CN110964020B - Method for preparing 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] compound - Google Patents
Method for preparing 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] compound Download PDFInfo
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- CN110964020B CN110964020B CN201811140270.7A CN201811140270A CN110964020B CN 110964020 B CN110964020 B CN 110964020B CN 201811140270 A CN201811140270 A CN 201811140270A CN 110964020 B CN110964020 B CN 110964020B
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
The invention relates to a method for preparing 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] derivatives. In particular to a method for preparing 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] derivatives by 3-diazoindoline compounds and ethylene azide compounds under the action of transition metals. The method provided by the invention is used for preparing the 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] derivative from simple and easily available raw materials through simple operation steps.
Description
Technical Field
The invention relates to a method for preparing a 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] compound.
Background
Spiro heterocyclic compounds are common frameworks in natural products, drug molecules and many types of catalysts, and indole spiro pyrrole compounds are a very important type of them as a general synthetic module. Various spiro [ indoline-3, 2' -pyrroles ] have interesting structural properties and highly potent pharmacological activities, including anticancer activity, cholinesterase inhibitors, advanced glycosylation end product activity, antibacterial activity and antidiabetic activity. Its biological activity should be related to the spiro assembly of its two part important modules. Based on their activities, various synthetic methods have been reported in recent years, including 1, 3-dipolar cycloaddition, nucleophilic addition, intramolecular hydroamination, homoenol addition, Buchwald-Hartwig/Michael reaction, aromatization, reductive cyclization, etc., but at present, no method for providing a pyrrole ring structure by a domino reaction with an azidoalkenyl group has been reported. A simple one-step process for preparing 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] compounds from 3-diazoindoline compounds and vinyl azides is described.
Disclosure of Invention
The invention aims to provide a method for synthesizing a 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] compound.
Reaction equation 1: the specific operation steps for synthesizing the 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] compound are as follows (reaction equation 1):
reacting in a reactor, adding 3-diazoindoline 1 and vinyl azide 2, then adding a solvent and a catalyst, and reacting at 0-100 ℃, preferably 60 ℃ for 12-36 hours, preferably 24 hours; after the reaction is finished, separating to obtain the 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] compound 3.
The molar ratio of the vinyl azide 2 to the 3-diazoindoline 1 is 1-10:1, and the preferred ratio is 7: 1.
The catalyst being Rh2(OAc)4、Rh2(Oct)4、Rh2(TFA)4、Rh2(OAc)4One or more of rhodium octanoate, rhodium (II) hexanoate dimer, rhodium (II) tetrakis (triphenylacetate) dichlormethane adduct, and rhodium (II) trimethylacetate dimer, preferably Rh2(TFA)4(ii) a The amount of the catalyst is 0 to 100mol percent, preferably 5mol percent of the amount of the 3-diazoindoline 1.
The solvent is one or more of 1, 2-dichloroethane, dichloromethane, chloroform, 1,2, 2-tetrachloroethane, chlorobenzene, trifluorotoluene, 1, 4-dioxane and toluene, preferably 1, 2-dichloroethane; the amount of solvent used is 5 to 50 ml, preferably 10 ml, per mmol of 3-diazoindoline 1.
The invention has the following advantages:
1. the synthesis process of the reactants is simple and only needs one to two steps.
2. The reaction is simple and convenient to operate, and compared with the traditional method, the reaction product can be obtained in one step.
3. The reaction yield is high.
Detailed Description
For a better understanding of the present invention, the following examples are set forth.
Reacting in a reactor, adding 3-diazoindoline 1(0.3mmol) and ethylene azide 2(7eq.), and then adding Rh2(TFA)4(5 mol%) and 1, 2-dichloroethane (3mL) at 60 ℃ for 24 hours. After the reaction is finished, the solvent is pumped out, the crude sample is dissolved in dichloromethane and loaded for silica gel column chromatography, and the 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole can be obtained]Compound 3.
The reaction materials and results of examples 1-3 are shown in Table 1.
TABLE 1
The characterization data for the products of examples 1-3 are as follows:
1-benzyl-5′-phenyl-3′,4′-dihydrospiro[indoline-3,2′-pyrrol]-2-one：
1H NMR(400 MHz,CDCl3)δ7.94–7.91(m,2H),7.47–7.40(m,3H),7.35–7.29(m,4H),7.27–7.23(m,1H),7.19–7.13(m,2H),7.02–6.98(dd,J＝11.0,4.0 Hz,1H),6.74(d,J＝7.8 Hz,1H),5.02(d,J＝15.7 Hz,1H),4.83(d,J＝15.7 Hz,1H),3.50(ddd,J＝16.8,9.5,7.2 Hz,1H),3.38(ddd,J＝17.0,9.7,4.9 Hz,1H),2.67(ddd,J＝13.4,9.5,4.9 Hz,1H),2.31(ddd,J＝13.1,9.7,7.2 Hz,1H).；13C NMR(101 MHz,CDCl3)δ177.57,177.43,142.87,135.80,133.86,132.31,131.22,129.16,128.87,128.50,128.40,127.67,127.41,123.75,123.17,109.42,81.62,44.04,36.84,33.22.
5′-phenyl-1-tosyl-3′,4′-dihydrospiro[indoline-3,2′-pyrrol]-2-one：
1H NMR(400 MHz,CDCl3)δ8.00(d,J＝8.4 Hz,2H),7.95(d,J＝8.2 Hz,1H),7.84–7.82(m,2H),7.48–7.45(m,1H),7.41–7.36(m,3H),7.31(d,J＝8.1 Hz,2H),7.20–7.12(m,2H),3.44–3.29(m,2H),2.61(ddd,J＝13.4,8.8,4.7 Hz,1H),2.41(s,3H),2.21(ddd,J＝13.4,9.4,8.3 Hz,1H).；13C NMR(101 MHz,CDCl3)δ178.75,175.43,145.81,139.04,135.26,133.41,131.61,131.24,129.97,129.93,128.61,128.45,128.12,125.49,124.16,113.85,81.64,36.59,34.73,21.83.
1-benzoyl-5′-phenyl-3′,4′-dihydrospiro[indoline-3,2′-pyrrol]-2-one：
1H NMR(400 MHz,CDCl3)δ7.95–7.89(m,3H),7.77–7.75(m,2H),7.57–7.53(m,1H),7.49–7.39(m,6H),7.24(d,J＝3.7 Hz,2H),3.47–3.33(m,2H),2.67(ddd,J＝13.7,8.4,5.4 Hz,1H),2.38–2.30(m,1H).；13C NMR(101 MHz,CDCl3)δ178.00,176.99,169.46,140.18,134.24,133.58,132.89,131.79,131.54,129.69,129.48,128.64,128.46,128.30,125.66,123.92,115.50,82.13,36.98,33.87.
comparative example 1:
the operation process is the same as that of example 1, except that the catalyst is PPh3AuCl/AgSbF6(1/1, 3 mol%) and yield of product 3 was 0%.
Comparative example 2:
the procedure was as in example 1, except that in example 1, the yield of product 3 was 0% without using any catalyst.
Claims (5)
1. A process for preparing a 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] derivative, characterized in that:
3-diazo dihydro indoline compound 1 and vinyl azide compound 2 shown in the following formula are taken as raw materials to generate 3 ', 4 ' -dihydro spiro [ indoline-3, 2 ' -pyrrole ] derivative 3, and the reaction formula is as follows:
R2selected from fluorine, chlorine, bromine, trifluoromethyl, C1-C5 alkyl, R1Selected from arylsulfonyl, R3Selected from unsubstituted phenyl; the specific operation steps are as follows:
reacting in a reactor, adding 3-diazo dihydro indoline compound 1 and vinyl azide compound 2, then adding solvent and catalyst, and reacting at 60-100 ℃; reacting for 12-36 hours; after the reaction is finished, separating to obtain a 3 ', 4 ' -dihydrospiro [ indoline-3, 2 ' -pyrrole ] derivative 3;
the catalyst being Rh2(TFA)4(ii) a The dosage of the catalyst is 0 to 5mol percent of that of the 3-diazo dihydro indoline compound 1 and is not 0.
2. The method of claim 1, wherein:
the molar ratio of the vinyl azide compound 2 to the 3-diazo dihydro indoline compound 1 is 1-50: 1.
3. A method as claimed in claim 2, characterized in that: the molar ratio of the vinyl azide compound 2 to the 3-diazo dihydro indoline compound 1 is 7: 1.
4. The method of claim 1, wherein:
the solvent is one or more than two of 1, 2-dichloroethane, dichloromethane, chloroform, 1,2, 2-tetrachloroethane, chlorobenzene, trifluorotoluene, 1, 4-dioxane and toluene; the amount of the solvent is 5-50 ml per millimole of the 3-diazo dihydro indoline compound 1.
5. The method of claim 4, wherein:
the solvent is 1, 2-dichloroethane; the amount of the solvent used was 10 ml per mmol of the 3-diazo dihydroindoline compound 1.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080125430A1 (en) * | 2006-08-30 | 2008-05-29 | The Regents Of The University Of Michigan | New small molecule inhibitors of mdm2 and the uses thereof |
| WO2009143156A2 (en) * | 2008-05-19 | 2009-11-26 | Sepracor Inc. | IMIDAZO[1,2-a]PYRIDINE COMPOUNDS |
| CN102268000A (en) * | 2011-05-05 | 2011-12-07 | 温州医学院 | Novel spiroheterocyclic compound and application of same serving as therapeutic agent |
| CN102659786A (en) * | 2012-04-16 | 2012-09-12 | 上海大学 | 6a,7-dihydro-m-diaza naphthalene [1,2-a]-quinazoline-5,8(6H)-diketone and preparation method thereof |
| CN103483344A (en) * | 2013-09-11 | 2014-01-01 | 常州大学 | Method for synthesizing oxindole spiro compound |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080125430A1 (en) * | 2006-08-30 | 2008-05-29 | The Regents Of The University Of Michigan | New small molecule inhibitors of mdm2 and the uses thereof |
| WO2009143156A2 (en) * | 2008-05-19 | 2009-11-26 | Sepracor Inc. | IMIDAZO[1,2-a]PYRIDINE COMPOUNDS |
| CN102268000A (en) * | 2011-05-05 | 2011-12-07 | 温州医学院 | Novel spiroheterocyclic compound and application of same serving as therapeutic agent |
| CN102659786A (en) * | 2012-04-16 | 2012-09-12 | 上海大学 | 6a,7-dihydro-m-diaza naphthalene [1,2-a]-quinazoline-5,8(6H)-diketone and preparation method thereof |
| CN103483344A (en) * | 2013-09-11 | 2014-01-01 | 常州大学 | Method for synthesizing oxindole spiro compound |
Non-Patent Citations (2)
| Title |
|---|
| "[1+1+3] Annulation of Diazoenals and Vinyl Azides: Direct Synthesis of Functionalized 1-Pyrrolines through Olefination"及其Supporting Information;Vinaykumar Kanchupalli等，;《Angew. Chem. Int. Ed.》;20180406(第57期);第5433–5437页及其Supporting Information第S1-S52页 * |
| "Construction of 1-pyrroline skeletons by Lewis acid-mediated conjugate addition of vinyl azides"及其Electronic Supplementary Information;Xu Zhu等，;《Chem. Commun.》;20160104(第52期);第2473-2476页及其Electronic Supplementary Information第S1-S37页 * |
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