CN113185523A - 一种3-吲哚酮[螺]-3h-吲哚类化合物的合成方法 - Google Patents

一种3-吲哚酮[螺]-3h-吲哚类化合物的合成方法 Download PDF

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CN113185523A
CN113185523A CN202110531496.5A CN202110531496A CN113185523A CN 113185523 A CN113185523 A CN 113185523A CN 202110531496 A CN202110531496 A CN 202110531496A CN 113185523 A CN113185523 A CN 113185523A
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indolone
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范学森
蔡炘原
周倩婷
张新迎
宋霞
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Abstract

本发明公开了一种3‑吲哚酮[螺]‑3H‑吲哚类化合物的合成方法，属于有机合成技术领域。将N‑芳基脒类化合物1、重氮吲哚酮类化合物2、铑或钌催化剂、酸性添加剂和有机溶剂混合，升温反应得到3‑吲哚酮[螺]‑3H‑吲哚类化合物3。本发明通过N‑芳基脒类化合物和重氮吲哚酮类化合物之间发生串联反应，高效地、区域选择性地合成了3‑吲哚酮[螺]‑3H‑吲哚类化合物，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。

Description

一种3-吲哚酮[螺]-3H-吲哚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3-吲哚酮[螺]-3H-吲哚类化合物的合成方法。
背景技术
螺环具有较高的刚性和独特的三维结构，在药物开发的先导化合物中引入螺环往往可以有效改变母体化合物的理化性能并提高其药物活性。其中，在吲哚酮的3-位引入螺环骨架所形成的许多化合物都表现出显著的抗病毒、抗菌、抗癌、抗结核和抗疟活性，是药物发现的重要来源。
鉴于其重要性，人们研究并开发了多种在吲哚酮的3-位引入螺环骨架的有效策略，这主要包括：甲亚胺叶立德与活泼烯烃的环加成反应、N-芳基酰胺的分子内氧化C(sp2)-C(sp3)键形成、Rh(III)催化下吲哚酮重氮化合物与烯基叠氮的烯基化/环化串联反应、Rh(II)催化下吲哚酮重氮化合物与异氰酸酯之间的[4+1]环加成反应等。尽管已有这些有效方法，但3-吲哚酮[螺]-3H-吲哚衍生物高效、经济的合成方法到目前为止尚未见报道。
发明内容
本发明解决的技术问题是提供了一种3-吲哚酮[螺]-3H-吲哚类化合物的合成方法，该方法通过N-芳基脒类化合物和重氮吲哚酮类化合物之间发生串联反应，高效地、区域选择性地合成了3-吲哚酮[螺]-3H-吲哚类化合物，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。
本发明为解决上述技术问题采用如下技术方案，一种3-吲哚酮[螺]-3H-吲哚类化合物的合成方法，包括如下操作：将N-芳基脒类化合物1、重氮吲哚酮类化合物2、铑或钌催化剂、酸性添加剂和有机溶剂混合，升温反应得到3-吲哚酮[螺]-3H-吲哚类化合物3，反应方程式为：
Figure BDA0003068056630000011
其中R1为氢、卤素、三氟甲基、C1-4烷基、C1-4烷氧基或苄氧基，R2为C1-4烷基、苯基或取代苯基，取代苯基苯环上的取代基为卤素、C1-4烷基或C1-4烷氧基，R3为氢、卤素、C1-4烷基或C1-4烷氧基，R4为C1-4烷基、苄基、C1-4烷基酰基、磺酰基、叔丁氧羰基或芳基甲酰基。
进一步地，在上述技术方案中，所述反应溶剂为起到溶解原料的作用，优选1,2-二氯乙烷、甲醇、丙酮、四氢呋喃、乙腈或甲苯。
进一步地，在上述技术方案中，所述酸性添加剂为醋酸、三甲基乙酸、苯甲酸、2,4,6-三甲基苯甲酸或1-金刚烷甲酸。
进一步地，在上述技术方案中，所述催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体([RhCp*Cl2]2)、二氯双(4-甲基异丙基苯基)钌(II)([Ru(p-cymene)Cl2]2)、二氯(五甲基环戊二烯基)合铱(III)二聚体([IrCp*Cl2]2)、五羰基溴化锰(MnBr(CO)5)、水合三氯化铑或五甲基环戊二烯基羰基二碘化钴(CoCp*(CO)I2)。优选催化剂为二氯(五甲基环戊二烯基)合铑(III)二聚体([RhCp*Cl2]2)或二氯双(4-甲基异丙基苯基)钌(II)([Ru(p-cymene)Cl2]2)。
进一步地，在上述技术方案中，所述反应温度为0-100℃。
进一步地，在上述技术方案中，所述N-芳基脒类化合物1、重氮吲哚酮类化合物2、酸性添加剂与催化剂摩尔比为1:1-2:0.5-2:0.02-0.06。
进一步地，在上述技术方案中，反应在空气氛围下进行。
本发明还进一步提供了上述3-吲哚酮[螺]-3H-吲哚类化合物衍生化反应，生成化合物4-6，具体反应条件如下：
1)：3-吲哚酮[螺]-3H-吲哚类化合物3在苯甲酸存在下与硼氢化钠反应，得到吲哚类化合物4，对应结构通式为
Figure BDA0003068056630000021
2)：3-吲哚酮[螺]-3H-吲哚类化合物3在四氢铝锂存在下反应，得到吲哚类化合物5，对应结构通式为
Figure BDA0003068056630000022
3)：3-吲哚酮[螺]-3H-吲哚类化合物3，对应R4＝Boc时，在碳酸钠存在下反应，得到吲哚类化合物6，对应结构通式为
Figure BDA0003068056630000023
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N-芳基脒和重氮吲哚酮类化合物的一锅串联反应，即可高选择性地合成3-吲哚酮[螺]-3H-吲哚类化合物；(2)原料价廉易得；(3)反应条件温和，操作简便；(4)反应的原子经济性高，符合绿色化学的要求。
说明书附图
图1为实施例1-3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 BDA0003068056630000031
向15mL反应瓶中依次加入1a、2a、溶剂、添加剂和催化剂，在空气氛围下，盖上塞子密封，将其置于油浴中升温搅拌反应。反应结束，冷却至室温，饱和NaHCO3溶液淬灭反应，萃取干燥，过滤旋干，硅胶柱分离(石油醚/乙酸乙酯＝10/1)得白色固体产物3a。
通过改变反应的溶剂、添加剂、催化剂、反应温度和反应物之间的当量比等反应条件，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 BDA0003068056630000032
Figure BDA0003068056630000041
实施例2
Figure BDA0003068056630000042
向15mL反应瓶中依次加入1a(35.2mg,0.2mmol)、2a(52.0mg,0.3mmol)、1,2-二氯乙烷(2mL)、二氯(五甲基环戊二烯基)合铑(III)二聚体([RhCp*Cl2]2,2.5mg,0.004mmol)、醋酸铯(1.9mg,0.01mmol)和1-金刚烷甲酸(72.1mg,0.4mmol)，空气氛围下，盖上塞子密封，置于60℃油浴搅拌反应4小时。反应结束，冷却至室温，饱和NaHCO3溶液淬灭反应，萃取干燥，过滤旋干，硅胶柱分离(石油醚/乙酸乙酯＝10/1)得白色固体产物3a(44mg,72％)。1HNMR(CDCl3,400MHz):δ7.66(d,J＝8.0Hz,1H),7.39-7.32(m,2H),7.08(t,J＝7.6Hz,1H),7.01-6.97(m,2H),6.80(d,J＝7.6Hz,1H),6.77-6.75(m,1H),3.35(s,3H),1.17(s,9H).13C{1H}NMR(CDCl3,100MHz):δ187.0,172.3,156.2,144.7,139.8,129.2,128.9,127.0,126.2,124.1,123.2,121.3,120.6,108.9,70.1,38.5,29.4,27.1.HRMS(ESI)m/z:[M+Na]+Calcdfor C20H20N2NaO 327.1468；Found 327.1456.
实施例3
依照实施例2的方法和步骤，通过改变反应物1和2，合成出各种3-吲哚酮[螺]-3H-吲哚类化合物3，具体结果见表2。
表2各种3-吲哚酮[螺]-3H-吲哚类化合物3的合成a,b
Figure BDA0003068056630000051
a反应条件：1(0.2mmol)，2(0.3mmol)，[RhCp*Cl2]2(0.004mmol)，CsOAc(0.01mmol)，1-AdCO2H(0.4mmol)，DCE(2mL)，60℃，4h；b分离收率。
代表性产物表征数据如下：
2-(tert-Butyl)-1',5-dimethylspiro[indole-3,3'-indolin]-2'-one(3b)
White solid(45mg,71％).1H NMR(CDCl3,400MHz):δ7.53(d,J＝8.0Hz,1H),7.37(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.13(d,J＝7.6Hz,1H),7.02-6.98(m,2H),6.78-6.76(m,1H),6.60(s,1H),3.35(s,3H),2.24(s,3H),1.16(s,9H).13C{1H}NMR(CDCl3,100MHz):δ185.9,172.6,153.9,144.7,139.9,136.1,129.5,129.1,127.3,124.2,123.1,121.9,120.2,108.9,69.9,38.4,29.4,27.1,21.3.HRMS(ESI)m/z:[M+H]+Calcd for C21H23N2O319.1805；Found 319.1798.
2-(tert-Butyl)-5-isopropyl-1'-methylspiro[indole-3,3'-indolin]-2'-one(3c)
White solid(51mg,74％).1H NMR(CDCl3,400MHz):δ7.57(d,J＝8.0Hz,1H),7.37(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.21(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.01-6.98(m,2H),6.78-6.76(m,1H),6.62(d,J＝1.2Hz,1H),3.36(s,3H),2.82-2.75(m,1H),1.15-1.12(m,15H).13C{1H}NMR(CDCl3,100MHz):δ186.1,172.6,154.3,147.3,144.7,139.8,129.1,127.3,126.8,124.2,123.1,120.3,119.6,108.9,70.0,38.4,34.1,29.4,27.1,24.2,24.1.HRMS(ESI)m/z:[M+H]+Calcd for C23H27N2O 347.2118；Found 347.2105.
2-(tert-Butyl)-5-methoxy-1'-methylspiro[indole-3,3'-indolin]-2'-one(3d)
White solid(38mg,57％).1H NMR(CDCl3,600MHz):δ7.56(d,J＝8.4Hz,1H),7.37(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.00(t,J＝7.8Hz,2H),6.86(dd,J1＝8.4Hz,J2＝2.4Hz,1H),6.78(d,J＝7.2Hz,1H),6.34(d,J＝2.4Hz,1H),3.69(s,3H),3.34(s,3H),1.15(s,9H).13C{1H}NMR(CDCl3,150MHz):δ184.8,172.4,158.5,149.7,144.6,141.3,129.2,127.2,124.2,123.2,121.0,113.7,108.9,107.9,70.2,55.7,38.3,29.4,27.1.HRMS(ESI)m/z:[M+H]+Calcd for C21H23N2O2 335.1754；Found 335.1741.
2-(tert-Butyl)-5-fluoro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3e)
White solid(45mg,70％).1H NMR(CDCl3,400MHz):δ7.59(dd,J1＝8.4Hz,J2＝4.4Hz,1H),7.41-7.37(m,1H),7.05-6.99(m,3H),6.77(d,J＝7.2Hz,1H),6.52(dd,J1＝8.0Hz,J2＝2.8Hz,1H),3.35(s,3H),1.15(s,9H).13C{1H}NMR(CDCl3,150MHz):δ186.9(d,5JC-F＝3.3Hz),171.7,161.4(d,1JC-F＝243.9Hz),152.3(d,4JC-F＝2.3Hz),144.6,141.4(d,3JC-F＝8.7Hz),129.5,126.4,124.2,123.4,121.4(d,3JC-F＝8.7Hz),115.6(d,2JC-F＝23.0Hz),109.3(d,2JC-F＝25.2Hz),109.1,70.3(d,4JC-F＝2.1Hz),38.5,29.3,27.1.19F NMR(CDCl3,376MHz):δ-115.7(td,J1＝8.3Hz,J2＝4.1Hz).HRMS(ESI)m/z:[M+Na]+Calcd forC20H19FN2NaO 345.1374；Found 345.1359.
2-(tert-Butyl)-5-chloro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3f)
White solid(52mg,77％).1H NMR(CDCl3,400MHz):δ7.57(d,J＝8.0Hz,1H),7.39(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.31(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.04-6.99(m,2H),6.77-6.76(m,2H),3.35(s,3H),1.15(s,9H).13C{1H}NMR(CDCl3,100MHz):δ187.6,171.5,154.8,144.6,141.3,131.7,129.5,129.1,126.2,124.2,123.4,121.9,121.5,109.1,70.2,38.5,29.3,27.2.HRMS(ESI)m/z:[M+Na]+Calcd for C20H19ClN2NaO 361.1078；Found361.1067.
5-Bromo-2-(tert-butyl)-1'-methylspiro[indole-3,3'-indolin]-2'-one(3g)
White solid(58mg,76％).1H NMR(CDCl3,400MHz):δ7.52(d,J＝8.4Hz,1H),7.46(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.39(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.04-6.99(m,2H),6.91(d,J＝1.6Hz,1H),6.76(d,J＝7.2Hz,1H),3.35(s,3H),1.15(s,9H).13C{1H}NMR(CDCl3,100MHz):δ187.7,171.5,155.2,144.6,141.7,132.0,129.6,126.1,124.7,124.2,123.4,122.0,119.5,109.2,70.2,38.5,29.3,27.2.HRMS(ESI)m/z:[M+H]+Calcd forC20H20BrN2O 383.0754；Found 383.0739.
2-(tert-Butyl)-5-iodo-1'-methylspiro[indole-3,3'-indolin]-2'-one(3h)
White solid(58mg,67％).1H NMR(CDCl3,400MHz):δ7.67(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.42-7.37(m,2H),7.09(s,1H),7.04-6.99(m,2H),6.76(d,J＝7.2Hz,1H),3.35(s,3H),1.15(s,9H).13C{1H}NMR(CDCl3,150MHz):δ187.6,171.5,155.9,144.6,141.9,138.0,130.4,129.5,126.1,124.2,123.4,122.5,109.1,90.5,70.0,38.5,29.3,27.2.HRMS(ESI)m/z:[M+H]+Calcd for C20H20IN2O 431.0615；Found 431.0614.
2-(tert-Butyl)-1'-methyl-5-phenylspiro[indole-3,3'-indolin]-2'-one(3i)
White solid(26mg,34％).1H NMR(CDCl3,400MHz):δ7.72(d,J＝8.4Hz,1H),7.57(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.44(d,J＝7.2Hz,2H),7.40-7.33(m,3H),7.28(d,J＝7.6Hz,1H),7.02-6.97(m,3H),6.81(d,J＝7.2Hz,1H),3.37(s,3H),1.19(s,9H).13C{1H}NMR(CDCl3,100MHz):δ187.3,172.2,155.6,144.7,140.9,140.5,139.6,129.3,128.7,128.1,127.2,127.0,124.2,123.3,120.8,120.3,109.0,70.2,38.6,29.4,27.1.HRMS(ESI)m/z:[M+H]+Calcd for C26H25N2O 381.1961；Found 381.1958.
2-(tert-Butyl)-1',6-dimethylspiro[indole-3,3'-indolin]-2'-one(3j)
White solid(48mg,75％).1H NMR(CDCl3,600MHz):δ7.48(s,1H),7.35(td,J1＝7.8Hz,J2＝1.2Hz,1H),6.99-6.97(m,2H),6.90(dd,J1＝7.8Hz,J2＝0.6Hz,1H),6.76(dd,J1＝7.8Hz,J2＝0.6Hz,1H),6.68(d,J＝7.8Hz,1H),3.33(s,3H),2.38(s,3H),1.16(s,9H).13C{1H}NMR(CDCl3,150MHz):δ187.2,172.5,156.4,144.7,139.0,136.9,129.1,127.2,126.8,124.1,123.1,121.4,120.9,108.9,69.8,38.5,29.4,27.0,21.6.HRMS(ESI)m/z:[M+H]+Calcd for C21H23N2O 319.1805；Found 319.1801.
2-(tert-Butyl)-4-fluoro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3k)
White solid(47mg,73％).1H NMR(CDCl3,600MHz):δ7.46(d,J＝7.8Hz,1H),7.38(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.34-7.31(m,1H),7.01-6.98(m,2H),6.79-6.76(m,2H),3.37(s,3H),1.16(s,9H).13C{1H}NMR(CDCl3,100MHz):δ187.9,170.9,158.7(d,3JC-F＝4.3Hz),156.9(d,1JC-F＝250.7Hz),144.8,130.7(d,3JC-F＝7.9Hz),129.5,125.3(d,2JC-F＝14.4Hz),124.6,123.7,123.1,116.6(d,4JC-F＝3.6Hz),113.5(d,2JC-F＝19.5Hz),109.0,68.7(d,3JC-F＝3.6Hz),38.7,29.4,27.1.19F NMR(CDCl3,376MHz):δ-120.1(dd,J1＝8.3Hz,J2＝5.6Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C20H19FN2NaO 345.1374；Found 345.1368.
2-(tert-Butyl)-6-chloro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3l)
White solid(53mg,78％).1H NMR(CDCl3,400MHz):δ7.64(d,J＝1.6Hz,1H),7.38(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.06(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.02-6.98(m,2H),6.75-6.71(m,2H),3.33(s,3H),1.15(s.9H).13C{1H}NMR(CDCl3,100MHz):δ189.1,171.6,157.4,144.7,138.2,134.6,129.5,126.3,126.1,124.1,123.4,122.1,121.2,109.1,69.8,38.7,29.3,27.1.HRMS(ESI)m/z:[M+Na]+Calcd for C20H19ClN2NaO 361.1078；Found361.1070.
6-Bromo-2-(tert-butyl)-1'-methylspiro[indole-3,3'-indolin]-2'-one(3m)
White solid(53mg,69％).1H NMR(CDCl3,600MHz):δ7.81(d,J＝1.2Hz,1H),7.38(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.22(dd,J1＝7.8Hz,J2＝1.8Hz,1H),7.02-6.99(m,2H),6.75(d,J＝6.6Hz,1H),6.67(d,J＝7.8Hz,1H),3.34(s,3H),1.15(s,9H).13C{1H}NMR(CDCl3,100MHz):δ189.0,171.5,157.6,144.7,138.7,129.5,129.0,126.2,124.15,124.12,123.4,122.5,122.4,109.1,69.9,38.6,29.3,27.1.HRMS(ESI)m/z:[M+Na]+Calcdfor C20H19BrN2NaO 405.0573；Found 405.0563.
2-(tert-Butyl)-1',7-dimethylspiro[indole-3,3'-indolin]-2'-one(3n)
White solid(35mg,55％).1H NMR(CDCl3,600MHz):δ7.35(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.13(d,J＝7.8Hz,1H),6.99-6.95(m,3H),6.76(dd,J1＝7.8Hz,J2＝1.2Hz,1H),6.60(d,J＝7.2Hz,1H),3.34(s,3H),2.63(s,3H),1.16(s,9H).13C{1H}NMR(CDCl3,100MHz):δ185.0,172.7,155.0,144.7,139.7,130.6,130.3,129.0,127.4,125.9,124.1,123.1,118.6,108.8,70.3,38.5,29.5,27.0,17.1.HRMS(ESI)m/z:[M+H]+Calcd for C21H23N2O319.1805；Found 319.1801.
2-(tert-Butyl)-7-fluoro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3o)
White solid(27mg,42％).1H NMR(CDCl3,400MHz):δ7.39(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.08-6.99(m,4H),6.78-6.76(m,1H),6.60-6.58(m,1H),3.35(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,150MHz):δ187.6,171.6,153.6(d,1JC-F＝253.8Hz),144.7,143.1(d,2JC-F＝11.0Hz),142.9(d,3JC-F＝3.3Hz),129.5,127.6(d,3JC-F＝6.5Hz),126.4,124.1,123.4,117.1(d,4JC-F＝3.3Hz),116.3(d,2JC-F＝18.6Hz),109.1,70.5,38.7,29.3,27.1.19FNMR(CDCl3,376MHz):δ-125.19--125.23(m).HRMS(ESI)m/z:[M+Na]+Calcd forC20H19FN2NaO 345.1374；Found 345.1366.
2-(tert-Butyl)-7-chloro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3p)
White solid(35mg,52％).1H NMR(CDCl3,600MHz):δ7.38(td,J1＝8.4Hz,J2＝1.2Hz,1H),7.31(d,J＝7.8Hz,1H),7.02-6.99(m,3H),6.77-6.76(m,1H),6.68(dd,J1＝7.2Hz,J2＝0.6Hz,1H),3.34(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,100MHz):δ188.1,171.6,153.2,144.6,141.6,129.54,129.50,127.2,126.3,125.6,124.2,123.4,119.7,109.1,71.1,38.8,29.4,27.2.HRMS(ESI)m/z:[M+Na]+Calcd for C20H19ClN2NaO 361.1078；Found 361.1062.
1'-Methyl-2-phenylspiro[indole-3,3'-indolin]-2'-one(3q)
White solid(37mg,57％).1H NMR(CDCl3,400MHz):δ7.78(d,J＝8.0Hz,1H),7.60-7.58(m,2H),7.43-7.33(m,3H),7.28-7.24(m,2H),7.17-7.13(m,1H),7.08(d,J＝8.0Hz,1H),6.98-6.93(m,2H),6.74(d,J＝7.2Hz,1H),3.40(s,3H).13C{1H}NMR(CDCl3,100MHz):δ174.2,172.4,156.4,144.4,140.1,132.2,131.2,129.4,129.3,128.8,128.0,127.8,126.7,123.9,123.8,121.7,121.4,109.2,69.0,27.3.HRMS(ESI)m/z:[M+H]+Calcd forC22H17N2O 325.1335；Found 325.1337.
5-Ethyl-1'-methyl-2-phenylspiro[indole-3,3'-indolin]-2'-one(3r)
White solid(26mg,37％).1H NMR(CDCl3,400MHz):δ7.61(d,J＝7.6Hz,1H),7.51-7.48(m,2H),7.32(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.26(t,J＝7.6Hz,1H),7.20-7.16(m,3H),7.02(d,J＝8.0Hz,1H),6.90(t,J＝7.6Hz,1H),6.70-6.68(m,2H),3.35(s,3H),2.51(q,J＝7.6Hz,2H),1.09(t,J＝7.6Hz,3H).13C{1H}NMR(CDCl3,100MHz):δ173.3,172.6,154.3,144.4,143.3,140.2,132.4,131.0,129.3,128.8,128.2,127.6,123.9,123.8,121.2,121.1,109.1,68.9,28.9,27.3,15.6.HRMS(ESI)m/z:[M+H]+Calcd for C24H21N2O353.1648；Found 353.1644.
1',6-Dimethyl-2-phenylspiro[indole-3,3'-indolin]-2'-one(3s)
White solid(30mg,44％).1H NMR(CDCl3,400MHz):δ7.61-7.57(m,3H),7.41-7.33(m,2H),7.28-7.24(m,2H),7.08(d,J＝8.0Hz,1H),6.97(t,J＝7.6Hz,2H),6.82(d,J＝7.6Hz,1H),6.75(d,J＝7.2Hz,1H),3.41(s,3H),2.43(s,3H).13C{1H}NMR(CDCl3,150MHz):δ174.3,172.6,156.7,144.3,139.5,137.1,132.3,131.1,129.3,128.8,128.2,127.7,127.4,123.9,123.7,122.2,121.3,109.1,68.7,27.3,21.7.HRMS(ESI)m/z:[M+H]+Calcdfor C23H19N2O 339.1492；Found 339.1494.
5-Chloro-2-(4-chlorophenyl)-1'-methylspiro[indole-3,3'-indolin]-2'-one(3t)
White solid(30mg,38％).1H NMR(CDCl3,400MHz):δ7.69(d,J＝8.4Hz,1H),7.50(d,J＝8.8Hz,2H),7.44(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.39(dd,J1＝8.4Hz,J2＝2.0Hz,1H),7.27-7.25(m,2H),7.10(d,J＝7.6Hz,1H),7.02(t,J＝7.6Hz,1H),6.91(d,J＝1.6Hz,1H),6.75(d,J＝7.2Hz,1H),3.42(s,3H).13C{1H}NMR(CDCl3,150MHz):δ173.4,171.4,154.7,144.2,141.4,137.8,132.5,130.3,130.0,129.7,129.2,129.0,126.8,124.1,124.0,122.4,122.3,109.4,68.9,27.4.HRMS(ESI)m/z:[M+Na]+Calcd for C22H14Cl2N2NaO415.0375；Found 415.0362.
2-(tert-Butyl)-1',5'-dimethylspiro[indole-3,3'-indolin]-2'-one(3u)
White solid(37mg,58％).1H NMR(CDCl3,400MHz):δ7.66(d,J＝7.6Hz,1H),7.36-7.32(m,1H),7.16(d,J＝7.6Hz,1H),7.09(t,J＝7.6Hz,1H),6.88(d,J＝8.0Hz,1H),6.80(d,J＝7.6Hz,1H),6.57(s,1H),3.32(s,3H),2.23(s,3H),1.17(s,9H).13C{1H}NMR(CDCl3,150MHz):δ187.3,172.2,156.1,142.4,139.9,132.9,129.5,128.9,126.9,126.2,124.7,121.4,120.6,108.7,70.2,38.5,29.4,27.1,21.0.HRMS(ESI)m/z:[M+H]+Calcd forC21H23N2O 319.1805；Found 319.1795.
2-(tert-Butyl)-5'-fluoro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3v)
White solid(40mg,62％).1H NMR(CDCl3,400MHz):δ7.66(d,J＝7.6Hz,1H),7.35(t,J＝7.6Hz,1H),7.12-7.05(m,2H),6.92(dd,J1＝8.8Hz,J2＝4.0Hz,1H),6.79(d,J＝7.2Hz,1H),6.52(dd,J1＝7.6Hz,J2＝2.4Hz,1H),3.33(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.4,171.9,159.3(d,1JC-F＝241.2Hz),156.2,140.7,139.3,129.2,128.6(d,3JC-F＝8.7Hz),126.3,121.3,120.8,115.6(d,2JC-F＝23.1Hz),112.1(d,2JC-F＝24.6Hz),109.5(d,3JC-F＝8.0Hz),70.1,38.5,29.4,27.2.19F NMR(CDCl3,376MHz):δ-119.1(td,J1＝8.6Hz,J2＝4.5Hz).HRMS(ESI)m/z:[M+Na]+Calcd for C20H19FN2NaO 345.1374；Found 345.1364.
2-(tert-Butyl)-5'-chloro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3w)
White solid(43mg,63％).1H NMR(CDCl3,400MHz):δ7.66(d,J＝7.6Hz,1H),7.38-7.33(m,2H),7.11(t,J＝7.6Hz,1H),6.92(d,J＝8.4Hz,1H),6.80(d,J＝7.6Hz,1H),6.75(d,J＝2.0Hz,1H),3.33(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.3,171.8,156.2,143.2,139.2,129.3,129.2,128.7,128.6,126.3,124.3,121.3,120.9,109.8,69.8,38.5,29.4,27.2.HRMS(ESI)m/z:[M+Na]+Calcd for C20H19ClN2NaO 361.1078；Found361.1068.
5'-Bromo-2-(tert-butyl)-1'-methylspiro[indole-3,3'-indolin]-2'-one(3x)
White solid(39mg,51％).1H NMR(CDCl3,400MHz):δ7.66(d,J＝7.6Hz,1H),7.49(dd,J1＝8.4Hz,J2＝1.6Hz,1H),7.36(t,J＝8.0Hz,1H),7.11(t,J＝7.6Hz,1H),6.88-6.86(m,2H),6.80(d,J＝7.6Hz,1H),3.33(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.3,171.7,156.2,143.7,139.2,132.1,129.3,129.1,127.1,126.4,121.3,120.9,115.7,110.3,69.7,38.5,29.4,27.2.HRMS(ESI)m/z:[M+H]+Calcd for C20H20BrN2O383.0754；Found 383.0750.
2-(tert-Butyl)-6'-methoxy-1'-methylspiro[indole-3,3'-indolin]-2'-one(3y)
White solid(38mg,57％).1H NMR(CDCl3,400MHz):δ7.65(d,J＝8.0Hz,1H),7.33(t,J＝7.6Hz,1H),7.08(t,J＝7.6Hz,1H),6.80(d,J＝7.6Hz,1H),6.66(d,J＝8.4Hz,1H),6.57(d,J＝2.4Hz,1H),6.49(dd,J1＝8.4Hz,J2＝2.4Hz,1H),3.85(s,3H),3.31(s,3H),1.17(s,9H).13C{1H}NMR(CDCl3,150MHz):δ187.4,172.8,161.0,155.9,146.0,140.0,128.9,126.2,124.8,121.3,120.6,118.3,107.0,97.0,69.6,55.6,38.4,29.3,27.1.HRMS(ESI)m/z:[M+H]+Calcd for C21H23N2O2 335.1754；Found 335.1740.
2-(tert-Butyl)-6'-chloro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3z)
White solid(46mg,68％).1H NMR(CDCl3,400MHz):δ7.66(d,J＝7.6Hz,1H),7.35(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.10(t,J＝7.6Hz,1H),7.01-6.97(m,2H),6.79(d,J＝7.2Hz,1H),6.68(d,J＝7.6Hz,1H),3.33(s,3H),1.17(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.5,172.2,156.2,145.8,139.3,135.0,129.2,126.3,125.4,125.0,123.1,121.2,120.8,109.7,69.5,38.5,29.4,27.2.HRMS(ESI)m/z:[M+H]+Calcd for C20H20ClN2O339.1259；Found 339.1254.
6'-Bromo-2-(tert-butyl)-1'-methylspiro[indole-3,3'-indolin]-2'-one(3aa)
White solid(50mg,65％).1H NMR(CDCl3,600MHz):δ7.65(d,J＝7.8Hz,1H),7.35(td,J1＝7.8Hz,J2＝0.6Hz,1H),7.15-7.13(m,2H),7.09(t,J＝7.8Hz,1H),6.78(d,J＝7.2Hz,1H),6.62(d,J＝7.8Hz,1H),3.32(s,3H),1.17(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.4,172.0,156.1,146.0,139.2,129.2,126.3,126.1,125.9,125.3,122.8,121.3,120.8,112.5,69.5,38.5,29.4,27.2.HRMS(ESI)m/z:[M+H]+Calcd for C20H20BrN2O383.0754；Found 383.0740.
2-(tert-Butyl)-1',7'-dimethylspiro[indole-3,3'-indolin]-2'-one(3bb)
White solid(40mg,63％).1H NMR(CDCl3,400MHz):δ7.65(d,J＝7.6Hz,1H),7.33(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.10-7.07(m,2H),6.86(d,J＝7.6Hz,1H),6.81(d,J＝8.0Hz,1H),6.54(d,J＝7.2Hz,1H),3.61(s,3H),2.67(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,100MHz):δ187.3,173.0,156.1,142.5,140.3,132.9,128.8,127.3,126.1,123.0,122.0,121.3,120.6,120.5,69.9,38.5,30.4,29.4,19.1.HRMS(ESI)m/z:[M+H]+Calcd forC21H23N2O 319.1805；Found 319.1796.
2-(tert-Butyl)-7'-chloro-1'-methylspiro[indole-3,3'-indolin]-2'-one(3cc)
White solid(42mg,62％).1H NMR(CDCl3,400MHz):δ7.66(d,J＝8.0Hz,1H),7.35(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.29(dd,J1＝8.4Hz,J2＝1.2Hz,1H),7.11(td,J1＝7.6Hz,J2＝0.8Hz,1H),6.89(t,J＝8.4Hz,1H),6.83(d,J＝7.2Hz,1H),6.61(dd,J1＝7.2Hz,J2＝1.2Hz,1H),3.71(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,150MHz):δ186.6,172.4,156.0,140.6,139.6,131.5,129.5,129.2,126.4,123.9,122.6,121.3,120.8,116.1,69.7,38.6,30.5,29.5.HRMS(ESI)m/z:[M+H]+Calcd for C20H20ClN2O 339.1259；Found 339.1246.
2-(tert-Butyl)-5'-chloro-1',7'-dimethylspiro[indole-3,3'-indolin]-2'-one(3dd)
White solid(40mg,57％).1H NMR(CDCl3,400MHz):δ7.65(d,J＝8.0Hz,1H),7.35(t,J＝7.6Hz,1H),7.12-7.08(m,2H),6.81(d,J＝7.6Hz,1H),6.53(d,J＝2.0Hz,1H),3.59(s,3H),2.64(s,3H),1.18(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.5,172.6,156.1,141.1,139.7,132.4,129.14,129.09,128.0,126.3,122.0,121.3,120.8,69.7,38.5,30.4,29.5,18.9.HRMS(ESI)m/z:[M+H]+Calcd for C21H22ClN2O 353.1415；Found 353.1405.
2-(tert-Butyl)-1'-isopropylspiro[indole-3,3'-indolin]-2'-one(3ee)
White solid(38mg,57％).1H NMR(CDCl3,600MHz):δ7.65(d,J＝7.8Hz,1H),7.35-7.31(m,2H),7.15(d,J＝7.8Hz,1H),7.08(td,J1＝7.8Hz,J2＝1.2Hz,1H),6.95(td,J1＝7.8Hz,J2＝0.6Hz,1H),6.77-6.74(m,2H),4.74-4.69(m,1H),1.58(d,J＝6.6Hz,3H),1.54(d,J＝7.2Hz,3H),1.20(s,9H).13C{1H}NMR(CDCl3,150MHz):δ187.3,171.6,156.1,143.4,140.3,128.83,128.80,127.4,126.1,124.4,122.5,121.0,120.6,110.5,70.3,44.5,38.4,29.4,19.5,18.8.HRMS(ESI)m/z:[M+H]+Calcd for C22H25N2O 333.1961；Found 333.1959.
1'-Benzyl-2-(tert-butyl)spiro[indole-3,3'-indolin]-2'-one(3ff)
White solid(41mg,54％).1H NMR(CDCl3,400MHz):δ7.67(d,J＝7.6Hz,1H),7.41(d,J＝7.6Hz,2H),7.38-7.31(m,4H),7.27-7.23(m,1H),7.11-7.08(m,1H),6.96-6.93(m,2H),6.76(t,J＝8.4Hz,2H),5.18(d,J＝15.2Hz,1H),4.84(d,J＝15.2Hz,1H),1.18(s,9H).13C{1H}NMR(CDCl3,100MHz):δ187.1,172.3,156.1,143.8,140.1,135.6,129.0,128.97,128.91,128.0,127.9,127.1,126.2,124.2,123.1,121.2,120.7,110.0,70.1,44.7,38.5,29.5.HRMS(ESI)m/z:[M+H]+Calcd for C26H25N2O 381.1961；Found 381.1951.
1'-Acetyl-2-(tert-butyl)spiro[indole-3,3'-indolin]-2'-one(3gg)
White solid(16mg,24％).1H NMR(CDCl3,400MHz):δ8.37(d,J＝8.0Hz,1H),7.69(d,J＝8.0Hz,1H),7.43-7.37(m,2H),7.13(t,J＝7.6Hz,2H),6.84(d,J＝7.6Hz,1H),6.77(dd,J1＝7.6Hz,J2＝0.8Hz,1H),2.68(s,3H),1.20(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.6,173.1,170.8,155.8,141.0,140.5,129.5,126.6,126.3,125.7,123.8,121.4,120.9,117.5,70.5,38.6,29.6,26.7.HRMS(ESI)m/z:[M+Na]+Calcd for C21H20N2NaO2355.1417；Found 355.1409.
1'-Benzoyl-2-(tert-butyl)spiro[indole-3,3'-indolin]-2'-one(3hh)
White solid(30mg,38％).1H NMR(CDCl3,400MHz):δ7.96(d,J＝8.4Hz,1H),7.75-7.72(m,2H),7.67(d,J＝8.0Hz,1H),7.56(t,J＝7.6Hz,1H),7.46-7.38(m,4H),7.21-7.14(m,2H),7.02(d,J＝7.6Hz,1H),6.85-6.83(m,1H),1.23(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.8,171.8,169.0,155.8,141.1,140.3,133.5,133.3,129.52,129.46,129.44,128.4,126.8,126.6,125.5,124.1,121.13,121.05,116.0,70.6,38.5,29.6.HRMS(ESI)m/z:[M+Na]+Calcd for C26H22N2NaO2 417.1573；Found 417.1567.
2-(tert-Butyl)-1'-tosylspiro[indole-3,3'-indolin]-2'-one(3ii)
White solid(40mg,45％),mp 241-242℃.1H NMR(CDCl3,400MHz):δ8.12(d,J＝8.4Hz,1H),7.99(d,J＝8.0Hz,2H),7.59(d,J＝7.6Hz,1H),7.42(t,J＝7.6Hz,1H),7.34-7.29(m,3H),7.08(t,J＝7.6Hz,1H),6.99(t,J＝7.6Hz,1H),6.69(d,J＝7.6Hz,1H),6.48(d,J＝7.2Hz,1H),2.44(s,3H),0.98(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.2,170.2,155.6,146.1,140.1,139.9,134.5,129.81,129.77,129.4,128.2,126.4,126.2,125.3,124.3,121.3,120.8,114.7,69.9,38.2,29.4,21.8.HRMS(ESI)m/z:[M+Na]+Calcd forC26H24N2NaO3S 467.1400；Found 467.1385.
tert-Butyl 2-(tert-butyl)-2'-oxospiro[indole-3,3'-indoline]-1'-carboxylate(3jj)
White solid(25mg,32％).1H NMR(CDCl3,400MHz):δ7.98(d,J＝8.4Hz,1H),7.65(d,J＝8.0Hz,1H),7.40-7.34(m,2H),7.13-7.06(m,2H),6.87(d,J＝7.2Hz,1H),6.74(dd,J1＝7.6Hz,J2＝1.2Hz,1H),1.64(s,9H),1.20(s,9H).13C{1H}NMR(CDCl3,100MHz):δ186.9,170.0,155.8,149.1,140.7,140.6,129.33,129.26,126.4,126.0,124.9,124.0,121.6,120.7,115.8,85.0,70.5,38.5,29.5,28.1.HRMS(ESI)m/z:[M+H]+Calcd for C24H27N2O3391.2016；Found 391.2010.
实施例4
本发明所合成的产物3-吲哚酮[螺]-3H-吲哚类化合物3进行一系列反应，从而合成进一步的衍生物。例如：
Figure BDA0003068056630000131
将3a(60.9mg，0.2mmol)、硼氢化钠(15.1mg，0.4mmol)和苯甲酸(48.8mg，0.4mmol)混合物在室温下用研钵研磨15分钟。饱和NaHCO3溶液淬灭，并用CH2Cl2(10mL×3)萃取，合并有机相。水洗，有机相无水Na2SO4干燥，过滤减压浓缩。硅胶柱分离(石油醚/乙酸乙酯＝20/1)得到黄色固体产物4a(36mg，59％)。1H NMR(400MHz,CDCl3):δ7.32(td,J1＝7.6Hz,J2＝0.8Hz,1H),7.22(d,J＝7.2Hz,1H),7.11-7.06(m,2H),6.87-6.84(m,2H),6.65(t,J＝7.6Hz,1H),6.44(d,J＝7.6Hz,1H),4.13(s,1H),4.02(s,1H),3.24(s,3H),0.88(s,9H).13C{1H}NMR(CDCl3,100MHz):δ176.2,151.1,144.2,133.6,132.0,128.8,128.4,124.0,123.1,122.7,119.8,111.1,107.8,80.5,59.3,34.2,28.0,26.4.HRMS(ESI)m/z:[M+H]+Calcd forC20H23N2O 307.1805；Found 307.1800.
Figure BDA0003068056630000141
将LiAlH4(75.9mg，2.0mmol)加入到25mL两颈瓶中，再进行三次抽真空、充氩气，在氩气和0℃下，将3a(60.9mg，0.2mmol)/无水THF(2mL)溶液滴加到两颈瓶中。然后将反应混合物升至室温，并在室温继续搅拌4小时。反应结束后，饱和NaHCO3溶液淬灭，过滤乙酸乙酯(10mL×3)萃取。合并有机层，水洗，无水Na2SO4干燥，过滤减压浓缩。硅胶柱分离(石油醚/乙酸乙酯＝30/1)得到白色固体产物5a(27mg，46％)。1H NMR(CDCl3,400MHz):δ7.95(s,1H),7.30-7.25(m,2H),7.22-7.17(m,2H),7.13(td,J1＝8.0Hz,J2＝1.2Hz,1H),7.03-6.98(m,2H),6.93(td,J1＝7.6Hz,J2＝1.2Hz,1H),2.48(s,6H),1.27(s,9H).13C{1H}NMR(CDCl3,100MHz):δ153.4,141.8,134.5,133.9,130.4,129.3,127.7,121.3,120.3,119.38,119.36,117.2,112.0,109.8,42.9,33.5,30.1.HRMS(ESI)m/z:[M+H]+Calcd for C20H25N2293.2012；Found 293.2011.
Figure BDA0003068056630000142
将Na2CO3(12.7mg，0.12mmol)/H2O(2mL)溶液加入到3jj(39mg，0.1mmol)/DME(2mL)溶液中，并将混合物置于100℃油浴中回流搅拌15分钟。反应结束后，冷却至室温，并用CH2Cl2(10mL×3)萃取。合并后有机层水洗，无水Na2SO4干燥，过滤减压浓缩。硅胶柱分离(石油醚/乙酸乙酯＝30/1)得到白色固体产物6a(20mg，76％)。1H NMR(CDCl3,400MHz):δ8.11(s,1H),7.36(d,J＝8.0Hz,1H),7.22-7.14(m,4H),7.03(t,J＝7.6Hz,1H),6.82-6.78(m,2H),3.57(s,2H),1.34(s,9H).13C{1H}NMR(CDCl3,150MHz):δ145.7,143.9,134.3,132.9,129.5,128.3,121.8,121.6,119.7,119.0,117.9,114.7,110.2,108.8,33.3,30.4.HRMS(ESI)m/z:[M+H]+Calcd for C18H21N2 265.1699；Found 265.1685.
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 (10)

1.一种3-吲哚酮[螺]-3H-吲哚类化合物3的合成方法，其特征在于，包括如下操作：将N-芳基脒类化合物1、重氮吲哚酮类化合物2、铑或钌催化剂、酸性添加剂和有机溶剂混合，升温反应得到3-吲哚酮[螺]-3H-吲哚类化合物3；反应方程式为：
Figure FDA0003068056620000011
其中R1为氢、卤素、三氟甲基、C1-4烷基、C1-4烷氧基或苄氧基，R2为C1-4烷基、苯基或取代苯基，取代苯基苯环上的取代基为卤素、C1-4烷基或C1-4烷氧基，R3为氢、卤素、C1-4烷基或C1-4烷氧基，R4为C1-4烷基、苄基、C1-4烷基酰基、磺酰基、叔丁氧羰基或芳基甲酰基。
2.根据权利要求1所述3-吲哚酮[螺]-3H-吲哚类化合物3的合成方法，其特征在于：反应溶剂为1,2-二氯乙烷、甲醇、丙酮、四氢呋喃、乙腈或甲苯。
3.根据权利要求1所述3-吲哚酮[螺]-3H-吲哚类化合物3的合成方法，其特征在于：所述酸性添加剂为醋酸、三甲基乙酸、苯甲酸、2,4,6-三甲基苯甲酸或1-金刚烷甲酸。
4.根据权利要求1所述3-吲哚酮[螺]-3H-吲哚类化合物的合成方法，其特征在于：所述催化剂为[RhCp*Cl2]2或[Ru(p-cymene)Cl2]2。
5.根据权利要求1所述3-吲哚酮[螺]-3H-吲哚类化合物的合成方法，其特征在于：所述反应温度为0-100℃。
6.根据权利要求1所述3-吲哚酮[螺]-3H-吲哚类化合物3的合成方法，其特征在于：所述N-芳基脒类化合物1、重氮吲哚酮类化合物2、酸性添加剂与催化剂摩尔比为1:1-2:0.5-2:0.02-0.06。
7.根据权利要求1所述3-吲哚酮[螺]-3H-吲哚类化合物3的合成方法，其特征在于：反应在空气氛围下进行。
8.一种合成3-吲哚醇[螺]-3H-吲哚类化合物4的方法，其特征在于，包括如下步骤：采用权利要求1-7任意一项所述方法合成3-吲哚酮[螺]-3H-吲哚类化合物3，接着3-吲哚酮[螺]-3H-吲哚类化合物3在苯甲酸存在下与硼氢化钠反应，得到吲哚类化合物4，结构通式为
Figure FDA0003068056620000012
其中R1-R4同权利要求1中一致。
9.一种合成吲哚类化合物5的方法，其特征在于，包括如下步骤：采用权利要求1-7任意一项所述方法合成3-吲哚酮[螺]-3H-吲哚类化合物3，接着3-吲哚酮[螺]-3H-吲哚类化合物3在四氢铝锂存在下反应，得到吲哚类化合物5，结构通式为
Figure FDA0003068056620000021
其中R1-R4同权利要求1中一致。
10.一种合成吲哚类化合物6的方法，其特征在于，包括如下步骤：采用权利要求1-7任意一项所述方法合成3-吲哚酮[螺]-3H-吲哚类化合物3，接着3-吲哚酮[螺]-3H-吲哚类化合物3，对应R4＝Boc时，在碳酸钠存在下反应，得到吲哚类化合物6，结构通式为
Figure FDA0003068056620000022
其中R1-R3同权利要求1中一致。
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