CN110156800A - A kind of synthetic method of pyrans simultaneously [3,2-b] indole-2-ketone compound - Google Patents
A kind of synthetic method of pyrans simultaneously [3,2-b] indole-2-ketone compound Download PDFInfo
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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Abstract
This patent is related to organic chemistry filed; more particularly to one kind to replace acetylenic acid ester and N- acetylindole -3- ketone as raw material; in triazolium salt and alkali 1; in the presence of 11 carbon -7- alkene of 8- diazabicylo, using methylene chloride as solvent, reacted under room temperature, inert atmosphere protection; reaction solution is concentrated and is eluted; it collects eluent revolving and removes solvent, obtain pyrans simultaneously [3,2-b] indole-2-ketone compound.Synthetic method of the present invention has many advantages, such as that substrate applicable surface is relatively wide, reaction yield is high, easy to operate, reaction condition is mild, raw materials and reagents are simple and easy to get.
Description
Technical field
The invention belongs to organic chemical synthesis method, more particularly to a kind of pyrans simultaneously [3,2-b] indole-2-ketone chemical combination
The synthetic method of object.
Background technique
Simultaneously [3,2-b] indol-2-one structure is widely present in the drug molecule with multiple biological activities pyrans
(Antivir.Res.2006,69,9；J.Biol.Chem.2008,283,12819.), but the synthetic method of this kind of compound
It is very limited.Therefore, it is highly desirable to develop the method that one kind is general, convenient, efficiently prepares such compound.
Summary of the invention
Goal of the invention: the present invention provides a kind of easy to operate, reaction conditions mildly, wide substrate applicability, post-processing side
The method of simultaneously [3,2-b] indole-2-ketone compound of synthesizing pyran just.
Technical solution: a kind of synthetic method of pyrans described herein simultaneously [3,2-b] indole-2-ketone compound: with
Acetylenic acid ester and the N- acetylindole -3- ketone as shown in formula II shown in formula I is raw material, in carbone catalyst IV and such as formula V
Shown in alkali 1, it is anti-under inert atmosphere protection using methylene chloride as solvent under the effect of 11 carbon -7- alkene of 8- diazabicylo
Answer, reaction solution be concentrated after reaction, elute, collect eluent revolving remove solvent, obtain the pyrans as shown in formula III simultaneously [3,
2-b] indoles -3- ketone product；Reaction equation is as follows:
Wherein, R1Indicate aryl, heterocycle, alkyl or hydrogen atom, R2Indicate methyl, halogen atom or hydrogen atom.
The reaction refers to reacts 2-4h at room temperature, preferably reacts at 30 DEG C.
Preferably, the elution refers to using petroleum ether: ethyl acetate volume ratio is the mixed solvent of 10:1 as eluant, eluent
Column chromatographic elution.
Preferably, the compound I: compound ii: compound V: the mass ratio of the material of carbone catalyst IV is 2:1:2:
0.1。
The compound ii: the mass ratio of the material of methylene chloride is 1:385.
As the most preferred technical solution of the application are as follows: by acetylenic acid ester 0.3mmol shown in formula I, as shown in formula II
N- acetylindole -3- ketone 0.15mmol, alkali 0.3mmol, the carbone catalyst as shown in formula IV as shown in formula V
0.015mmol and 3mL methylene chloride is placed in 25mL two mouth flask, reacts 2-4h under room temperature inert atmosphere protection, will be reacted
Liquid concentration, through using petroleum ether: the mixed solvent that ethyl acetate volume ratio is 10:1 is removed as eluant, eluent column chromatographic elution, revolving
The isolated pyrans as shown in formula III of solvent simultaneously [3,2-b] indol-2-one product, structure is through nuclear magnetic resoance spectrum, high-resolution matter
Spectrum confirmation.
The utility model has the advantages that be compared to the prior art, a kind of pyrans of the application simultaneously [3,2-b] indole-2-ketone compound
Synthetic method have the advantage that (1) step is succinct, easy to operate；(2) it is carried out under the catalysis of the miscellaneous Cabbeen of N-, reacts item
Part is mild, and raw material is cheap and easy to get, can be completed in low temperature environment；(3) wide substrate applicability, convenient post-treatment, and yield is high；
(4) oxidation, reduction system are not had in reaction process, environmental-friendly, application prospect is wide.
Specific embodiment
The invention will now be further described with reference to specific embodiments, the advantages and features of the present invention will be with description and
It is apparent.But examples are merely exemplary for these, and it is not intended to limit the scope of the present invention in any way.Those skilled in the art
Member it should be understood that without departing from the spirit and scope of the invention can details to technical solution of the present invention and form into
Row modifications or substitutions, but these modifications and replacement are fallen within the protection scope of the present invention.
The reaction of embodiment 1:3- phenyl propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- phenyl propiolic acid 4- nitro phenyl ester 80.1mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 43mg, yield 95% after removing solvent.
Yellowish solid,mp:173-175℃.1H NMR(300MHz,CDCl3) δ 8.12 (d, J=8.5Hz, 1H),
7.88 (d, J=7.9Hz, 1H), 7.62-7.49 (m, 6H), 7.41 (t, J=7.6Hz, 1H), 6.30 (s, 1H), 1.85 (s,
3H).13C NMR(75MHz,CDCl3)δ170.6,161.2,149.5,147.5,138.0,136.3,130.4,129.7,
129.6,126.9,124.4,119.2,118.5,118.3,115.2,110.3,27.1.HRMS(ESI)calcd for
C19H14NO3(M+H)+:304.0974,found 304.0972.
The reaction of embodiment 2:3- (2- aminomethyl phenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (2- aminomethyl phenyl) propiolic acid 4- nitro phenyl ester 84.3mg (0.3mmol), N- acetylindole -3- ketone
26.3mg (0.15mmol), carbone catalyst 3.96mg (0.015mmol), 1,8- diazabicylo 11 as shown in formula IV
45 μ L (0.3mmol) and methylene chloride 3mL of carbon -7- alkene is placed in 25mL two-mouth bottle, anti-under the conditions of inert atmosphere protection, 30 DEG C
2h is answered, by reaction solution cooling concentration, through using petroleum ether: ethyl acetate is washed than the mixed solvent for 10:1 as eluant, eluent column chromatography
It is de-, the eluent part of all products detected is collected, revolving obtains product 43mg, yield 91% after removing solvent.
Yellowish solid,mp:167-169℃.1H NMR(300MHz,CDCl3) δ 8.04 (d, J=8.5Hz, 1H),
7.90 (d, J=7.8Hz, 1H), 7.56-7.50 (m, 1H), 7.46-7.29 (m, 5H), 6.21 (s, 1H), 2.29 (s, 3H),
1.87(s,3H).13C NMR(75MHz,CDCl3)δ169.9,161.0,149.7,147.0,137.5,135.9,134.9,
131.4,129.8,129.5,128.1,126.6,124.3,119.2,119.1,118.5,115.0,111.8,26.6,
19.9.HRMS(ESI)calcd for C20H16NO3(M+H)+:318.1130,found 318.1126.
The reaction of embodiment 3:3- (2- fluorophenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (2- fluorophenyl) propiolic acid 4- nitro phenyl ester 85.5mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 30mg, yield 63% after removing solvent.
Yellowish solid,mp:170-172℃.1H NMR(300MHz,CDCl3) δ 7.94 (d, J=8.7Hz, 2H),
7.63-7.48 (m, 3H), 7.44 (t, J=7.7Hz, 1H), 7.34 (t, J=7.5Hz, 1H), 7.20 (t, J=9.3Hz, 1H),
6.38(s,1H),2.34(s,3H).13C NMR(100MHz,CDCl3) δ 169.2,160.8,158.9 (d, J=247.9Hz),
(146.9,144.7,136.9,131.7 d, J=8.1Hz), 129.2,128.8 (d, J=2.8Hz), 125.05,125.02,
(124.9,124.1,119.5,118.7,115.8 d, J=21.2Hz), 114.5,112.9,26.5.HRMS (ESI) calcd
for C19H13FNO3(M+H)+:322.0879,found 322.0875.
The reaction of embodiment 4:3- (2- chlorphenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (2- chlorphenyl) propiolic acid 4- nitro phenyl ester 90.3mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 32mg, yield 65% after removing solvent.
Yellowish solid,mp:155-157℃.1H NMR(300MHz,CDCl3) δ 7.89 (dd, J=8.2,
2.9Hz,2H),7.58-7.36(m,6H),6.27(s,1H),2.29(s,3H).13C NMR(75MHz,CDCl3)δ168.9,
160.7,147.6,146.7,136.7,136.1,131.6,130.5,129.9,129.3,129.2,127.4,124.1,
119.5,118.7,114.5,113.2,26.4.HRMS(ESI)calcd for C19H13ClNO3(M+H)+:338.0584,
found 338.0582.
The reaction of embodiment 5:3- (2- bromophenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (2- bromophenyl) propiolic acid 4- nitro phenyl ester 103.5mg (0.3mmol), N- acetylindole -3- ketone
26.3mg (0.15mmol), carbone catalyst 3.96mg (0.015mmol), 1,8- diazabicylo 11 as shown in formula IV
45 μ L (0.3mmol) and methylene chloride 3mL of carbon -7- alkene is placed in 25mL two-mouth bottle, anti-under the conditions of inert atmosphere protection, 30 DEG C
2h is answered, by reaction solution cooling concentration, through using petroleum ether: ethyl acetate is washed than the mixed solvent for 10:1 as eluant, eluent column chromatography
It is de-, the eluent part of all products detected is collected, revolving obtains product 28mg, yield 50% after removing solvent.
Yellowish solid,mp:158-160℃.1H NMR(300MHz,CDCl3)δ7.92-7.87(m,2H),7.67
(d, J=8.0Hz, 1H), 7.59-7.29 (m, 5H), 6.26 (s, 1H), 2.29 (s, 3H)13C NMR(75MHz,CDCl3)δ
168.9,160.7,149.0,146.8,138.1,136.7,133.2,130.6,129.5,129.2,127.9,124.1,
121.1,119.5,118.8,118.6,114.6,113.2,26.5.HRMS(ESI)calcd for C19H13BrNO3(M+H)+:
382.0079,found 382.0081.
The reaction of embodiment 6:3- (3- aminomethyl phenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (3- aminomethyl phenyl) propiolic acid 4- nitro phenyl ester 84.3mg (0.3mmol), N- acetylindole -3- ketone
26.3mg (0.15mmol), carbone catalyst 3.96mg (0.015mmol), 1,8- diazabicylo 11 as shown in formula IV
45 μ L (0.3mmol) and methylene chloride 3mL of carbon -7- alkene is placed in 25mL two-mouth bottle, anti-under the conditions of inert atmosphere protection, 30 DEG C
2h is answered, by reaction solution cooling concentration, through using petroleum ether: ethyl acetate is washed than the mixed solvent for 10:1 as eluant, eluent column chromatography
It is de-, the eluent part of all products detected is collected, revolving obtains product 45mg, yield 96% after removing solvent.
Yellowish solid,mp:154-156℃.1H NMR(300MHz,CDCl3) δ 8.13 (d, J=8.5Hz, 1H),
7.88 (d, J=7.8Hz, 1H), 7.60-7.50 (m, 1H), 7.460-7.30 (m, 5H), 6.29 (s, 1H), 2.44 (s, 3H),
1.84(s,3H).13C NMR(75MHz,CDCl3)δ170.7,161.3,149.6,147.4,139.7,137.9,136.2,
131.2,129.6,127.5,124.3,124.1,119.1,118.5,118.4,115.2,110.1,27.1,21.5.HRMS
(ESI)calcd for C20H16NO3(M+H)+:318.1130,found 318.1129.
The reaction of embodiment 7:3- (3- fluorophenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (3- fluorophenyl) propiolic acid 4- nitro phenyl ester 85.5mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 42mg, yield 89% after removing solvent.
Yellowish solid,mp:183-185℃.1H NMR(300MHz,CDCl3) δ 8.06 (d, J=8.5Hz, 1H),
7.88 (d, J=7.8Hz, 1H), 7.62-7.47 (m, 2H), 7.42 (t, J=7.6Hz, 1H), 7.35 (d, J=7.7Hz, 1H),
7.31-7.19(m,2H),6.28(s,1H),2.06(s,3H).13C NMR(75MHz,CDCl3) δ 170.0,163.1 (d, J=
247.9Hz), 160.9,148.3 (d, J=2.2Hz), 147.7,138.5 (d, J=7.8Hz), 137.9,131.3 (d, J=
8.3Hz), 129.7,124.5,122.6 (d, J=3.1Hz), 119.3,118.8,118.1,117.2 (d, J=20.9Hz),
115.1,113.9 (d, J=22.8Hz), 110.8,27.0.HRMS (ESI) calcd for C19H13FNO3(M+H)+:
322.0879,found 322.0873.
The reaction of embodiment 8:3- (3- chlorphenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (3- chlorphenyl) propiolic acid 4- nitro phenyl ester 90.3mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 44mg, yield 88% after removing solvent.
Yellowish solid,mp:178-180℃.1H NMR(300MHz,CDCl3) δ 8.04 (d, J=8.5Hz, 1H),
7.90 (d, J=7.8Hz, 1H), 7.61-7.53 (m, 2H), 7.51-7.39 (m, 4H), 6.28 (s, 1H), 2.09 (s, 3H)13C
NMR(75MHz,CDCl3)δ169.9,160.9,148.3,147.8,138.2,137.8,135.6,130.8,130.3,129.7,
126.8,124.9,124.5,119.4,118.9,118.2,115.1,110.8,27.0.HRMS(ESI)calcd for
C19H13ClNO3(M+H)+:338.0584,found 338.0578.
The reaction of embodiment 9:3- (4- aminomethyl phenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (4- aminomethyl phenyl) propiolic acid 4- nitro phenyl ester 84.3mg (0.3mmol), N- acetylindole -3- ketone
26.3mg (0.15mmol), carbone catalyst 3.96mg (0.015mmol), 1,8- diazabicylo 11 as shown in formula IV
45 μ L (0.3mmol) and methylene chloride 3mL of carbon -7- alkene is placed in 25mL two-mouth bottle, anti-under the conditions of inert atmosphere protection, 30 DEG C
2h is answered, by reaction solution cooling concentration, through using petroleum ether: ethyl acetate is washed than the mixed solvent for 10:1 as eluant, eluent column chromatography
It is de-, the eluent part of all products detected is collected, revolving obtains product 44mg, yield 94% after removing solvent.
Yellowish solid,mp:203-205℃.1H NMR(300MHz,CDCl3) δ 8.14 (d, J=8.5Hz, 1H),
7.88 (d, J=7.8Hz, 1H), 7.58-7.51 (m, 1H), 7.47 (d, J=8.1Hz, 2H), 7.41 (t, J=7.5Hz, 1H),
7.34 (d, J=8.0Hz, 2H), 6.28 (s, 1H), 2.44 (s, 3H), 1.85 (s, 3H)13C NMR(75MHz,CDCl3)δ
170.9,161.4,149.5,147.5,140.9,138.0,133.4,130.4,129.6,126.9,124.4,119.1,
118.6,118.5,115.2,109.9,27.2,21.4.HRMS(ESI)calcd for C20H16NO3(M+H)+:318.1130,
found 318.1124.
The reaction of embodiment 10:3- (4- methoxyphenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (4- methoxyphenyl) propiolic acid 4- nitro phenyl ester 89.2mg (0.3mmol), N- acetylindole -3- ketone
26.3mg (0.15mmol), carbone catalyst 3.96mg (0.015mmol), 1,8- diazabicylo 11 as shown in formula IV
45 μ L (0.3mmol) and methylene chloride 3mL of carbon -7- alkene is placed in 25mL two-mouth bottle, anti-under the conditions of inert atmosphere protection, 30 DEG C
3h is answered, by reaction solution cooling concentration, through using petroleum ether: ethyl acetate is washed than the mixed solvent for 10:1 as eluant, eluent column chromatography
It is de-, the eluent part of all products detected is collected, revolving obtains product 27mg, yield 55% after removing solvent.
Yellowish solid,mp:192-194℃.1H NMR(400MHz,CDCl3) δ 8.14 (d, J=8.5Hz, 1H),
7.87 (d, J=7.8Hz, 1H), 7.56-7.51 (m, 3H), 7.40 (t, J=7.5Hz, 1H), 7.04 (d, J=8.5Hz, 2H),
6.25(s,1H),3.89(s,3H),1.87(s,3H).13C NMR(100MHz,CDCl3)δ171.0,161.4,161.3,
149.1,147.5,138.0,129.6,128.5,128.4,124.4,119.1,118.6,118.5,115.2,115.1,
109.3,55.5,27.3.HRMS(ESI)calcd for C20H16NO4(M+H)+:334.1079,found 334.1079.
The reaction of embodiment 11:3- (4- fluorophenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (4- fluorophenyl) propiolic acid 4- nitro phenyl ester 85.5mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 31mg, yield 65% after removing solvent.
Yellowish solid,mp:185-187℃.1H NMR(400MHz,CDCl3) δ 8.10 (d, J=8.5Hz, 1H),
7.89 (d, J=7.8Hz, 1H), 7.61-7.55 (m, 3H), 7.43 (t, J=7.5Hz, 1H), 7.29-7.23 (m, 2H), 6.27
(s,1H),2.01(s,3H).13C NMR(100MHz,CDCl3) δ 170.2,163.7 (d, J=250.0Hz), 161.0,148.5,
(147.6,137.9,132.5 d, J=3.5Hz), 129.6,128.8 (d, J=8.3Hz), 124.5,119.3,118.7,
118.3,116.8 (d, J=21.7Hz), 115.1,110.3,27.1.HRMS (ESI) calcd for C19H13FNO3(M+H)+:
322.0879,found 322.0878.
The reaction of embodiment 12:3- (4- chlorphenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (4- chlorphenyl) propiolic acid 4- nitro phenyl ester 90.3mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 31mg, yield 62% after removing solvent.
Yellowish solid,mp:213-215℃.1H NMR(300MHz,CDCl3) δ 8.07 (d, J=8.5Hz, 1H),
7.90 (d, J=7.8Hz, 1H), 7.60-7.49 (m, 5H), 7.43 (t, J=7.3Hz, 1H), 6.27 (s, 1H), 2.03 (s,
3H).13C NMR(75MHz,CDCl3)δ170.0,160.9,148.5,147.7,137.9,136.5,134.9,129.8,
129.6,128.1,124.5,119.3,118.8,118.2,115.1,110.5,27.1.HRMS(ESI)calcd for
C19H13ClNO3(M+H)+:338.0584,found 338.0580.
The reaction of embodiment 13:3- (4- bromophenyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (4- bromophenyl) propiolic acid 4- nitro phenyl ester 103.5mg (0.3mmol), N- acetylindole -3- ketone
26.3mg (0.15mmol), carbone catalyst 3.96mg (0.015mmol), 1,8- diazabicylo 11 as shown in formula IV
45 μ L (0.3mmol) and methylene chloride 3mL of carbon -7- alkene is placed in 25mL two-mouth bottle, anti-under the conditions of inert atmosphere protection, 30 DEG C
2h is answered, by reaction solution cooling concentration, through using petroleum ether: ethyl acetate is washed than the mixed solvent for 10:1 as eluant, eluent column chromatography
It is de-, the eluent part of all products detected is collected, revolving obtains product 51mg, yield 90% after removing solvent.
Yellowish solid,mp:233-235℃.1H NMR(300MHz,CDCl3) δ 8.06 (d, J=8.5Hz, 1H),
7.88 (d, J=7.8Hz, 1H), 7.67 (d, J=8.4Hz, 2H), 7.55 (t, J=7.3Hz, 1H), 7.39-7.45 (m, 3H),
6.26(s,1H),2.04(s,3H).13C NMR(75MHz,CDCl3)δ170.0,161.0,148.5,147.7,137.9,
135.3,132.8,129.7,128.3,124.7,124.5,119.4,118.8,118.1,115.1,110.5,27.2.HRMS
(ESI)calcd for C19H13BrNO3(M+H)+:382.0079,found 382.0068.
The reaction of embodiment 14:3- (1- naphthalene) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (1- naphthalene) propiolic acid 4- nitro phenyl ester 95.2mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 4h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 45mg, yield 85% after removing solvent.
Yellowish solid,mp:94-96℃.1H NMR(500MHz,CDCl3)δ8.02-7.98(m,1H),7.95
(d, J=8.4Hz, 3H), 7.77 (d, J=8.4Hz, 1H), 7.62-7.46 (m, 5H), 7.42 (t, J=7.5Hz, 1H), 6.44
(s,1H),1.70(s,3H).13C NMR(75MHz,CDCl3)δ169.5,161.0,148.7,137.3,134.1,133.6,
130.3,129.7,129.4,128.9,127.4,126.8,126.0,125.5,124.4,124.2,119.4,118.6,
114.8,112.7,26.5.HRMS(ESI)calcd for C23H16NO3(M+H)+:354.1130,found 354.1122.
The reaction of embodiment 15:3- (2- thienyl) propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- (2- thienyl) propiolic acid 4- nitro phenyl ester 81.9mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 3h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 26mg, yield 58% after removing solvent.
Yellowish solid,mp:216-218℃.1H NMR(300MHz,CDCl3) δ 8.15 (d, J=8.5Hz, 1H),
7.87 (d, J=7.9Hz, 1H), 7.60-7.53 (m, 2H), 7.47 (d, J=3.4Hz, 1H), 7.41 (t, J=7.6Hz, 1H),
7.24-7.17(m,1H),6.34(s,1H),2.02(s,3H).13C NMR(75MHz,CDCl3)δ171.1,161.0,147.9,
142.6,138.4,137.1,129.8,129.5,128.79,128.75,124.5,119.2,118.6,118.1,115.3,
109.1,27.0.HRMS(ESI)calcd for C17H12NO3S(M+H)+:310.0538,found 310.0529.
Embodiment 16: the reaction of butyl- 2- acetylenic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By butyl- 2- acetylenic acid 4- nitro phenyl ester 61.5mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 3h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 24mg, yield 68% after removing solvent.
Yellowish solid,mp:178-180℃.1H NMR(500MHz,CDCl3) δ 7.84 (d, J=7.7Hz, 1H),
7.73 (d, J=8.6Hz, 1H), 7.58-7.46 (m, 1H), 7.37 (t, J=7.5Hz, 1H), 6.11 (d, J=1.1Hz, 1H),
2.84 (s, 3H), 2.41 (d, J=1.1Hz, 3H)13C NMR(75MHz,CDCl3)δ169.5,161.2,149.9,146.6,
136.7,128.7,124.1,121.4,119.8,119.6,114.3,111.6,27.2,22.1.HRMS(ESI)calcd for
C14H12NO3(M+H)+:242.0817,found 242.0807.
Embodiment 17: the reaction of amyl- 2- acetylenic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By amyl- 2- acetylenic acid 4- nitro phenyl ester 65.7mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 3h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 27mg, yield 72% after removing solvent.
White solid,mp:125-128℃.1H NMR(300MHz,CDCl3) δ 7.83 (d, J=7.8Hz, 1H), 7.72
(d, J=8.5Hz, 1H), 7.56-7.45 (m, 1H), 7.36 (t, J=7.5Hz, 1H), 6.15 (s, 1H), 2.91-2.74 (m,
5H), 1.21 (t, J=7.4Hz, 3H)13C NMR(75MHz,CDCl3)δ169.7,161.5,155.1,146.5,136.8,
128.6,124.0,120.9,119.7,114.2,109.6,27.3,27.1,12.1.HRMS(ESI)calcd for C15H14NO3
(M+H)+:256.0974,found 256.0963.
Embodiment 18: the reaction of octyl- 2- acetylenic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By octyl- 2- acetylenic acid 4- nitro phenyl ester 78.3mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 3h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 38mg, yield 87% after removing solvent.
Yellowish solid,mp:82-85℃.1H NMR(300MHz,CDCl3) δ 7.81 (d, J=7.7Hz, 1H),
7.71 (d, J=8.6Hz, 1H), 7.55-7.45 (m, 1H), 7.35 (t, J=7.5Hz, 1H), 6.12 (s, 1H), 2.83 (s,
3H), 2.76 (t, J=7.5Hz, 2H), 1.63-1.49 (m, 2H), 1.36-1.27 (m, 4H), 0.87 (t, J=6.8Hz, 3H)
.13C NMR(75MHz,CDCl3)δ169.7,161.4,153.9,146.6,136.7,128.5,124.0,120.8,119.64,
119.63,114.1,110.3,34.4,31.4,27.5,27.0,22.3,13.8.HRMS(ESI)calcd for C18H20NO3(M
+H)+:298.1443,found 298.1440.
The reaction of embodiment 19:3- cyclopropyl propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By 3- cyclopropyl propiolic acid 4- nitro phenyl ester 69.3mg (0.3mmol), N- acetylindole -3- ketone 26.3mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 3h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 36mg, yield 92% after removing solvent.
Yellowish solid,mp:146-148℃.1H NMR(300MHz,CDCl3)δ7.87-7.80(m,2H),7.51
(t, J=7.8Hz, 1H), 7.36 (t, J=7.5Hz, 1H), 5.79 (s, 1H), 2.79 (s, 3H), 2.12-1.99 (m, 1H),
1.22-1.13(m,2H),0.95-0.86(m,2H).13C NMR(75MHz,CDCl3)δ170.2,161.7,155.5,146.3,
137.3,128.9,124.2,121.4,119.6,119.3,114.5,105.2,27.3,14.5,11.0.HRMS(ESI)calcd
for C16H14NO3(M+H)+:268.0974,found 268.0965.
Embodiment 20: the reaction of propiolic acid 4- nitro phenyl ester and N- acetylindole -3- ketone
By propiolic acid 4- nitro phenyl ester 57.3mg (0.3mmol), N- acetylindole -3- ketone 26.3mg (0.15mmol),
The carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo, 45 μ L
(0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, react 4h under the conditions of inert atmosphere protection, 30 DEG C, will be reacted
Liquid cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, collects detection than the mixed solvent for 10:1
The eluent part of all products arrived, revolving obtain product 25mg, yield 75% after removing solvent.
Yellowish solid,mp:204-206℃.1H NMR(500MHz,CDCl3) δ 8.57 (d, J=9.9Hz, 1H),
7.91-7.87 (m, 2H), 7.54 (t, J=7.9Hz, 1H), 7.41 (t, J=7.6Hz, 1H), 6.32 (d, J=9.9Hz, 1H),
2.84(s,3H).13C NMR(75MHz,CDCl3)δ169.3,161.0,145.9,137.0,135.5,128.8,124.4,
119.7,119.5,119.4,115.2,112.3,27.2.HRMS(ESI)calcd for C13H10NO3(M+H)+:228.0661,
found 228.0652.
The reaction of embodiment 21:3- phenyl propiolic acid 4- nitro phenyl ester and N- acetyl group -5- methyl indol -3- ketone
By 3- phenyl propiolic acid 4- nitro phenyl ester 80.1mg (0.3mmol), N- acetyl group -5- methyl indol -3- ketone
28.4mg (0.15mmol), carbone catalyst 3.96mg (0.015mmol), 1,8- diazabicylo 11 as shown in formula IV
45 μ L (0.3mmol) and methylene chloride 3mL of carbon -7- alkene is placed in 25mL two-mouth bottle, anti-under the conditions of inert atmosphere protection, 30 DEG C
2h is answered, by reaction solution cooling concentration, through using petroleum ether: ethyl acetate is washed than the mixed solvent for 10:1 as eluant, eluent column chromatography
It is de-, the eluent part of all products detected is collected, revolving obtains product 36mg, yield 76% after removing solvent.
Yellowish solid,mp:206-208℃.1H NMR(300MHz,CDCl3) δ 7.99 (d, J=8.6Hz, 1H),
7.65 (s, 1H), 7.60-7.48 (m, 5H), 7.35 (dd, J=8.6,1.0Hz, 1H), 6.27 (s, 1H), 2.49 (s, 3H),
1.85(s,3H).13C NMR(75MHz,CDCl3)δ170.5,161.3,149.6,147.5,136.42,136.40,134.3,
131.1,130.3,129.6,126.9,118.7,118.5,115.0,110.1,27.0,21.2.HRMS(ESI)calcd for
C20H16NO3(M+H)+:318.1130,found 318.1121.
The reaction of embodiment 22:3- phenyl propiolic acid 4- nitro phenyl ester and N- acetyl group -5- chloro-indole -3- ketone
By 3- phenyl propiolic acid 4- nitro phenyl ester 80.1mg (0.3mmol), N- acetyl group -5- chloro-indole -3- ketone 31.6mg
(0.15mmol), the carbone catalyst 3.96mg (0.015mmol) as shown in formula IV, 11 carbon -7- alkene of 1,8- diazabicylo
45 μ L (0.3mmol) and methylene chloride 3mL are placed in 25mL two-mouth bottle, and 2h is reacted under the conditions of inert atmosphere protection, 30 DEG C, will
Reaction solution cooling concentration, through using petroleum ether: ethyl acetate, as eluant, eluent column chromatographic elution, is collected than the mixed solvent for 10:1
The eluent part of all products detected, revolving obtain product 40mg, yield 80% after removing solvent.
Yellowish solid,mp:224-226℃.1H NMR(300MHz,CDCl3) δ 8.07 (d, J=9.0Hz, 1H),
7.80 (d, J=2.0Hz, 1H), 7.55 (s, 5H), 7.46 (dd, J=9.0,2.1Hz, 1H), 6.32 (s, 1H), 1.80 (s,
3H).13C NMR(75MHz,CDCl3)δ170.4,160.7,149.1,146.0,136.1,135.9,130.6,130.1,
129.8,129.6,126.9,119.4,119.2,118.5,116.5,111.2,27.1.HRMS(ESI)calcd for
C19H13ClNO3(M+H)+:338.0584,found 338.0579.
Claims (5)
1. a kind of synthetic method of pyrans simultaneously [3,2-b] indole-2-ketone compound, it is characterised in that: with alkynes shown in formula I
Acid esters and the N- acetylindole -3- ketone as shown in formula II are raw material, in carbone catalyst IV and the alkali 1,8- as shown in formula V
Under the effect of 11 carbon -7- alkene of diazabicylo, using methylene chloride as solvent, reacted under inert atmosphere protection, after reaction
Reaction solution is concentrated, is eluted, eluent revolving is collected and removes solvent, obtain simultaneously [3, the 2-b] indoles -3- ketone of the pyrans as shown in formula III
Product；Reaction equation is as follows:
Wherein, R1Indicate aryl, heterocycle, alkyl or hydrogen atom, R2Indicate methyl, halogen atom or hydrogen atom.
2. synthetic method according to claim 1, which is characterized in that the reaction refers to reacts 2-4h at room temperature.
3. synthetic method according to claim 1, which is characterized in that the elution refers to petroleum ether: ethyl acetate body
Product is than being the mixed solvent of 10:1 as eluant, eluent column chromatographic elution.
4. synthetic method according to claim 1, which is characterized in that the compound I: compound ii: compound V: card
The mass ratio of the material of guest's catalyst IV is 2:1:2:0.1.
5. synthetic method according to claim 1, which is characterized in that the compound ii: the substance of methylene chloride
Amount ratio be 1:385.
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| CN113735868A (en) * | 2021-10-19 | 2021-12-03 | 西北工业大学 | Synthesis method of pyrano [3,2-b ] indole-2-ketone compound |
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| CN113735868A (en) * | 2021-10-19 | 2021-12-03 | 西北工业大学 | Synthesis method of pyrano [3,2-b ] indole-2-ketone compound |
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