前景。
发明内容
本发明解决的技术问题是提供了一种吡唑啉酮并苯二氮杂卓类化合物的合成方法，该合成方法通过1-芳基吡唑烷酮类化合物和炔丙醇类化合物之间的[4+3]环化反应，高效地、区域选择性地合成了吡唑啉酮并苯二氮杂卓类化合物，该方法具有原料简单易得、操作简便、条件温和、选择性好及底物适用范围广等优点，具有潜在的工业应用前景。
本发明为解决上述技术问题采用如下技术方案，一种吡唑啉酮并苯二氮杂卓类化合物的合成方法，包括如下操作：以1-芳基吡唑烷酮类化合物1和炔丙醇类化合物2为原料，在铑或钌催化剂和添加剂存在下，有机溶剂中反应得到吡唑啉酮并苯二氮杂卓类化合物3，反应方程式为：
Figure BDA0002551614660000021
其中：R1为氢、卤素、三氟甲基、氰基、硝基、C1-4烷基或C1-4烷氧基；R2为氢或C1-4烷基；R3为氢或C1-4烷基；R4为C1-6链状烷基、C3-6环烷基、噻吩基、吡啶基、苯基或取代苯基，取代苯基苯环上的取代基为卤素、三氟甲基、硝基、C1-4烷基或C1-4烷氧基；R5和R6各自独立为C1-4烷基、C3-6环烷基或共同组成C4-6环烷基。
进一步地，在上述技术方案中，所述反应溶剂选自1,2-二氯乙烷(DCE)、甲醇(CH3OH)、甲苯(toluene)、乙腈(CH3CN)、二氯甲烷(DCM)或丙酮(acetone)。
在实验过程中发现上述反应溶剂除起到溶解原料的作用外，对反应收率影响较大，其中甲苯、二氯乙烷、二氯甲烷和丙酮效果良好，甲苯反应结果最佳。
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{简称[RhCp*Cl2]2}、五甲基环戊二烯基醋酸铑(III){简称RhCp*(OAc)2}或[RhCl(COD)]2；所述钌催化剂为[Ru(p-cymene)Cl2]2。采用其它金属催化剂，例如CoCp*(CO)I2、MnBr(CO)5或[IrCp*Cl2]2等催化剂时，反应几乎不发生(收率低于5％)。
进一步地，在上述技术方案中，所述添加剂为醋酸锌、醋酸、醋酸钠、醋酸铯、醋酸钾中的一种或几种混合。优选情况下，添加剂为醋酸锌与醋酸、醋酸钠、醋酸铯、醋酸钾其中之一组成。为进一步降低成本和提高收率，最优选情况下，添加剂为醋酸锌和醋酸钠组合，两者摩尔比例最佳为1:1。
进一步地，在上述技术方案中，所述1-芳基吡唑啉酮类化合物1、炔丙醇类化合物2、添加剂和催化剂的投料摩尔比为1:1-1.5:0.5-1.0:0.02-0.03。
进一步地，在上述技术方案中，所述反应温度为80-110℃。
进一步地，在上述技术方案中，所得产物3可通过不同还原剂的作用得到不同的产物。例如采用钯碳催化氢化，将双键还原得到化合物4；采用四氢铝锂还原，将吡唑啉酮的酰胺键打开得到化合物5。
Figure BDA0002551614660000031
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1-芳基吡唑烷酮类化合物和炔丙醇类化合物之间的一锅串联反应，即可高选择性地合成出吡唑啉酮并苯二氮杂卓类化合物；2)原料价廉易得，反应条件温和，操作简便，底物的适用范围广；3)反应原子经济性高，符合绿色化学的要求。
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 BDA0002551614660000032
向15mL反应瓶中依次加入1a、2a、溶剂、催化剂和添加剂，盖上塞子密封，将其置于油浴中升温搅拌反应。待反应结束后，冷却至室温，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得白色固体产物3a。
通过改变反应的催化剂、添加剂、溶剂、反应物之间的当量比和反应温度等反应条件，得到一系列的结果，见表1。
表1不同反应条件下3a的合成a
Figure BDA0002551614660000041
实施例2
Figure BDA0002551614660000042
向15mL反应瓶中依次加入1a(48.7mg,0.3mmol)、2a(48.1mg,0.3mmol)、甲苯(2mL)、二氯(五甲基环戊二烯基)合铑(III)二聚体([RhCp*Cl2]2,4.7mg,0.0075mmol)、醋酸锌(27.5mg,0.15mmol)和醋酸钠(12.3mg,0.15mmol)，盖上塞子密封，将其置于100℃油浴中搅拌反应4h。待反应结束后，冷却至室温，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得白色固体产物3a(80.5mg,88％)。该化合物的表征数据为：1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.77(t,J＝7.2Hz,2H),4.10(t,J＝7.2Hz,2H),5.99(s,1H),6.99-7.01(m,1H),7.03-7.07(m,1H),7.18-7.20(m,2H),7.25-7.26(m,2H),7.28-7.33(m,3H).13C{1H}NMR(100MHz,CDCl3)δ26.9,33.3,49.0,63.1,116.3,124.4,127.4,127.9,128.1,129.3,132.1,132.6,136.5,139.9,144.4,149.6,173.6.HRMS calcd for C20H21N2O:305.1648[M+H]+,found:305.1647.
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2，可以合成出各种吡唑啉酮并苯二氮杂卓类化合物3a-3z和3aa-3ee，具体结果如下：
Figure BDA0002551614660000061
a反应条件:1(0.3mmol),2(0.3mmol),[RhCp*Cl2]2(0.0075mmol),Zn(OAc)2(0.15mmol),NaOAc(0.15mmol),toluene(2mL),100℃,4h；b分离收率。
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代表性产物表征数据如下：
5,5,9-Trimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3b)
White solid(80.4mg,84％).1H NMR(400MHz,CDCl3)δ1.66(s,6H),2.20(s,3H),2.77(t,J＝7.6Hz,2H),4.07(t,J＝7.6Hz,2H),5.99(s,1H),6.80(s,1H),7.06(d,J＝8.0Hz,1H),7.16(d,J＝8.0Hz,1H),7.19-7.21(m,2H),7.30-7.33(m,3H).13C{1H}NMR(150MHz,CDCl3)δ20.8,26.9,33.3,49.0,62.7,116.2,127.3,128.1,128.5,129.2,132.4,132.5,134.0,136.7,139.8,144.3,147.2,173.2.HRMS calcd for C21H23N2O:319.1805[M+H]+,found:319.1804.
9-Methoxy-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3c)
Light yellow solid(70.2mg,70％).1H NMR(400MHz,CDCl3)δ1.65(s,6H),2.77(t,J＝7.2Hz,2H),3.65(s,3H),4.06(t,J＝7.2Hz,2H),6.02(s,1H),6.54(d,J＝2.4Hz,1H),6.81(dd,J1＝9.2Hz,J2＝2.4Hz,1H),7.18-7.23(m,3H),7.30-7.33(m,3H).13C{1H}NMR(150MHz,CDCl3)δ26.8,33.4,49.1,55.4,62.6,113.1,117.2,117.3,127.5,128.2,129.2,134.0,136.7,140.1,143.1,143.9,156.2,172.9.HRMS calcd for C21H23N2O2:335.1754[M+H]+,found:335.1754.
9-Fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3d)
White solid(79.3mg,82％).1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.77(t,J＝7.2Hz,2H),4.08(t,J＝7.6Hz,2H),6.02(s,1H),6.71(dd,J1＝9.6Hz,J2＝2.8Hz,1H),6.95(td,J1＝8.4Hz,J2＝2.8Hz,1H),7.18-7.23(m,3H),7.32-7.35(m,3H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.2,49.4,63.1,114.3(d,2JC-F＝22.4Hz),117.5(d,3JC-F＝8.7Hz),118.4(d,2JC-F＝23.2Hz),127.6,128.3,129.2,134.6(d,3JC-F＝7.3Hz),135.6(d,4JC-F＝2.1Hz),141.0,143.7,145.8(d,4JC-F＝2.9Hz),159.4(d,1JC-F＝242.0Hz),173.5.19F NMR(376MHz,CDCl3)δ-118.14–-118.08(m).HRMS calcd for C20H20FN2O:323.1554[M+H]+,found:323.1553.
9-Chloro-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3e)
White solid(74.1mg,73％).1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.75(t,J＝7.2Hz,2H),4.07(t,J＝7.2Hz,2H),6.00(s,1H),6.97(d,J＝2.0Hz,1H),7.17-7.23(m,4H),7.32-7.36(m,3H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.1,49.2,63.3,117.5,127.6,127.7,128.4,129.2,129.8,131.7,134.3,135.3,141.2,143.8,148.2,173.6.HRMS calcdforC20H20ClN2O:339.1259[M+H]+,found:339.1242.
9-Bromo-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3f)
White solid(90.5mg,79％).1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.75(t,J＝7.2Hz,2H),4.07(t,J＝7.2Hz,2H),6.00(s,1H),7.11-7.14(m,2H),7.17-7.19(m,2H),7.33-7.38(m,4H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.1,49.2,63.3,117.5,117.9,127.7,128.4,129.2,130.5,134.60,134.63,135.2,141.3,143.7,148.7,173.6.HRMScalcd for C20H20BrN2O:383.0754[M+H]+,found:383.0751.
5,5-Dimethyl-7-phenyl-9-(trifluoromethyl)-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3g)
White solid(91.5mg,82％).1H NMR(400MHz,CDCl3)δ1.69(s,6H),2.77(t,J＝7.2Hz,2H),4.13(t,J＝7.2Hz,2H),6.03(s,1H),7.15-7.17(m,2H),7.26(s,1H),7.33-7.36(m,4H),7.51(d,J＝8.4Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ26.9,33.0,49.3,63.8,116.4,123.9(q,1JC-F＝270.1Hz),124.5(q,3JC-F＝3.6Hz),126.5(q,2JC-F＝32.5Hz),127.8,128.4,129.17,129,24(q,3JC-F＝3.6Hz),132.9,135.1,141.6,143.8,152.5,174.1.19F NMR(376MHz,CDCl3)δ-62.22(s).HRMS calcd for C21H20F3N2O:373.1522[M+H]+,found:373.1523.
5,5-Dimethyl-3-oxo-7-phenyl-2,3-dihydro-1H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepine-9-carbonitrile(3h)
Light yellow solid(77.4mg,78％).1H NMR(400MHz,CDCl3)δ1.69(s,6H),2.75(t,J＝7.2Hz,2H),4.13(t,J＝7.2Hz,2H),6.00(s,1H),7.12-7.15(m,2H),7.29(d,J＝1.2Hz,1H),7.31-7.36(m,4H),7.54(dd,J1＝8.4Hz,J2＝1.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ26.9,32.9,49.3,64.2,107.9,116.8,118.6,127.9,128.6,129.2,131.1,133.3,134.2,136.2,142.2,143.7,153.4,174.4.HRMS calcd for C21H20N3O:330.1601[M+H]+,found:330.1596.
11-Fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3i)
Light yelow solid(62.8mg,65％).1H NMR(400MHz,CDCl3)δ1.62(s,6H),2.85(t,J＝7.2Hz,2H),4.11(t,J＝7.2Hz,2H),6.11(s,1H),6.77-6.79(m,1H),7.00-7.04(m,2H),7.19-7.21(m,2H),7.30-7.33(m,3H).13C{1H}NMR(100MHz,CDCl3)δ26.7,35.0(d,5JC-F＝7.2Hz),51.6(d,4JC-F＝12.3Hz),62.4,116.3(d,2JC-F＝24.5Hz),125.5(d,3JC-F＝9.3Hz),127.1(d,3JC-F＝2.9Hz),127.6,128.2,129.0,136.1(d,2JC-F＝10.1Hz),137.0(d,4JC-F＝2.9Hz),137.2(d,4JC-F＝2.9Hz),140.4,143.9,153.9(d,1JC-F＝243.4Hz),174.0.19F NMR(376MHz,CDCl3)δ-119.91(dd,J1＝10.9Hz,J2＝5.6Hz).HRMS calcd for C20H20FN2O:323.1554[M+H]+,found:323.1551.
5,5,10-Trimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3j)
White solid(87.0mg,91％).1H NMR(400MHz,CDCl3)δ1.66(s,6H),2.39(s,3H),2.78(t,J＝7.6Hz,2H),4.09(t,J＝7.6Hz,2H),5.94(s,1H),6.88(s,2H),7.05(s,1H),7.18-7.20(m,2H),7.29-7.33(m,3H).13C{1H}NMR(100MHz,CDCl3)δ21.7,26.9,33.3,48.9,63.0,117.1,125.3,127.3,128.1,129.3,129.9,131.9,136.5,137.9,139.1,144.5,149.4,173.5.HRMS calcd forC21H23N2O:319.1805[M+H]+,found:319.1804.
10-Methoxy-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3k)
Brown syrup(75.1mg,75％).1H NMR(400MHz,CDCl3)δ1.66(s,6H),2.77(t,J＝7.2Hz,2H),3.82(s,3H),4.06(t,J＝7.2Hz,2H),5.86(s,1H),6.60(dd,J1＝8.4Hz,J2＝2.0Hz,1H),6.80(d,J＝2.4Hz,1H),6.92(d,J＝8.8Hz,1H),7.19-7.21(m,2H),7.28-7.32(m,3H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.4,49.1,55.4,62.6,113.1,117.2,117.3,127.5,128.2,129.2,134.0,136.7,140.1,143.1,143.9,156.2,172.9.HRMS calcd forC21H23N2O2:335.1754[M+H]+,found:335.1754.
10-Bromo-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3l)
Light yellow solid(99.7mg,87％).1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.77(t,J＝7.6Hz,2H),4.07(t,J＝7.6Hz,2H),5.97(s,1H),6.86(d,J＝8.4Hz,1H),7.16-7.19(m,3H),7.31-7.33(m,3H),7.38(s,1H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.1,49.2,63.3,117.5,127.6,127.7,128.4,129.2,129.8,131.7,134.3,135.3,141.2,143.8,148.2,173.6.HRMScalcd for C20H20BrN2O:383.0754[M+H]+,found:383.0748.
10-Fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3m)
White solid(34.8mg,36％).1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.77(t,J＝7.6Hz,2H),4.06(t,J＝7.6Hz,2H),5.93(s,1H),6.77(td,J1＝8.0Hz,J2＝2.4Hz,1H),6.95-6.98(m,2H),7.16-7.18(m,2H),7.30-7.33(m,3H).13C{1H}NMR(100MHz,CDCl3)δ26.9,32.9,49.2,63.4,104.1(d,2JC-F＝23.8Hz),111.3(d,2JC-F＝20.9Hz),127.5,128.2,128.6(d,4JC-F＝2.9Hz),129.2,133.6(d,3JC-F＝8.7Hz),135.5,139.5,144.3,151.2(d,3JC-F＝6.5Hz),161.7(d,1JC-F＝247.0Hz),173.6.19F NMR(376MHz,CDCl3)δ-112.09–-112.02(m).HRMScalcd forC20H20FN2O:323.1554[M+H]+,found:323.1555.
8-Fluoro-5,5-dimethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3m')
Light yellow solid(32.8mg,34％).1H NMR(400MHz,CDCl3)δ1.65(s,6H),2.75(brs,2H),4.07(t,J＝7.6Hz,2H),6.22(s,1H),6.84-6.89(m,1H),7.11(d,J＝8.0Hz,1H),7.14-7.17(m,2H),7.27-7.33(m,4H).13C{1H}NMR(150MHz,CDCl3)δ26.8,33.1,49.0,61.7,112.4(d,4JC-F＝3.3Hz),113.1(d,2JC-F＝21.9Hz),120.8(d,2JC-F＝12.0Hz),126.7,127.3,128.2,129.1(d,3JC-F＝9.9Hz),133.2,141.8,143.2(d,4JC-F＝2.3Hz),151.4(d,3JC-F＝5.4Hz),161.0(d,1JC-F＝250.5Hz),172.1.19F NMR(376MHz,CDCl3)δ-101.96(dd,J1＝9.8Hz,J2＝5.6Hz).HRMS calcd for C20H20FN2O:323.1554[M+H]+,found:323.1554.
2,2,5,5-Tetramethyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3n)
White solid(80.7mg,81％).1H NMR(600MHz,CDCl3)δ1.32(s,6H),1.68(s,6H),4.03(s,2H),5.93(s,1H),6.97-7.00(m,2H),7.16-7.18(m,2H),7.20-7.23(m,1H),7.28-7.32(m,3H),7.34(d,J＝7.8Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ24.7,26.8,42.4,59.8,63.8,117.2,123.5,127.0,127.2,128.1,129.4,131.9,132.4,136.4,139.8,145.0,149.7,180.4.HRMS calcdfor C22H25N2O:333.1961[M+H]+,found:333.1959.
5,5-Dimethyl-7-(p-tolyl)-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one
(3o)
White solid(83mg,87％).1H NMR(600MHz,CDCl3)δ1.66(s,6H),2.36(s,3H),2.77(t,J＝7.2Hz,2H),4.09(t,J＝7.2Hz,2H),5.98(s,1H),7.01-7.06(m,2H),7.08(d,J＝8.4Hz,2H),7.12(d,J＝7.8Hz,2H),7.24-7.25(m,2H).13C{1H}NMR(150MHz,CDCl3)δ21.2,26.9,33.3,49.0,63.0,116.3,124.4,127.8,128.8,129.2,132.1,132.8,136.4,137.1,139.4,141.6,149.5,173.5.HRMS calcd for C21H23N2O:319.1805[M+H]+,found:319.1807.
7-(4-Methoxyphenyl)-5,5-dimethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3p)
White solid(83.9mg,84％).1H NMR(600MHz,CDCl3)δ1.66(s,6H),2.77(t,J＝7.2Hz,2H),3.81(s,3H),4.09(t,J＝7.2Hz,2H),5.98(s,1H),6.83-6.85(m,2H),7.03-7.07(m,2H),7.10-7.13(m,2H),7.25-7.26(m,2H).13C{1H}NMR(150MHz,CDCl3)δ26.9,33.3,49.0,55.3,62.8,113.5,116.3,124.4,127.8,130.4,132.1,132.9,136.1,136.9,139.0,149.5,159.1,173.3.HRMS calcd for C21H23N2O2:335.1754[M+H]+,found:335.1760.
7-(4-Fluorophenyl)-5,5-dimethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3q)
White solid(71.5mg,74％).1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.77(t,J＝7.2Hz,2H),4.10(t,J＝7.2Hz,2H),5.97(s,1H),6.97-7.02(m,3H),7.04-7.08(m,1H),7.14-7.17(m,2H),7.25-7.27(m,2H).13C{1H}NMR(100MHz,CDCl3)δ26.9,33.2,49.0,63.0,115.0(d,2JC-F＝20.9Hz),116.3,124.5,128.0,130.8(d,3JC-F＝8.0Hz),132.0,132.4,135.5,139.9,140.4(d,4JC-F＝2.8Hz),149.6,162.3(d,1JC-F＝244.8Hz),173.5.19F NMR(376MHz,CDCl3)δ-115.13–-115.06(m).HRMS calcd for C20H20FN2O:323.1554[M+H]+,found:323.1557.
7-(4-Chlorophenyl)-5,5-dimethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3r)
White solid(84.2mg,83％).1H NMR(400MHz,CDCl3)δ1.66(s,6H),2.77(t,J＝7.2Hz,2H),4.10(t,J＝7.6Hz,2H),5.97(s,1H),6.97(d,J＝7.6Hz,1H),7.05-7.09(m,1H),7.13(d,J＝8.0Hz,2H),7.27-7.29(m,4H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.2,49.0,63.1,116.3,124.5,128.1,128.3,130.6,131.9,132.2,133.3,135.4,140.2,142.8,149.6,173.6.HRMS calcdforC20H20ClN2O:339.1259[M+H]+,found:339.1258.
7-(4-Bromophenyl)-5,5-dimethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3s)
White solid(91.7mg,80％).1H NMR(400MHz,CDCl3)δ1.66(s,6H),2.77(t,J＝7.6Hz,2H),4.10(t,J＝7.6Hz,2H),5.96(s,1H),6.97(d,J＝7.6Hz,1H),7.04-7.08(m,3H),7.26-7.30(m,2H),7.44(d,J＝8.0Hz,2H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.2,49.0,63.1,116.3,121.5,124.5,128.1,130.9,131.3,131.9,132.1,135.4,140.2,143.3,149.6,173.6.HRMS calcdfor C20H20BrN2O:383.0754[M+H]+,found:383.0760.
5,5-Dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3t)
White solid(90.4mg,81％).1H NMR(400MHz,CDCl3)δ1.68(s,6H),2.78(t,J＝7.2Hz,2H),4.12(t,J＝7.2Hz,2H),5.99(s,1H),6.93(d,J＝7.6Hz,1H),7.05-7.09(m,1H),7.27-7.32(m,4H),7.57(d,J＝8.0Hz,2H).13C{1H}NMR(100MHz,CDCl3)δ26.8,33.2,49.1,63.3,116.4,124.2(q,1JC-F＝270.8Hz),124.6,125.1(q,3JC-F＝3.6Hz),128.2,129.5(q,2JC-F＝31.8Hz),129.6,131.8,131.9,135.3,141.1,148.0,149.7,173.8.19F NMR(376MHz,CDCl3)δ-62.40(s).HRMS calcd for C21H20F3N2O:373.1522[M+H]+,found:373.1527.
5,5-Dimethyl-7-(4-nitrophenyl)-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3u)
Light yellow solid(68.1mg,65％).1H NMR(400MHz,CDCl3)δ1.70(s,6H),2.79(t,J＝7.2Hz,2H),4.12(t,J＝7.6Hz,2H),6.03(s,1H),6.89-6.91(m,1H),7.07-7.11(m,1H),7.29-7.32(m,2H),7.34-7.31(m,2H),8.16-8.19(m,2H).13C{1H}NMR(100MHz,CDCl3)δ26.7,33.2,49.1,63.4,116.5,123.5,124.7,128.5,130.0,131.4,131.8,134.7,141.9,147.1,149.8,151.0,173.8.HRMS calcd for C20H20N3O3:350.1499[M+H]+,found:350.1497.
5,5-Dimethyl-7-(o-tolyl)-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one
(3v)
White solid(85.9mg,90％).1H NMR(400MHz,CDCl3)δ1.69(s,6H),1.96(s,3H),2.76(brs,2H),4.11(t,J＝7.2Hz,2H),5.74(s,1H),6.79(d,J＝8.0Hz,1H),6.94-6.98(m,1H),7.13-7.16(m,2H),7.17-7.24(m,4H).13C{1H}NMR(100MHz,CDCl3)δ19.7,26.9,33.4,49.2,63.8,115.9,124.4,125.7,127.38,127.40,130.1,130.2,131.1,132.3,135.0,136.5,140.4,144.0,148.9,174.6.HRMS calcd for C21H23N2O:319.1805[M+H]+,found:319.1808.
7-(2-Bromophenyl)-5,5-dimethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3w)
White solid(99.7mg,87％).1H NMR(400MHz,CDCl3)δ1.71(s,6H),2.77(t,J＝7.2Hz,2H),4.13(t,J＝7.2Hz,2H),5.75(s,1H),6.77(d,J＝7.6Hz,1H),6.98-7.02(m,1H),7.16-7.31(m,5H),7.59(d,J＝8.0Hz,1H).13C{1H}NMR(150MHz,CDCl3)δ26.8,33.2,49.0,63.2,116.4,124.6,127.46,127.50,128.1,129.3,129.4,131.9,132.0,134.0,135.3,140.6,146.2,149.6,173.7.HRMS calcd for C20H20BrN2O:383.0754[M+H]+,found:383.0757.
5,5-Dimethyl-7-(m-tolyl)-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one
(3x)
White solid(78.3mg,82％).1H NMR(400MHz,CDCl3)δ1.67(s,6H),2.33(s,3H),2.77(t,J＝7.6Hz,2H),4.10(t,J＝7.2Hz,2H),5.98(s,1H),6.98-7.02(m,3H),7.04-7.08(m,1H),7.11(d,J＝7.6Hz,1H),7.20(t,J＝7.2Hz,1H),7.25-7.26(m,2H).13C{1H}NMR(150MHz,CDCl3)δ21.4,26.9,33.3,49.0,63.0,116.3,124.4,126.4,127.8,128.0,128.1,129.9,132.2,132.7,136.5,137.7,139.7,144.4,149.5,173.5.HRMS calcd for C21H23N2O:319.1805[M+H]+,found:319.1807.
7-(3-Chlorophenyl)-5,5-dimethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3y)
Light yellow solid(74.1mg,73％).1H NMR(400MHz,CDCl3)δ1.69(s,6H),2.77(t,J＝7.2Hz,2H),4.10(t,J＝7.2Hz,2H),5.97(s,1H),6.98(d,J＝8.0Hz,1H),7.06-7.10(m,2H),7.20(s,1H),7.22-7.28(m,4H).13C{1H}NMR(150MHz,CDCl3)δ26.8,33.2,49.0,63.2,116.4,124.6,127.46,127.50,128.1,129.3,129.4,131.9,132.0,134.0,135.3,140.6,146.2,149.6,173.7.HRMS calcd for C20H20ClN2O:339.1259[M+H]+,found:339.1258.
5,5-Dimethyl-7-(thiophen-2-yl)-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3z)
White solid(76.3mg,82％).1H NMR(400MHz,CDCl3)δ1.64(s,6H),2.76(t,J＝7.2Hz,2H),4.07(t,J＝7.2Hz,2H),6.26(s,1H),6.86(d,J＝3.6Hz,1H),6.97(t,J＝4.0Hz,1H),7.14(t,J＝7.6Hz,1H),7.22(d,J＝5.2Hz,1H),7.25-7.32(m,2H),7.37(d,J＝8.0Hz,1H).13C{1H}NMR(150MHz,CDCl3)δ26.7,33.2,48.8,62.3,116.6,124.7,124.9,126.7,127.0,128.4,130.3,131.7,132.2,139.4,146.7,149.2,172.8.HRMS calcd forC18H19N2OS:311.1213[M+H]+,found:311.1218.
7-Cyclopropyl-5,5-dimethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3aa)
White solid(70.8mg,88％).1H NMR(400MHz,CDCl3)δ0.61(q,J＝5.2Hz,2H),0.82-0.87(m,2H),1.54(s,6H),1.58-1.62(m,1H),2.73(t,J＝7.2Hz,2H),4.04(t,J＝7.2Hz,2H),5.66(s,1H),7.18-7.26(m,3H),7.90(d,J＝7.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ7.0,19.2,27.0,33.3,49.0,62.7,116.1,124.6,127.4,128.9,133.5,134.3,135.9,148.4,173.6.HRMScalcd for C17H21N2O:269.1648[M+H]+,found:269.1649.
5-Ethyl-5-methyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3bb)
White solid(77.3mg,81％).1H NMR(400MHz,CDCl3)δ0.86(t,J＝7.2Hz,3H),1.60(s,3H),1.63-1.72(m,1H),2.53-2.62(m,1H),2.68-2.75(m,1H),2.83-2.91(m,1H),4.03-4.10(m,1H),4.14-4.21(m,1H),5.92(s,1H),7.01(d,J＝7.6Hz,1H),7.04-7.08(m,1H),7.19-7.23(m,2H),7.26-7.27(m,2H),7.30-7.34(m,3H).13C{1H}NMR(100MHz,CDCl3)δ9.0,26.3,32.0,33.3,48.7,66.7,116.4,124.5,127.4,127.8,128.1,129.2,132.0,133.0,138.2,144.4,149.4,172.8.HRMS calcd for C21H23N2O:319.1805[M+H]+,found:319.1803.
5-(tert-Butyl)-5-methyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3cc)
White solid(69.6mg,67％).1H NMR(400MHz,CDCl3)δ1.16(s,9H),1.74(s,3H),2.49(dd,J1＝16.4Hz,J2＝6.4Hz,1H),3.12-3.21(m,1H),4.01(td,J1＝13.6Hz,J2＝6.8Hz,1H),4.22(dd,J1＝12.8Hz,J2＝6.8Hz,1H),6.19(s,1H),6.95(d,J＝7.6Hz,1H),6.97-7.01(m,1H),7.19-7.21(m,4H),7.28-7.35(m,3H).13C{1H}NMR(100MHz,CDCl3)δ23.1,27.8,33.9,42.7,47.5,72.1,115.8,124.0,127.1,127.2,128.1,129.5,131.8,132.7,135.9,137.1,145.6,150.1,174.9.HRMS calcd for C23H27N2O:347.2118[M+H]+,found:347.2114.
5-Cyclohexyl-5-methyl-7-phenyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3dd)
White solid(79.3mg,71％).1H NMR(400MHz,CDCl3)δ0.92-1.01(m,1H),1.07-1.32(m,4H),1.50-1.53(m,1H),1.61-1.64(m,5H),1.79-1.82(m,1H),1.89-1.92(m,1H),2.62-2.73(m,2H),2.85-2.93(m,1H),4.02-4.10(m,1H),4.14-4.21(m.1H),6.05(s,1H),7.00(d,J＝7.6Hz,1H),7.04-7.08(m,1H),7.19-7.22(m,2H),7.25-7.27(m,2H),7.31-7.34(m,3H).13C{1H}NMR(150MHz,CDCl3)δ24.5,26.3,26.6,26.8,28.0,28.7,33.5,45.4,48.7,69.6,116.5,124.6,127.4,127.7,128.1,129.2,131.9,133.3,135.8,138.0,144.8,149.2,172.5.HRMS calcd for C25H29N2O:373.2274[M+H]+,found:373.2275.
7-Butyl-5,5-diethyl-1,2-dihydro-3H,5H-benzo[c]pyrazolo[1,2-a][1,2]diazepin-3-one(3ee)
Yellow solid(77.7mg,83％).1H NMR(400MHz,CDCl3)δ0.78(t,J＝7.6Hz,6H),0.88(t,J＝7.2Hz,3H),1.26-1.33(m,2H),1.35-1.43(m,2H),1.50-1.59(m,2H),2.30-2.39(m,2H),2.52(t,J＝6.8Hz,2H),2.76(t,J＝7.2Hz,2H),4.05(t,J＝7.2Hz,2H),5.58(s,1H),7.14-7.21(m,3H),7.42(d,J＝7.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ8.8,13.9,22.3,31.4,31.7,33.3,38.5,48.0,69.5,117.0,124.9,127.1,128.0,133.6,134.2,136.7,148.6,171.8.HRMS calcdfor C20H29N2O:313.2274[M+H]+,found:313.2271.
实施例4
依照实施例2的方法和步骤a,b，通过改变反应物1和2，可以合成出各种吡唑啉酮并苯二氮杂卓类化合物3Aa-3Az和3Ba-3Bd，具体结果如下：
Figure BDA0002551614660000151
a反应条件:1(0.3mmol),2(0.3mmol),[RhCp*Cl2]2(0.0075mmol)，Zn(OAc)2(0.15mmol),NaOAc(0.15mmol),toluene(2mL),100℃,4h；b分离收率。
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代表性产物表征数据如下：
7-Phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Aa)
White solid(67.4mg,68％).1H NMR(400MHz,CDCl3)δ1.70-1.77(m,2H),1.82-1.97(m,4H),2.59-2.66(m,2H),2.78(t,J＝7.2Hz,2H),4.07(t,J＝7.2Hz,2H),6.15(s,1H),7.00-7.02(m,1H),7.04-7.08(m,1H),7.18-7.21(m,2H),7.24-7.27(m,2H),7.28-7.34(m,3H).13C{1H}NMR(100MHz,CDCl3)δ24.7,33.5,38.2,48.5,71.9,116.8,124.5,127.4,128.0,128.2,129.2,131.9,133.2,137.1,139.4,144.1,149.5,172.3.HRMS calcd forC22H23N2O:331.1805[M+H]+,found:331.1803.
9-Methyl-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ab)
White solid(64.0mg,62％).1H NMR(400MHz,CDCl3)δ1.69-1.75(m,2H),1.79-1.85(m,2H),1.89-1.94(m,2H),2.21(s,3H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),4.04(t,J＝7.2Hz,2H),6.15(s,1H),6.82(d,J＝1.6Hz,1H),7.06-7.09(m,1H),7.15(d,J＝8.4Hz,1H),7.19-7.21(m,2H),7.29-7.34(m,3H).13C{1H}NMR(100MHz,CDCl3)δ20.8,24.6,33.6,38.1,48.4,71.4,116.8,127.4,128.1,128.7,129.1,132.1,133.3,134.1,137.5,139.3,144.0,147.2,171.9.HRMS calcd for C23H25N2O:345.1961[M+H]+,found:345.1962.
9-Methyl-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ac)
White solid(64.8mg,60％).1H NMR(400MHz,CDCl3)δ1.68-1.76(m,2H),1.79-1.84(m,2H),1.87-1.96(m,2H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),3.82(s,3H),4.07(t,J＝7.2Hz,2H),6.14(s,1H),6.83-6.86(m,2H),7.03-7.08(m,2H),7.09-7.14(m,2H),7.24-7.29(m,2H).13C{1H}NMR(100MHz,CDCl3)δ24.6,33.5,38.1,48.4,55.3,71.5,113.5,116.9,124.6,128.0,130.2,131.8,133.6,136.5,136.9,138.4,149.5,159.1,172.0.HRMS calcd forC23H25N2O2:361.1911[M+H]+,found:361.1909.
9-Chloro-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ad)
Brown syrup(71.0mg,65％).1H NMR(400MHz,CDCl3)δ:1.68-1.75(m,2H),1.81-1.86(m,2H),1.89-1.97(m,2H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),4.07(t,J＝7.2Hz,2H),6.12(s,1H),6.98(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.07(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.11-7.14(m,2H),7.24-7.29(m,4H).13C{1H}NMR(100MHz,CDCl3)δ24.8,33.4,38.2,48.5,72.0,116.8,124.6,128.2,128.4,130.5,131.8,132.8,133.3,136.0,139.7,142.6,149.6,172.4.HRMScalcd for C22H22ClN2O:365.1415[M+H]+,found:365.1411.
9-Bromo-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ae)
White solid(77.1mg,63％).1H NMR(400MHz,CDCl3)δ1.70-1.76(m,2H),1.82-1.95(m,4H),2.58-2.65(m,2H),2.76(t,J＝7.2Hz,2H),4.03(t,J＝7.2Hz,2H),6.15(s,1H),7.11-7.13(m,2H),7.17-7.19(m,2H),7.31-7.38(m,4H).13C{1H}NMR(100MHz,CDCl3)δ24.8,33.3,38.3,48.7,72.2,117.6,118.3,127.7,128.4,129.1,130.7,134.4,135.2,135.7,140.8,143.5,148.7,172.4.HRMS calcd for C22H22BrN2O:409.0910[M+H]+,found:409.0906.
7-Phenyl-9-(trifluoromethyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Af)
White solid(72.9mg,61％).1H NMR(400MHz,CDCl3)δ1.71-1.80(m,2H),1.88-1.99(m,4H),2.59-2.66(m,2H),2.77(t,J＝7.2Hz,2H),4.10(t,J＝7.2Hz,2H),6.17(s,1H),7.15-7.19(m,2H),7.26-7.27(m,1H),7.31-7.37(m,4H),7.51(dd,J1＝8.4Hz,J2＝1.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ24.9,33.2,38.5,49.0,72.8,116.7,123.9(q,1JC-F＝270.1Hz),124.6(q,3JC-F＝3.6Hz),126.4(q,2JC-F＝32.5Hz),127.8,128.4,129.1,129.2(q,3JC-F＝4.4Hz),133.2,135.4,141.0,143.6,152.5,172.9.19F NMR(376MHz,CDCl3)δ-62.40(s).HRMS calcdfor C23H22F3N2O:399.1679[M+H]+,found:399.1671.
10-Methyl-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ag)
White solid(74.3mg,72％).1H NMR(400MHz,CDCl3)δ1.70-1.75(m,2H),1.80-1.96(m,4H),2.39(s,3H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),4.06(t,J＝7.2Hz,2H),6.11(s,1H),6.86-6.91(m,2H),7.04(s,1H),7.18-7.20(m,2H),7.26-7.33(m,3H).13C{1H}NMR(100MHz,CDCl3)δ20.8,24.6,33.6,38.1,48.4,71.4,116.8,127.4,128.1,128.7,129.1,132.1,133.3,134.1,137.5,139.3,144.0,147.2,171.9.HRMS calcd for C23H25N2O:345.1961[M+H]+,found:345.1958.
10-Bromo-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ah)
White solid(85.7mg,70％).1H NMR(400MHz,CDCl3)δ1.71-1.77(m,2H),1.83-1.97(m,4H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),4.04(t,J＝7.2Hz,2H),6.12(s,1H),6.87(d,J＝8.4Hz,1H),7.15-7.19(m,3H),7.29-7.34(m,3H),7.36(d,J＝2.0Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ24.8,33.2,38.3,48.8,72.4,120.0,121.2,127.5,127.6,128.3,129.2,132.0,133.3,135.9,140.0,143.8,150.8,172.5.HRMS calcd forC22H22BrN2O:409.0910[M+H]+,found:409.0904.
7-(p-Tolyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ai)
White solid(77.4mg,75％).1H NMR(400MHz,CDCl3)δ1.68-1.75(m,2H),1.80-1.94(m,4H),2.36(s,3H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),4.07(t,J＝7.2Hz,2H),6.13(s,1H),7.02-7.13(m,6H),7.23-7.27(m,2H).13C{1H}NMR(100MHz,CDCl3)δ21.2,24.7,33.5,38.2,48.5,71.8,116.8,124.5,128.0,128.9,129.0,131.9,133.4,137.0,137.1,138.9,141.2,149.5,172.2.HRMS calcd for C23H25N2O:345.1961[M+H]+,found:345.1957.
7-(4-Methoxyphenyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Aj)
White solid(65.9mg,61％).1H NMR(400MHz,CDCl3)δ1.68-1.75(m,2H),1.79-1.84(m,2H),1.87-1.96(m,2H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),3.82(s,3H),4.07(t,J＝7.2Hz,2H),6.14(s,1H),6.83-6.86(m,2H),7.03-7.14(m,4H),7.24-7.29(m,2H).13C{1H}NMR(100MHz,CDCl3)δ24.6,33.5,38.1,48.4,55.3,71.5,113.5,116.9,124.6,128.0,130.2,131.8,133.6,136.5,136.9,138.4,149.5,159.1,172.0.HRMS calcd forC23H25N2O2:361.1911[M+H]+,found:361.1911.
7-(4-Chlorophenyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Ak)
White solid(71.2mg,65％).1H NMR(400MHz,CDCl3)δ1.68-1.75(m,2H),1.81-1.86(m,2H),1.89-1.97(m,2H),2.58-2.65(m,2H),2.78(t,J＝7.2Hz,2H),4.07(t,J＝7.2Hz,2H),6.12(s,1H),6.98(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.07(td,J1＝8.0Hz,J2＝1.6Hz,1H),7.11-7.14(m,2H),7.24-7.29(m,4H).13C{1H}NMR(100MHz,CDCl3)δ24.8,33.4,38.2,48.5,72.0,116.8,124.6,128.2,128.4,130.5,131.8,132.8,133.3,136.0,139.7,142.6,149.6,172.4.HRMScalcd for C22H22ClN2O:365.1415[M+H]+,found:365.1416.
7-(4-(Trifluoromethyl)phenyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Al)
White solid(75.3mg,63％).1H NMR(400MHz,CDCl3)δ1.71-1.78(m,2H),1.84-1.99(m,4H),2.60-2.67(m,2H),2.79(t,J＝7.2Hz,2H),4.08(t,J＝7.2Hz,2H),6.13(s,1H),6.93-6.95(m,1H),7.05-7.09(m,1H),7.25-7.32(m,4H),7.57(d,J＝8.0Hz,2H).13C{1H}NMR(100MHz,CDCl3)δ24.8,33.4,38.3,48.7,72.3,116.8,124.2(q,1JC-F＝270.1Hz),124.6,125.2(q,3JC-F＝3.7Hz),128.3,129.45(q,2JC-F＝31.8Hz),129.49,131.8,132.3,135.7,140.7,147.8,149.7,172.7.19F NMR(376MHz,CDCl3)δ-62.22(s).HRMS calcd forC23H22F3N2O:399.1679[M+H]+,found:399.1674.
7-Cyclopropyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclopentan]-3-one(3Am)
White solid(63.5mg,72％).1H NMR(400MHz,CDCl3)δ0.59-0.63(m,2H),0.82-0.87(m,2H),1.58-1.74(m,5H),1.81-1.90(m,2H),2.49-2.56(m,2H),2.73(t,J＝7.2Hz,2H),4.01(t,J＝7.2Hz,2H),5.79(d,J＝0.8Hz,1H),7.16-7.18(m,1H),7.20-7.28(m,2H),7.88(dd,J1＝7.6Hz,J2＝1.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ7.1,19.0,24.7,33.5,38.3,48.6,71.7,116.5,124.6,127.5,128.8,134.0,134.9,135.3,148.4,172.4.HRMScalcd for C19H23N2O:295.1805[M+H]+,found:295.1804.
7-Phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3An)
White solid(89.8mg,87％).1H NMR(400MHz,CDCl3)δ1.31-1.40(m,1H),1.56-1.74(m,7H),2.63-2.70(m,2H),2.80(t,J＝7.2Hz,2H),4.04(t,J＝7.2Hz,2H),6.62(s,1H),7.04(d,J＝7.2Hz,1H),7.08-7.12(m,1H),7.20-7.22(m,2H),7.28-7.34(m,5H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.8,33.5,34.1,48.6,64.8,120.6,121.4,127.8,128.0,128.3,129.0,132.8,132.9,136.1,137.6,143.7,150.7,171.3.HRMS calcd for C23H25N2O:345.1961[M+H]+,found:345.1952.
9-Methyl-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Ao)
White solid(91.3mg,85％).1H NMR(400MHz,CDCl3)δ1.30-1.36(m,1H),1.55-1.73(m,7H),2.23(s,3H),2.62-2.68(m,2H),2.79(t,J＝7.6Hz,2H),4.01(t,J＝7.6Hz,2H),6.59(s,1H),6.85(d,J＝1.6Hz,1H),7.09(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.18(d,J＝8.4Hz,1H),7.21-7.24(m,2H),7.30-7.35(m,3H).13C{1H}NMR(100MHz,CDCl3)δ20.8,23.7,24.8,33.8,33.9,48.3,64.0,117.1,127.6,128.2,129.0,131.7,134.0,134.5,135.3,138.9,144.0,147.1,170.8.HRMS calcd for C24H27N2O:359.2118[M+H]+,found:359.2114.
9-Methoxy-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Ap)
Light yellow solid(86.4mg,77％).1H NMR(400MHz,CDCl3)δ1.30-1.37(m,1H),1.54-1.74(m,7H),2.65(td,J1＝12.4Hz,J2＝3.6Hz,2H),2.80(t,J＝7.6Hz,2H),3.67(s,3H),3.99(t,J＝7.6Hz,2H),6.58(d,J＝2.8Hz,1H),6.61(s,1H),6.83(dd,J1＝8.4Hz,J2＝2.8Hz,1H),7.20-7.28(m,3H),7.29-7.34(m,3H).13C{1H}NMR(100MHz,CDCl3)δ23.7,24.8,33.8,34.0,48.4,55.5,63.9,113.7,116.2,118.3,127.7,128.2,129.0,135.4,135.6,138.8,143.0,143.5,156.6,170.7.HRMS calcd for C24H27N2O2:375.2067[M+H]+,found:375.2055.
9-Fluoro-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Aq)
White solid(79.3mg,73％).1H NMR(400MHz,CDCl3)δ1.30-1.39(m,1H),1.54-1.75(m,7H),2.63-2.69(m,2H),2.80(t,J＝7.2Hz,2H),4.01(t,J＝7.2Hz,2H),6.65(s,1H),6.75(dd,J1＝9.6Hz,J2＝2.8Hz,1H),6.96-7.01(m,1H),7.20-7.26(m,3H),7.31-7.36(m,3H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.8,33.8,34.0,48.7,64.4,114.9(d,2JC-F＝22.4Hz),117.7(d,2JC-F＝22.4Hz),118.6(d,3JC-F＝8.7Hz),127.8,128.4,129.0,136.0(d,3JC-F＝8.0Hz),136.5,137.8(d,4JC-F＝2.1Hz),143.3,145.7(d,4JC-F＝2.2Hz),159.7(d,1JC-F＝242.7Hz),171.1.19FNMR(376MHz,CDCl3)δ-117.32–-117.26(m).HRMS calcd forC23H24FN2O:363.1867[M+H]+,found:363.1861.
9-Bromo-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Ar)
Light yellow solid(95.0mg,75％).1H NMR(400MHz,CDCl3)δ1.32-1.39(m,1H),1.54-1.76(m,7H),2.62-2.69(m,2H),2.78(t,J＝7.2Hz,2H),4.00(t,J＝7.2Hz,2H),6.64(s,1H),7.15-7.17(m,2H),7.18-7.21(m,2H),7.32-7.36(m,3H),7.39(dd,J1＝8.4Hz,J2＝2.4Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.8,33.6,34.0,48.6,64.6,118.0,118.9,127.9,128.4,129.0,131.0,134.0,136.0,136.8,137.4,143.4,148.6,171.2.HRMS calcdfor C23H24BrN2O:423.1067[M+H]+,found:423.1066.
7-Phenyl-9-(trifluoromethyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3As)
White solid(103.9mg,84％).1H NMR(400MHz,CDCl3)δ1.32-1.42(m,1H),1.56-1.75(m,7H),2.64-2.72(m,2H),2.79(t,J＝7.6Hz,2H),4.07(t,J＝7.6Hz,2H),6.70(s,1H),7.16-7.20(m,2H),7.30-7.38(m,5H),7.54(dd,J1＝8.4Hz,J2＝1.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ23.5,24.8,33.5,34.2,48.8,65.1,117.4,123.9(q,1JC-F＝270.1Hz),125.0(q,3JC-F＝3.6Hz),126.9(q,1JC-F＝32.5Hz),128.0,128.5,128.7(q,3JC-F＝3.6Hz),129.0,134.1,137.2,143.6,152.4,171.6.19F NMR(376MHz,CDCl3)δ-62.22(s).HRMS calcdfor C24H24F3N2O:413.1835[M+H]+,found:413.1829.
10-Methoxy-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3At)
White solid(79.7mg,71％).1H NMR(400MHz,CDCl3)δ1.34-1.40(m,1H),1.59-1.73(m,7H),2.65(td,J1＝13.2Hz,J2＝4.0Hz,2H),2.79(t,J＝7.6Hz,2H),3.84(s,3H),4.01(t,J＝7.2Hz,2H),6.49(s,1H),6.65(dd,J1＝8.8Hz,J2＝2.4Hz,1H),6.81(d,J＝2.4Hz,1H),6.96(d,J＝8.4Hz,1H),7.20-7.23(m,2H),7.29-7.34(m,3H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.8,33.6,33.9,48.5,55.5,64.4,104.5,109.1,126.7,127.5,128.2,129.0,132.6,133.7,138.4,144.2,150.7,159.4,171.1.HRMS calcd forC24H27N2O2:375.2067[M+H]+,found:375.2060.
10-Bromo-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Au)
White solid(103.8mg,82％).1H NMR(400MHz,CDCl3)δ1.33-1.39(m,1H),1.54-1.75(m,7H),2.66(td,J1＝13.6Hz,J2＝4.8Hz,2H),2.79(t,J＝7.2Hz,2H),4.01(t,J＝7.2Hz,2H),6.62(s,1H),6.91(d,J＝8.4Hz,1H),7.17-7.19(m,2H),7.22(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.31-7.34(m,3H),7.40(d,J＝1.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.8,33.5,34.1,48.6,64.8,120.6,121.4,127.8,128.0,128.3,129.0,132.8,132.9,136.1,137.6,143.7,150.7,171.3.HRMS calcd for C23H24BrN2O:423.1067[M+H]+,found:423.1062.
2-Methyl-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Av)
White solid(79.5mg,74％).1H NMR(400MHz,CDCl3)δ1.24(d,J＝6.8Hz,3H),1.32-1.82(m,7H),1.97(d,J＝12.8Hz,1H),2.51(td,J1＝13.2Hz,J2＝4.8Hz,1H),2.82(td,J1＝13.2Hz,J2＝4.4Hz,1H),3.14-3.23(m,1H),3.50(t,J＝12.8Hz,1H),4.27-4.32(m,1H),6.61(s,1H),7.02-7.10(m,2H),7.20-7.22(m,2H),7.25-7.33(m,5H).13C{1H}NMR(100MHz,CDCl3)δ13.8,23.4,23.8,24.9,33.2,34.7,37.4,56.3,64.5,117.4,124.7,127.5,128.1,128.2,129.1,131,6,133.9,135.5,138.5,144.2,149.5,173.8.HRMS calcd for C24H27N2O:359.2118[M+H]+,found:359.2118.
2,2-Dimethyl-7-phenyl-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Aw)
White solid(89.3mg,80％).1H NMR(400MHz,CDCl3)δ1.27(s,6H),1.41-1.47(m,1H),1.54-1.72(m,7H),2.65-2.71(m,2H),3.92(s,2H),6.43(s,1H),6.89-6.97(m,2H),7.17-7.19(m,2H),7.21-7.22(m,2H),7.28-7.33(m,3H).13C{1H}NMR(100MHz,CDCl3)δ23.1,24.5,25.2,33.8,42.8,62.2,63.3,118.5,122.7,127.2,127.9,128.2,129.0,131.0,132.4,136.6,139.6,144.5,150.5,176.1.HRMS calcd for C25H29N2O:373.2274[M+H]+,found:373.2269.
7-(4-Ethylphenyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Ax)
White solid(99.4mg,89％).1H NMR(400MHz,CDCl3)δ1.25(t,J＝7.6Hz,3H),1.32-1.37(m,1H),1.58-1.72(m,7H),2.62-2.69(m,4H),2.80(t,J＝7.2Hz,2H),4.04(t,J＝7.6Hz,2H),6.60(s,1H),7.06-7.16(m,6H),7.27-7.29(m,2H).13C{1H}NMR(100MHz,CDCl3)δ15.6,23.6,24.8,28.6,33.8,33.9,48.4,64.3,117.2,124.8,127.7,128.2,129.0,131.6,134.2,134.9,138.5,141.4,143.7,149.4,171.1.HRMS calcd for C25H29N2O:373.2274[M+H]+,found:373.2271.
7-(4-Methoxyphenyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Ay)
Yellow syrup(86.6mg,77％).1H NMR(400MHz,CDCl3)δ1.32-1.38(m,1H),1.54-1.73(m,7H),2.62-2.68(m,2H),2.80(t,J＝7.6Hz,2H),3.81(s,3H),4.03(t,J＝7.6Hz,2H),6.57(s,1H),6.83-6.87(m,2H),7.06-7.11(m,2H),7.12-7.16(m,2H),7.26-7.28(m,2H).13C{1H}NMR(100MHz,CDCl3)δ23.7,24.8,33.8,33.9,48.3,55.3,64.2,113.6,117.2,124.9,128.3,130.1,131.5,134.2,134.3,136.5,138.3,149.4,159.3,171.0.HRMS calcdfor C24H27N2O2:375.2067[M+H]+,found:375.2059.
7-(4-(Trifluoromethyl)phenyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Az)
Yellow solid(101.4mg,82％).1H NMR(400MHz,CDCl3)δ1.31-1.41(m,1H),1.53-1.64(m,2H),1.69-1.76(m,5H),2.68(td,J1＝13.2Hz,J2＝4.4Hz,2H),2.81(t,J＝7.2Hz,2H),4.05(t,J＝7.2Hz,2H),6.64(s,1H),6.97-6.99(m,1H),7.09-7.13(m,1H),7.29-7.33(m,4H),7.58(d,J＝8.0Hz,2H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.8,33.7,33.9,48.5,64.6,117.3,124.2(q,1JC-F＝270.2Hz),125.0,125.2(q,3JC-F＝3.6Hz),128.6,129.3,129.6(q,2JC-F＝32.5Hz),131.3,133.2,136.9,137.4,147.7,149.5,171.4.19F NMR(376MHz,CDCl3)δ-62.42(s).HRMS calcd for C24H24F3N2O:413.1835[M+H]+,found:413.1833.
7-(m-Tolyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Ba)
Light yellow solid(92.4mg,86％).1H NMR(400MHz,CDCl3)δ1.33-1.38(m,1H),1.55-1.74(m,7H),2.33(s,3H),2.62-2.70(m,2H),2.80(t,J＝7.2Hz,2H),4.04(t,J＝7.6Hz,2H),6.59(s,1H),6.99-7.05(m,3H),7.08-7.12(m,2H),7.21(t,J＝7.2Hz,1H),7.26-7.29(m,2H).13C{1H}NMR(100MHz,CDCl3)δ21.5,23.6,24.8,33.8,33.9,48.4,64.3,117.2,124.9,126.2,128.1,128.2,128.3,129.7,131.6,134.1,135.2,137.8,138.7,144.1,149.4,171.2.HRMS calcd forC24H27N2O:359.2118[M+H]+,found:359.2114.
7-(3-Chlorophenyl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Bb)
White solid(99.8mg,88％).1H NMR(400MHz,CDCl3)δ1.33-1.40(m,1H),1.53-1.63(m,2H),1.68-1.75(m,5H),2.63-2.69(m,2H),2.80(t,J＝7.6Hz,2H),4.04(t,J＝7.6Hz,2H),6.60(s,1H),7.02(d,J＝7.2Hz,1H),7.08-7.14(m,2H),7.18(d,J＝1.6Hz,1H),7.23-7.32(m,4H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.8,33.7,33.9,48.5,64.4,117.3,125.0,127.3,127.7,128.6,129.0,129.5,131.4,133.3,134.1,136.3,137.4,145.9,149.5,171.3.HRMS calcd forC23H24ClN2O:379.1572[M+H]+,found:379.1572.
7-(Thiophen-2-yl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Bc)
White solid(85.4mg,81％).1H NMR(400MHz,CDCl3)δ1.26-1.38(m,1H),1.50-1.72(m,7H),2.63(td,J1＝12.4Hz,J2＝4.0Hz,2H),2.80(t,J＝7.6Hz,2H),4.02(t,J＝7.6Hz,2H),6.80(s,1H),6.86(dd,J1＝3.2Hz,J2＝0.8Hz,1H),6.97(dd,J1＝5.2Hz,J2＝3.6Hz,1H),7.16-7.20(m,1H),7.23(dd,J1＝5.2Hz,J2＝1.2Hz,1H),7.27-7.29(m,1H),7.31-7.35(m,1H),7.41(dd,J1＝8.0Hz,J2＝1.6Hz,1H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.7,33.7,33.8,48.2,64.0,117.4,125.0,125.1,126.6,127.2,128.8,131.2,132.1,133.4,134.8,146.5,149.1,170.7.HRMS calcd for C21H23N2OS:351.1526[M+H]+,found:351.1523.
7-(Pyridin-3-yl)-1,2-dihydro-3H-spiro[benzo[c]pyrazolo[1,2-a][1,2]diazepine-5,1'-cyclohexan]-3-one(3Bd)
White solid(86.9mg,84％).1H NMR(400MHz,CDCl3)δ1.34-1.41(m,1H),1.54-1.65(m,2H),1.73-1.76(m,5H),2.68(td,J1＝12.8Hz,J2＝4.0Hz,2H),2.81(t,J＝7.6Hz,2H),4.06(t,J＝7.6Hz,2H),6.65(s,1H),7.00-7.01(m,1H),7.10-7.14(m,1H),7.23-7.28(m,1H),7.31-7.33(m,2H),7.47(dt,J1＝8.0Hz,J2＝2.0Hz,1H),8.55-8.57(m,2H).13C{1H}NMR(100MHz,CDCl3)δ23.6,24.7,33.7,34.0,48.6,64.7,117.3,123.1,125.1,128.7,131.1,133.0,135.3,136.3,136.9,139.7,148.8,149.5,149.8,171.5.HRMS calcd forC22H24N3O:346.1914[M+H]+,found:346.1908.
以1a和2a在实施例2标准条件下得到3a为例，经过对比试验验证(实验细节省略)，推测反应原理如下：
Figure BDA0002551614660000231
Figure BDA0002551614660000241
需要特别指出的是，迁移插入的区域选择性来源于OH和Rh(III)额外络合配位，生成中间体III，接着中间体III经历去金属化/质子化生成中间体IV,接着最可能在体系原位生成的醋酸帮助下，Rh(III)发生氧化插入到C-O键中间，生成中间体V，脱除水分子后形成中间体VI，VI发生还原消除，生成产物3a，同时释放出Rh(III)催化剂，用于下一轮催化。
实施例5
本发明所合成的产物吡唑啉酮并苯二氮杂卓类化合物3可以进行一系列反应，从而合成进一步的衍生物。例如：
Figure BDA0002551614660000242
向3a(60.8mg，0.2mmol)的MeOH/DCM(2mL，10/3)溶液中添加Pd/C(10wt％，10mg)。在室温条件下将混合物在H2(气球，1atm)下搅拌24小时。反应结束后，将反应混合物过硅藻土抽滤并在减压下浓缩。残余物过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得到白色固体产物4a(58.2mg，95％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ1.53(s,3H),1.65(s,3H),1.78(dd,J1＝14.4Hz,J2＝4.4Hz,1H),2.42-2.49(m,1H),2.83-2.95(m,2H),3.78-3.86(m,1H),4.12(ddd,J1＝12.8Hz,J2＝7.2Hz,J3＝2.8Hz,1H),4.42(dd,J1＝12.4Hz,J2＝4.0Hz,1H),6.83(d,J＝7.6Hz,1H),6.89-6.92(m,1H),7.07-7.11(m,2H),7.14-7.21(m,3H),7.27-7.30(m,2H).13C{1H}NMR(100MHz,CDCl3)δ24.3,27.2,33.5,46.9,48.6,48.7,60.0,116.4,124.4,126.3,126.7,128.3,128.7,132.6,136.2,147.7,149.3,173.4.HRMScalcd for C20H23N2O:307.1805[M+H]+,found:307.1805.
Figure BDA0002551614660000251
在0℃下，向3a(60.8mg，0.2mmol)的THF(5mL)溶液中缓慢加入LiAlH4(0.4mL，1M)，然后在室温搅拌反应2h。反应结束后，加入水淬灭反应，浓缩并用EtOAc萃取。合并有机相，用无水硫酸钠干燥，过滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝3/1)得到黄色浆状物5a(33.9mg，55％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3)δ1.35(s,6H),1.95-2.01(m,2H),3.61-3.64(m,4H),3.80(t,J＝5.6Hz,2H),6.08(s,1H),6.87(td,J1＝7.2Hz,J2＝0.8Hz,1H),6.92(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.04(d,J＝7.6Hz,1H),7.13-7.18(m,3H),7.25-7.33(m,3H).13C{1H}NMR(100MHz,CDCl3)δ27.8,30.2,54.4,61.5,62.8,115.4,122.3,126.8,127.2,128.0,129.5,130.5,133.3,136.2,143.6,146.0,151.8.HRMS calcd forC20H25N2O:309.1961[M+H]+,found:309.1962.
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 (5)

1.一种吡唑啉酮并苯二氮杂卓类化合物的合成方法，其特征在于，包括如下操作：以1-芳基吡唑烷酮类化合物1和炔丙醇类化合物2为原料，在铑催化剂和添加剂存在下，有机溶剂中反应得到吡唑啉酮并苯二氮杂卓类化合物3，反应方程式为：
Figure FDA0003015013530000011
其中：R1为氢、卤素、三氟甲基、氰基、硝基、C1-4烷基或C1-4烷氧基；R2为氢或C1-4烷基；R3为氢或C1-4烷基；R4为C1-6链状烷基、C3-6环烷基、噻吩基、吡啶基、苯基或取代苯基，取代苯基苯环上的取代基为卤素、三氟甲基、硝基、C1-4烷基或C1-4烷氧基；R5和R6各自独立为C1-4烷基、C3-6环烷基或共同组成C4-6环烷基；反应溶剂选自1,2-二氯乙烷、甲苯、二氯甲烷或丙酮；所述铑催化剂为[RhCp*Cl2]2或RhCp*(OAc)2；所述添加剂为醋酸锌与醋酸、醋酸钠、醋酸铯、醋酸钾其中之一组成。
2.根据权利要求1所述吡唑啉酮并苯二氮杂卓类化合物的合成方法，其特征在于：反应溶剂选自甲苯。
3.根据权利要求1所述吡唑啉酮并苯二氮杂卓类化合物的合成方法，其特征在于：所述1-芳基吡唑烷酮类化合物1、炔丙醇类化合物2、添加剂和催化剂的投料摩尔比为1:1-1.5:0.5-1.0:0.02-0.03。
4.根据权利要求1-3任意一项所述吡唑啉酮并苯二氮杂卓类化合物的合成方法，其特征在于：所述反应温度为80-110℃。
5.吡唑啉酮并苯二氮杂卓类化合物3的应用，其特征在于：包括权利要求1-4任意一项所述方法制备得到化合物3，然后化合物3采用钯碳催化氢化得到化合物4；采用四氢铝锂还原，得到化合物5，反应方程式为：
Figure FDA0003015013530000021
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