CN108003086A - A kind of preparation method of 3- amidos -2- indole ketone compounds - Google Patents
A kind of preparation method of 3- amidos -2- indole ketone compounds Download PDFInfo
- Publication number
- CN108003086A CN108003086A CN201711246143.0A CN201711246143A CN108003086A CN 108003086 A CN108003086 A CN 108003086A CN 201711246143 A CN201711246143 A CN 201711246143A CN 108003086 A CN108003086 A CN 108003086A
- Authority
- CN
- China
- Prior art keywords
- reaction
- alkyl
- aryl
- heteroaryl
- indole ketone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 0 CC(C)C*(CC(*)*)[C@](CC=C)(C(*1)=O)c2c1cccc2 Chemical compound CC(C)C*(CC(*)*)[C@](CC=C)(C(*1)=O)c2c1cccc2 0.000 description 8
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The present invention provides a kind of green synthesis method of simple, Cheap highly effective 3 amido of preparation, 2 indole ketone compound of technique, and this method is using 2 indole ketone compound 1a and amine 2a as raw material, in I2Under TBHP systems, aminating reaction occurs under the conditions of 60 DEG C, easily and with excellent yield prepares 3 amido, 2 indole ketone compound 1.Its reaction equation is as follows：
Description
Technical field
The present invention relates to a kind of I2- TBHP without 2- indole ketone compound C (sp under metallic green catalyst system and catalyzing3)-H amine
Change method, more particularly to one kind using 2- indolone derivatives and amine as raw material, in I2Occur under-TBHP systems, under the conditions of 60 DEG C
Aminating reaction, the method for preparing 3- amido -2- indole ketone compounds.
Background technology
Indolone skeleton causes chemist and biologist is extensive and long-term because of its unique design feature and physiological activity
Concern.And an important subclass of the 3- amido -2- indolones as indolone skeleton, it is widely present in natural products and biology
In bioactive molecule, wherein more representational have following several (seeing below formula one)：
Since 3- amido -2- indole ketone compounds and its derivative are very important organic intermediate, and it is many
Native compound all contains these skeletons, it is shown with good pharmaceutical activity, in medicine, biology etc. application very
Extensively.Therefore, development is convenient, environmental-friendly, be efficiently synthesized 3- amido -2- indolones and its method for derivative seems suitable
It is important.
Inventor has found that the route of synthesis of synthetically prepared 3- amidos -2- indole ketone compounds mainly wraps in the prior art
Include：The α-arylation reaction of acid amides, the alkylated reaction of 3- amido indoles, nucleophilic addition, the Mannich of imines
Addition reaction.In recent years, also there is researcher have developed and prepare 3- amido -2- Yin by raw material of 2- indole ketone compounds
The method of diindyl ketone compounds.For example, reference can be made to following document：
(1)“A Catalytic Metal-Free Ritter Reaction to 3-Substituted 3-
Aminooxindoles ", Feng Zhou et.al., Org.Biomol.Chem., 2012,10,3178；
(2)“Synthesis of 3-Amino-3-hydroxymethyloxindoles and 3-Hydroxy-3-
hydroxymethyloxindoles by Rh2(OAc)4-Catalyzed Three-Component Reactions of 3-
Diazooxindoles with Formaldehyde and Anilines or Water ", Chengjin Wang et.al.,
J.Org.Chem.2014,79,3908-3916；
(3)“Facile and Efficient Enantioselective Hydroxyamination Reaction：
Synthesis of 3-Hydroxyamino-2-Oxindoles Using Nitrosoarenes ", Ke Shen et.al.,
Angew.Chem.Int.Ed.2011,50,4684-4688.
However, the 2- indole ketone compounds in these prior arts report prepare 3- amido -2- indole ketones for raw material
In compound method, its reaction condition is more harsh and reaction cost is high, such as using strong acid such as perchloric acid, and/or using expensive
Expensive catalyst system and catalyzing such as metal rhodium, nitrogen ligand etc..Therefore, a kind of more efficient, more cheap, more green synthesis side is found
Method is still the problem of a challenge.
The content of the invention
Present invention aims to overcome that the deficiencies in the prior art, there is provided a kind of technique is simple, the preparation 3- amine of high efficiency low cost
The green synthesis method of base -2- indole ketone compounds, this method is using 2- indole ketone compounds and amine as raw material, in I2-
In TBHP systems, under the conditions of 60 DEG C, easily and with excellent yield 3- amido 2- indole ketone compounds are prepared.
The preparation method of 3- amidos -2- indole ketone compounds provided by the invention, this method is with 2- indole ketone chemical combination
Thing is raw material, is prepared through the following steps：
Added into Schlenk reaction bulbs 2- indolone derivatives (1a), the aminated compounds shown in formula 2a, catalyst,
Oxidant and organic solvent, are placed in 60 DEG C, stirring is reacted in oil bath under the conditions of air atmosphere by reaction bulb, are supervised through TLC or GC
Reaction process is surveyed, the reaction was complete to raw material, post-treated to obtain target product 3- amido 2- indole ketone compounds (I).
The preparation method of 3- amidos -2- indole ketone compounds provided by the invention, its chemical equation can be expressed as (see
Formula two)：
In above-mentioned reaction, the organic solvent may be selected from one in dichloroethanes, dichloromethane, acetonitrile, tetrahydrofuran
Kind is several, is preferably the dichloroethanes of above-mentioned solvent.
The post-processing operation is as follows：Reaction solution after the completion of reaction is concentrated under reduced pressure, by residue through column chromatography point
From (eluting solvent is：Ethyl acetate/n-hexane) obtain target product 3- amido -2- indole ketone compounds (I).
The product 3- amido -2- indole ketones that the raw material 2- indole ketone compounds and Formulas I that above-mentioned formula 1a is represented represent
In compound, R1Represent one or more substituents, each R on its phenyl ring connected1It is independently from each other hydrogen, C1-C6Alkyl,
C1-C6Alkoxy, C1-C6Acyl group, C1-C6Ester group, halogen, cyano group, nitro, C3-C6Cycloalkyl, C5-C14Aryl, C5-C14Heteroaryl
Base ,-NRaRb.Wherein, Ra, RbIt is independently from each other C1-C6Alkyl or hydrogen；The hetero atom of the heteroaryl is selected from O, S or N.
R2Represent hydrogen, C1-C6Alkyl, halogen, cyano group, C3-C6Cycloalkyl, C5-C14Aryl, C5-C14Heteroaryl；The heteroaryl
The hetero atom of base is selected from O, S or N.
R3Represent hydrogen, tertbutyloxycarbonyl (Boc), C1-C6Alkyl, C1-C6Acyl group, C3-C6Cycloalkyl, C5-C14Aryl, C5-
C14Aryl-C1-C6Alkyl, C5-C14Heteroaryl, the hetero atom of the heteroaryl are selected from O, S or N.
Wherein, above-mentioned each alkyl, alkoxy, cycloalkyl, aryl and heteroaryl can be further substituted with a substituent, institute
The substituent stated is selected from halogen or C1-C6Alkyl.
Preferably, R1Represent one or more substituents, each R on its phenyl ring connected1Be independently from each other hydrogen,
C1-C6Alkyl, halogen, C1-C6Alkoxy, nitro, C5-C14Aryl；Wherein described C1-C6Alkyl and/or C5-C14Aryl can be into
One step is substituted, and the substituent is selected from halogen or C1-C6Alkyl.
Preferably, R2Represent hydrogen, C1-C6Alkyl, halogen, cyano group, C5-C14Aryl, wherein the C1-C6Alkyl and/or C5-
C14Aryl can be further substituted, and the substituent is selected from halogen or C1-C6Alkyl.
Preferably, R3Represent hydrogen, tertbutyloxycarbonyl (Boc), C1-C6Alkyl, C1-C6Acyl group, phenyl, benzyl, wherein described
C1-C6Alkyl and/or C1-C6Acyl group, phenyl and/or benzyl can be further substituted, and the substituent is selected from halogen or C1-C6
Alkyl.
In the compound that above-mentioned formula 2a is represented, various aminated compounds are represented.The addition of the compound of formula 2a is preferably
150~the 300mol% of 2- indolone derivatives (1a) addition, is most preferably 2- indolone derivatives (1a) addition
200mol%.
Wherein, the TBHP in above-mentioned and this specification described in other parts belongs to chemical substance contracting well known in the art
Form is write, it is tertbutanol peroxide, and English name is tert-Butyl hydroperoxide.
The beneficial effects of the invention are as follows：Propose a kind of new method for preparing 3- amido -2- indole ketone compounds, the party
Method is using 2- indole ketone compounds and amine as reaction raw materials, in I2In-TBHP systems, C (sp occur under the conditions of 60 DEG C3)-H aminations
Reaction, to obtain a series of target product in high yield.This method without using acid, without using metallic catalyst, without using ligand,
Reaction atmosphere is air, has the advantages that reaction substrate accommodation is extensive, simple efficient, economic and environment-friendly, particularly suitable for work
Industry metaplasia is produced.
Brief description of the drawings
Fig. 1 is the nucleus magnetic hydrogen spectrum figure of product 3- morpholino -3- phenyl -2- indolones.
Fig. 2 is the nuclear-magnetism carbon spectrogram of product 3- morpholino -3- phenyl -2- indolones.
Fig. 3 is the mechanism schematic diagram that the present invention reacts.
Embodiment
Below in conjunction with specific embodiment, further detailed description is carried out to the present invention.
1 compound of embodimentSynthesis
Add into the Schlenk reaction bulbs that volume is 20mL the 3- phenyl -2- indolones of 0.3mmol, 0.6mmol
The I of quinoline, 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, under the conditions of air atmosphere
Stirring reaction, reaction process is monitored through TLC or GC, and the reaction was complete to raw material when small (4), and the reaction solution after the completion of reaction is depressurized
Concentration, by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/n-hexane) obtain target product 3- morpholinoes -3-
Phenyl -2- indolones.
White solid (83%yield)；1H NMR (400MHz, CDCl3)δ：7.92 (s, 1H), 7.58 (d, J=8.0Hz,
2H), 7.36-7.29 (m, 4H), 7.24 (d, J=8.0Hz, 1H), 7.06 (t, J=7.6Hz, 1H), 6.89 (d, J=7.6Hz,
1H), 3.71 (t, J=4.4Hz, 4H), 2.64 (t, J=4.4Hz, 4H)；13C NMR (100MHz, CDCl3)δ：177.3
140.4,138.1,129.3,129.0,128.7,128.1,127.6,126.3,122.8,110.1,74.4,67.5,47.6；
HRMS m/z(ESI)calcd for C18H19N2O2([M+H]+) 295.1441, found 295.1443.
Embodiment 2 replaces I with catalyst tetrabutylammonium iodide2, remaining condition is with embodiment 1, target product yield
60%.
Embodiment 3 replaces I with catalyst tetrabutylammonium bromide2, remaining condition is the same as embodiment 1, target product yield ＜
5%.
Embodiment 4 replaces TBHP with oxidant di-t-butyl peroxide, remaining condition is the same as embodiment 1, target product yield
For 51%.
Embodiment 5 replaces TBHP with oxidant benzoyl peroxide, remaining condition is with embodiment 1, target product yield
56%.
Embodiment 6 replaces dichloroethanes with methylene chloride, remaining condition is with embodiment 1, target product yield
68%.
Embodiment 7 replaces dichloroethanes with solvent acetonitrile, remaining condition is the same as embodiment 1, target product yield 70%.
Embodiment 8 replaces dichloroethanes with solvents tetrahydrofurane, remaining condition is with embodiment 1, target product yield
45%.
It is nitrogen atmosphere (1atm) that embodiment 9, which adjusts reaction atmosphere, remaining condition is with embodiment 1, target product yield
81%.
10 compound of embodimentSynthesis
3- phenyl -2- the indolones of addition 0.3mmol, the two of 0.6mmol into the Schlenk reaction bulbs that volume is 20mL
The I of hydrogen indoles, 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, air atmosphere bar
Reaction is stirred under part, reaction process is monitored through TLC or GC, the reaction was complete to raw material when small (4), by the reaction solution after the completion of reaction
It is concentrated under reduced pressure, by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
Black liquor (70%yield)；1H NMR (400MHz, CDCl3)δ：8.76 (s, 1H), 7.59 (d, J=7.2Hz,
2H), 7.34 (t, J=5.6Hz, 4H), 7.25-7.19 (m, 1H), 7.04 (d, J=7.2Hz, 1H), 6.96 (t, J=7.6Hz,
1H), 6.89 (d, J=7.6Hz, 1H), 6.75 (t, J=7.6Hz, 1H), 6.65 (t, J=7.6Hz, 1H), 5.99 (d, J=
8.0Hz, 1H), 3.52 (t, J=10.4Hz, 1H), 3.05 (t, J=8.8Hz, 1H), 2.95 (t, J=10.0Hz, 1H), 2.85
(t, J=8.8Hz, 1H)；13C NMR (100MHz, CDCl3)δ：177.3,149.4,140.9,138.1,131.7,129.6,
129.3,128.8,128.5,126.4,126.2,124.7,123.1,119.0,115.3,111.7,110.3,71.8,50.8,
28.1；HRMS m/z(ESI)calcd for C22H19N2O([M+H]+) 327.1492, found 327.1496.
11 compound of embodimentSynthesis
3- phenyl -2- indolones, the N- of 0.6mmol of 0.3mmol is added into the Schlenk reaction bulbs that volume is 20mL
The I of methylbenzylamine, 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, air atmosphere
Under the conditions of stir reaction, monitor reaction process through TLC or GC, the reaction was complete to raw material when small (4), by the reaction after the completion of reaction
Liquid is concentrated under reduced pressure, and by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
Light yellow liquid (73%yield)；1H NMR (400MHz, CDCl3)δ：9.00 (s, 1H), 7.71 (d, J=
8.0Hz, 2H), 7.42 (d, J=7.6Hz, 3H), 7.33-7.21 (m, 7H), 7.07 (t, J=7.6Hz, 1H), 6.93 (d, J=
7.6Hz, 1H), 3.75-3.64 (m, 2H), 2.16 (s, 3H)；13C NMR (100MHz, CDCl3)δ：178.8,140.7,139.6,
139.5,130.1,128.8,128.6,128.4,128.2,128.1,127.5,126.8,125.9,122.7,110.4,75.1,
55.7 35.9；HRMS m/z(ESI)calcd for C22H21N2O([M+H]+) 329.1648, found 329.1644.
12 compound of embodimentSynthesis
3- phenyl -2- indolones, the N- of 0.6mmol of 0.3mmol is added into the Schlenk reaction bulbs that volume is 20mL
The I of methylaniline, 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, air atmosphere
Under the conditions of stir reaction, monitor reaction process through TLC or GC, the reaction was complete to raw material when small (4), by the reaction after the completion of reaction
Liquid is concentrated under reduced pressure, and by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
White solid (55%yield)；1H NMR (400MHz, CDCl3)δ：8.12 (s, 1H), 7.59 (d, J=7.6Hz,
2H), 7.37-7.27 (m, 5H), 7.06-7.02 (m, 3H), 6.95 (d, J=8.0Hz, 2H), 6.87 (t, J=7.6Hz, 1H),
6.78 (d, J=8.0Hz, 1H), 2.92 (s, 3H)；13C NMR (100MHz, CDCl3)δ：178.3,149.4,140.0,139.2,
130.6,128.9,128.5,128.2,128.1,127.8,126.3,124.0,122.8,122.6,110.2,74.2,39.3；
HRMS m/z(ESI)calcd for C21H19N2O([M+H]+) 315.1492, found 315.1488.
13 compound of embodimentSynthesis
3- phenyl -2- indolones, the benzene of 0.6mmol of 0.3mmol is added into the Schlenk reaction bulbs that volume is 20mL
The I of amine, 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, under the conditions of air atmosphere
Stirring reaction, reaction process is monitored through TLC or GC, and the reaction was complete to raw material when small (4), and the reaction solution after the completion of reaction is depressurized
Concentration, by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
White solid (83%yield)；1H NMR (400MHz, CDCl3)δ：8.44 (s, 1H), 7.57 (d, J=8.0Hz,
2H), 7.35 (d, J=6.8Hz, 4H), 7.25 (t, J=8.0Hz, 1H), 7.07-6.98 (m, 3H), 6.90 (d, J=7.6Hz,
1H), 6.69 (t, J=7.2Hz, 1H), 6.41 (d, J=8.0Hz, 2H), 4.65 (s, 1H)；13C NMR (100MHz, CDCl3)δ：
179.1,145.0,140.1,140.0,130.6,129.3,129.0 (2), 128.7,126.5,125.5,123.2,119.2,
115.3,110.7,68.3；HRMS m/z(ESI)calcd for C20H17N2O([M+H]+) 301.1335, found
301.1337。
14 compound of embodimentSynthesis
To volume be 20mL Schlenk reaction bulbs in add 0.3mmol 6- methyl -3- phenyl -2- indolones,
The morpholine of 0.6mmol, the I of 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, air
Reaction is stirred under atmospheric condition, reaction process is monitored through TLC or GC, the reaction was complete to raw material when small (4), after the completion of reaction
Reaction solution is concentrated under reduced pressure, and by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
White solid (91%yield)；1H NMR (400MHz, CDCl3)δ：9.10 (s, 1H), 7.58 (d, J=7.2Hz,
2H), 7.35-7.28 (m, 3H), 7.09 (s, 1H), 7.03 (d, J=8.0Hz, 1H), 6.81 (d, J=8.0Hz, 1H), 3.71
(t, J=7.6Hz, 4H), 2.65 (t, J=7.6Hz, 4H), 2.31 (s, 3H)；13C NMR (100MHz, CDCl3)δ：178.3
138.3 (2), 132.2,129.3,129.2,128.6,128.0,127.7,126.8,110.2,74.7,67.5,47.6,21.3；
HRMS m/z(ESI)calcd for C19H21N2O2([M+H]+) 309.1598, found 309.1596.
15 compound of embodimentSynthesis
To volume be 20mL Schlenk reaction bulbs in add 0.3mmol the chloro- 3- phenyl -2- indolones of 6-,
The morpholine of 0.6mmol, the I of 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, air
Reaction is stirred under atmospheric condition, reaction process is monitored through TLC or GC, the reaction was complete to raw material when small (4), after the completion of reaction
Reaction solution is concentrated under reduced pressure, and by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
White solid (63%yield)；1H NMR (400MHz, CDCl3)δ：8.74 (s, 1H), 7.56 (d, J=6.8Hz,
2H), 7.38-7.30 (m, 4H), 7.22 (d, J=8.0Hz, 1H), 6.85 (d, J=8.0Hz, 1H), 3.72 (t, J=7.6Hz,
4H), 2.65 (t, J=8.0Hz, 4H)；13C NMR (100MHz, CDCl3)δ：177.7,139.1,137.4,131.1,129.0,
128.9,128.5,128.3,127.5,126.4,111.3,74.8,67.4,47.6；HRMS m/z(ESI)calcd for
C18H18ClN2O2([M+H]+) 329.1051, found 329.1053.
16 compound of embodimentSynthesis
Add into the Schlenk reaction bulbs that volume is 20mL the 3- methyl -2- indolones of 0.3mmol, 0.6mmol
The I of quinoline, 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, under the conditions of air atmosphere
Stirring reaction, reaction process is monitored through TLC or GC, and the reaction was complete to raw material when small (4), and the reaction solution after the completion of reaction is depressurized
Concentration, by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
White solid (92%yield)；1H NMR (400MHz, CDCl3)δ：8.71 (s, 1H), 7.30 (d, J=7.2Hz,
1H), 7.23 (t, J=8.0Hz, 1H), 7.06 (t, J=7.6Hz, 1H), 6.90 (d, J=7.6Hz, 1H), 3.69 (t, J=
4.4Hz, 4H), 2.70 (t, J=4.8Hz, 4H), 1.54 (s, 3H)；13C NMR (100MHz, CDCl3)δ：180.3 140.3,
131.7,128.7,124.2,122.8,110.1,67.4,66.6,47.1,21.5；HRMS m/z(ESI)calcd for
C13H17N2O2([M+H]+) 233.1285, found 233.1287.
17 compound of embodimentSynthesis
To volume be 20mL Schlenk reaction bulbs in add 0.3mmol N- methyl -3- phenyl -2- indolones,
The morpholine of 0.6mmol, the I of 0.06mmol2, 0.6mmol TBHP and dichloroethanes (2mL), reaction bulb is placed in 60 DEG C, air
Reaction is stirred under atmospheric condition, reaction process is monitored through TLC or GC, the reaction was complete to raw material when small (4), after the completion of reaction
Reaction solution is concentrated under reduced pressure, and by residue, through column chromatography for separation, (eluting solvent is：Ethyl acetate/normal hexane) obtain target product.
White solid (49%yield)；1H NMR (400MHz, CDCl3)δ：7.56 (d, J=7.6Hz, 2H), 7.36-
7.30 (m, 5H), 7.09 (t, J=7.6Hz, 1H), 6.87 (d, J=8.0Hz, 1H), 3.70 (t, J=6.8Hz, 4H), 3.23
(s, 3H), 2.59 (t, J=8.0Hz, 4H)；13C NMR (100MHz, CDCl3)δ：177.4,143.5,138.3,129.0,
128.6,128.1,127.7,127.2,125.9,122.8,108.4,74.2,67.5,47.6,26.2；HRMS m/z(ESI)
calcd for C19H21N2O2([M+H]+) 309.1598, found 309.1594.
Claims (9)
1. a kind of preparation method of 3- amidos -2- indole ketone compounds, it is characterised in that this method is with 2- indole ketone chemical combination
Thing and amine are raw material, are prepared through the following steps：The 2- indolones shown in formula 1a are added into Schlenk reaction bulbs
Aminated compounds, catalyst, oxidant and organic solvent shown in derivative, formula 2a, 60 DEG C, air atmosphere are placed in by reaction bulb
Under the conditions of stirring reaction in oil bath, monitor reaction process through TLC or GC, the reaction was complete to raw material, post-treated to obtain Formulas I institute
The target product 3- amido -2- indole ketone compounds shown.Its reaction equation represents as follows：
The product 3- amido -2- indole ketone compounds that the raw material 2- indole ketone compounds and Formulas I that above-mentioned formula 1a is represented represent
In, R1Represent one or more substituents, each R on its phenyl ring connected1It is independently from each other hydrogen, C1-C6Alkyl, C1-C6
Alkoxy, C1-C6Acyl group, C1-C6Ester group, halogen, cyano group, nitro, C3-C6Cycloalkyl, C5-C14Aryl, C5-C14Heteroaryl ,-
NRaRb；Wherein, Ra, RbIt is independently from each other C1-C6Alkyl or hydrogen；The hetero atom of the heteroaryl is selected from O, S or N；
R2Represent hydrogen, C1-C6Alkyl, halogen, cyano group, C3-C6Cycloalkyl, C5-C14Aryl, C5-C14Heteroaryl；The heteroaryl
Hetero atom is selected from O, S or N；
R3Represent hydrogen, tertbutyloxycarbonyl (Boc), C1-C6Alkyl, C1-C6Acyl group, C3-C6Cycloalkyl, C5-C14Aryl, C5-C14Virtue
Base-C1-C6Alkyl, C5-C14Heteroaryl, the hetero atom of the heteroaryl are selected from O, S or N；
Wherein, above-mentioned each alkyl, alkoxy, cycloalkyl, aryl and heteroaryl can be further substituted with a substituent, described
Substituent is selected from halogen or C1-C6Alkyl；
In the compound that above-mentioned formula 2a is represented, various aminated compounds are represented.
2. according to the method described in claim 1, it is characterized in that, R1Represent that one or more substitute on its phenyl ring connected
Base, each R1It is independently from each other hydrogen, C1-C6Alkyl, halogen, C1-C6Alkoxy, nitro, C5-C14Aryl；
R2Represent hydrogen, C1-C6Alkyl, halogen, cyano group, C5-C14Aryl；
R3Represent hydrogen, tertbutyloxycarbonyl (Boc), C1-C6Alkyl, C1-C6Acyl group, phenyl, benzyl；Wherein described C1-C6Alkyl, C1-
C6Acyl group, phenyl, benzyl and/or C5-C14Aryl can be further substituted, and the substituent is selected from halogen or C1-C6Alkane
Base.
3. according to the method described in claim 1, it is characterized in that, the organic solvent may be selected from dichloroethanes, dichloromethane,
One or more in acetonitrile, tetrahydrofuran.
4. according to the method described in claim 3, it is characterized in that, the organic solvent is most preferably dichloroethanes.
5. according to the method described in claim 1, it is characterized in that, the air atmosphere pressure is 1atm.
6. according to the method described in claim 5, it is characterized in that it is nitrogen atmosphere to replace the air atmosphere.
7. according to the method described in claim 1, it is characterized in that, the addition of the aminated compounds of formula 2a is preferably formula 1a institutes
150~300mol% of the 2- indolone derivatives additions shown.
8. according to the method described in claim 7, it is characterized in that the addition of the aminated compounds of formula 2a is more preferably formula 1a
The 200mol% of shown 2- indolone derivatives additions.
9. according to the method described in claim 1, it is characterized in that, the post-processing operation is as follows：After the completion of reaction
Reaction solution is concentrated under reduced pressure, and is through column chromatography for separation, eluting solvent by residue：Ethyl acetate/n-hexane, obtains target product 3-
Amido -2- indole ketone compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711246143.0A CN108003086B (en) | 2017-11-15 | 2017-11-15 | Preparation method of 3-amino-2-indolone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711246143.0A CN108003086B (en) | 2017-11-15 | 2017-11-15 | Preparation method of 3-amino-2-indolone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108003086A true CN108003086A (en) | 2018-05-08 |
| CN108003086B CN108003086B (en) | 2020-08-14 |
Family
ID=62055735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711246143.0A Active CN108003086B (en) | 2017-11-15 | 2017-11-15 | Preparation method of 3-amino-2-indolone compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108003086B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658836A (en) * | 2018-05-15 | 2018-10-16 | 宁波大学 | A kind of preparation method of 3- substitutions -3- azido indole-2-ketone compounds |
| CN109776387A (en) * | 2019-03-14 | 2019-05-21 | 宁波大学 | The preparation method of 3- peroxy -2- indole ketone compound in a kind of water phase |
| CN110467558A (en) * | 2019-08-08 | 2019-11-19 | 山东省科学院新材料研究所 | A kind of nickel catalyzes and synthesizes the reaction method of 3- amido isoindolinone |
| CN110577529A (en) * | 2019-10-10 | 2019-12-17 | 常州工程职业技术学院 | Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101516366A (en) * | 2006-09-21 | 2009-08-26 | 霍夫曼-拉罗奇有限公司 | Oxindole derivatives as anticancer agents |
| CN101516877A (en) * | 2006-09-22 | 2009-08-26 | 诺瓦提斯公司 | Heterocyclic organic compounds |
| WO2016133217A1 (en) * | 2015-02-20 | 2016-08-25 | 国立大学法人名古屋大学 | Method for producing optically active oxindole compound and triazolium salt used therein as catalyst |
-
2017
- 2017-11-15 CN CN201711246143.0A patent/CN108003086B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101516366A (en) * | 2006-09-21 | 2009-08-26 | 霍夫曼-拉罗奇有限公司 | Oxindole derivatives as anticancer agents |
| CN101516877A (en) * | 2006-09-22 | 2009-08-26 | 诺瓦提斯公司 | Heterocyclic organic compounds |
| WO2016133217A1 (en) * | 2015-02-20 | 2016-08-25 | 国立大学法人名古屋大学 | Method for producing optically active oxindole compound and triazolium salt used therein as catalyst |
Non-Patent Citations (2)
| Title |
|---|
| LETIZIA PULEO，ET AL.: "Synthesis and pharmacological evaluation of indolinone derivatives as novel ghrelin receptor antagonists", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| MANJUNATH LAMANI，ET AL.: "NIS-Catalyzed Reactions: Amidation of Acetophenones and Oxidative Amination of Propiophenones", 《CHEM. EUR. J.》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658836A (en) * | 2018-05-15 | 2018-10-16 | 宁波大学 | A kind of preparation method of 3- substitutions -3- azido indole-2-ketone compounds |
| CN108658836B (en) * | 2018-05-15 | 2021-04-20 | 宁波大学 | Preparation method of 3-substituted-3-azidoindole-2-ketone compound |
| CN109776387A (en) * | 2019-03-14 | 2019-05-21 | 宁波大学 | The preparation method of 3- peroxy -2- indole ketone compound in a kind of water phase |
| CN109776387B (en) * | 2019-03-14 | 2022-04-05 | 宁波大学 | Preparation method of 3-peroxy-2-indolone compounds in aqueous phase |
| CN110467558A (en) * | 2019-08-08 | 2019-11-19 | 山东省科学院新材料研究所 | A kind of nickel catalyzes and synthesizes the reaction method of 3- amido isoindolinone |
| CN110467558B (en) * | 2019-08-08 | 2022-09-16 | 山东省科学院新材料研究所 | Reaction method for synthesizing 3-aminoisoindolinone under catalysis of nickel |
| CN110577529A (en) * | 2019-10-10 | 2019-12-17 | 常州工程职业技术学院 | Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108003086B (en) | 2020-08-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108003086A (en) | A kind of preparation method of 3- amidos -2- indole ketone compounds | |
| CN108409747B (en) | Synthetic method of 2-aminoquinoline dihydrofuran compound | |
| CN107141246B (en) | A kind of preparation method of Isatine derivatives | |
| CN111205279B (en) | Polysubstituted benzodihydrofuran heterocyclic compound and preparation method and application thereof | |
| CN109956894B (en) | Synthetic method of 3, 3' -disubstituted-2-indolone compound | |
| CN110590788A (en) | 2-acyl-9H-pyrrolo [1,2-a]Synthesis method of indole compound | |
| CN113754558B (en) | Method for synthesizing azobenzene through copper salt catalyzed C-N coupling reaction | |
| CN107778182B (en) | Method for synthesizing N-alkyl arylamine | |
| CN107686460B (en) | Preparation method of 3-substituted-3-hydroxy-2-indolone compound | |
| CN111100085B (en) | Preparation method of 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound | |
| CN112824412B (en) | Chiral 1 'H-spiro [ indoline-3, 4' -pyrano [2,3-c ] pyrazole ] -2-ketone compound | |
| CN108148046B (en) | Pyridyl bridged pyrazolyl indole derivative and its prepn and application | |
| CN108409630A (en) | The preparation method of 3- hydroxyl -2- indolone derivatives in a kind of water phase | |
| CN106854125B (en) | Method for preparing α -fluoro- β -ethynyl ketone compound containing two chiral centers | |
| CN113200980B (en) | Method for synthesizing indolizine compound under catalysis of silver | |
| WO2002004401A1 (en) | PROCESS FOR THE PREPARATION OF β-AMINO ALCOHOLS IN SYN CONFIGURATION | |
| CN108440378A (en) | A kind of preparation method for the 3- amino -2- indolone derivatives that hydrogen peroxide iodo- at room temperature promotes | |
| CN109400629A (en) | Indoles spirooxazine heterocycle compound and preparation method thereof | |
| CN113636968B (en) | Synthetic method of 3-acyl pyrrole compound | |
| CN108976186A (en) | A method of the four substituted furan class compound of preparation based on carbon-hydrogen link activation | |
| CN114539319B (en) | Chiral phosphine-dicyclophosphoramidite ligand and preparation method and application thereof | |
| CN107082749A (en) | A kind of preparation method of β nitrine alcohol compound | |
| CN108101758B (en) | Method for preparing chiral propargylated aliphatic six-membered carbocyclic ring compound | |
| CN115028569A (en) | Indoline-2-ketone-3-acetamide series compounds and preparation method thereof | |
| CN116462619A (en) | Preparation method of cyclopentenone derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |