CN105481865A - Preparation method of pyrimidine [1,6-a] indole heterocyclic derivative - Google Patents
Preparation method of pyrimidine [1,6-a] indole heterocyclic derivative Download PDFInfo
- Publication number
- CN105481865A CN105481865A CN201510976493.7A CN201510976493A CN105481865A CN 105481865 A CN105481865 A CN 105481865A CN 201510976493 A CN201510976493 A CN 201510976493A CN 105481865 A CN105481865 A CN 105481865A
- Authority
- CN
- China
- Prior art keywords
- preparation
- reaction
- indoles
- methane amide
- kui linpyrimido
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of a pyrimidine [1,6-a] indole heterocyclic derivative. The method comprises the following steps: under the condition that a rhodium catalyst, an additive silver salt and an additive acid exist, enabling an N-formamide indole compound and an a-carbonyl diazo compound to perform a cascade reaction in an organic solvent, and after the reaction is ended, separating and purifying to obtain the pyrimidine [1,6-a] indole heterocyclic derivative. The preparation method is mild in reaction condition, anhydrous and anaerobic conditions are not needed, and the operation is simple and convenient; besides, the reaction materials are easily prepared, and the substrate application scope is wide. By-products in the reaction only include nitrogen and water, and an economical, practical, green and environment-friendly novel method is provided for synthesizing the pyrimidine [1,6-a] indole heterocyclic derivative.
Description
Technical field
The invention belongs to technical field of organic synthesis.More specifically, the preparation method of a kind of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives is related to.
Background technology
Nitrogen heterocyclic is extensively present among natural product, and has good pharmaceutical activity and biological activity, and in existing medicines structure, majority all contains various types of nitrogen heterocyclic skeleton.Pyrimidines is the material that in vital movement, a class is important, is extensively present in human body and other biological body, as the usual ingredients in genetic material nucleic acid just has containing 3 kinds of pyrimidine structures.In addition, indole derivatives has important application in medicinal design.Therefore, with the also ring structure of these two kinds of nitrogen-containing heterocycle compounds, namely in antimalarial, anti-inflammatory, antibacterial, anticancer and analgesia etc., all demonstrate excellent pharmacologically active with the compound of Kui Linpyrimido quinoline [1,6-a] indoles heterocycle structure unit, there is important researching value.As three kinds contain the pharmaceutical activity molecule of Kui Linpyrimido quinoline [1,6-a] indole unit, its structural formula is as follows:
But the synthetic method of Kui Linpyrimido quinoline [1,6-a] the indoles Hete rocyclic derivatives of report is fewer at present, and building-up process more complicated, difficulty is high, there are problems, as: (1) reaction raw materials is relatively rareer, needs could be obtained by the synthesis path of multistep; (2) reaction conditions is too harsh, and temperature of reaction is too high, and synthetic yield is low.
Summary of the invention
The technical problem to be solved in the present invention overcomes existing Kui Linpyrimido quinoline [1,6-a] defect of synthetic method of indoles Hete rocyclic derivatives and deficiency, a kind of easy, efficient Kui Linpyrimido quinoline [1 is provided, 6-a] synthetic method of indoles Hete rocyclic derivatives, this synthetic method mild condition, easy and simple to handle, and compare environmental protection, as long as byproduct of reaction nitrogen G&W.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
A kind of preparation method of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives, comprises the steps: under rhodium catalyst, additive silver salt and additive acid existent condition, N-methane amide benzazolyl compounds and
there is cascade reaction in-carbonyl diazonium compound, obtains Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives in organic solvent;
Wherein, the structural formula of described N-methane amide benzazolyl compounds such as formula shown in (I), described in
the structural formula of-carbonyl diazonium compound is such as formula shown in (II), and the structural formula of described Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives is such as formula shown in (III);
In formula, R
1for 3-CH
3, 4-CH
3, 5-CH
3, 5-Br, 5-COOMe, 5-OMe, 6-CH
3, one in 6-Cl or 7-OMe; R
2for a kind of in Bn, Ph or alkyl; R
3for Me, Ph, Cy, MeOCH
2-or PhCH
2cH
2-in one; R
4for COOEt, COCH
3or the one in Ts.
Described N-methane amide indoles formula A and
-carbonyl diazonium compound formula B can be prepared with reference to existing method, specifically can see Org.Lett.2015, and 17,1349 and J.Am.Chem.Soc.2013,135,12204.
Wherein, preferably, the condition of described reaction is reacted 20 ~ 30 hours at 90 ~ 100 DEG C.
More preferably, the condition of described reaction is reacted 24 hours at 100 DEG C.
Preferably, described N-methane amide benzazolyl compounds and
the mol ratio of-carbonyl diazonium compound is 1:1 ~ 3.
More preferably, described N-methane amide benzazolyl compounds and
the mol ratio of-carbonyl diazonium compound is 1:2, and reaction compares thoroughly.
Preferably, described rhodium catalyst is [Cp*RhCl
2]
2, this kind of rhodium catalyst is to the good substrate applicability in the present invention, and catalytic efficiency is high.
Preferably, described rhodium catalyst [Cp*RhCl
2]
2consumption be 1 ~ 5mol% of described N-methane amide benzazolyl compounds.
More preferably, described rhodium catalyst [Cp*RhCl
2]
2consumption be the 2.5mol% of described N-methane amide benzazolyl compounds.
Preferably, described additive silver salt is AgClO
4, AgBF
4, AgNTf
2, AgOAc or AgSbF
6in one.
More preferably, described additive silver salt is AgSbF
6, its productive rate is higher.
Preferably, the consumption of described additive silver salt is 5 ~ 20mol% of described N-methane amide benzazolyl compounds.
More preferably, the consumption of described additive silver salt is the 15mol% of described N-methane amide benzazolyl compounds.
Preferably, described additive acid is trimethylacetic acid (PivOH).
Preferably, the consumption of described trimethylacetic acid (PivOH) is 20 ~ 100mol% of described N-methane amide benzazolyl compounds.
More preferably, the consumption of described trimethylacetic acid (PivOH) is the 50mol% of described N-methane amide benzazolyl compounds.
Preferably, described organic solvent is the one in second eyeball, ethanol, tetrahydrofuran (THF), toluene or 1,2-ethylene dichloride.
More preferably, described organic solvent is 1,2-ethylene dichloride.
Still more preferably, after described reaction terminates, carry out separation and purification, obtain Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives.
Can preferred embodiment as one, described separation and purification adopts column chromatography to carry out separation and purification.
The preferred reaction formula of above-mentioned preparation method is as follows:
In addition, according to Kui Linpyrimido quinoline [1,6-a] the indoles Hete rocyclic derivatives that above-mentioned preparation method prepares, also within protection scope of the present invention.
As concrete preferred embodiment, the embodiment of the present invention lists five kinds of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives, i.e. the preparation method of compound 1 ~ 5, described compound 1 ~ 5 is also within protection scope of the present invention.
The structural formula of described compound 1 ~ 5 is as follows:
The present invention has following beneficial effect:
The synthetic method of Kui Linpyrimido quinoline provided by the present invention [1,6-a] indoles Hete rocyclic derivatives has following significant advantage:
(1) easy and simple to handle, step is simple, mild condition, preparation method are insensitive to water and air in reaction process, does not need anhydrous and oxygen-free condition;
(2) react raw materials used easy preparation, be easy to purifying, avoid due to the use of plurality of reagents in polystep reaction and the wasting of resources caused the purification process etc. of each step reaction intermediate and environmental pollution;
(3) substrate is applied widely, and reaction yield is high;
(4) only having nitrogen G&W as by product in reaction, is a kind of economical and practical and novel method of environmental protection.
Accompanying drawing explanation
Fig. 1 is the hydrogen spectrogram of compound 1.
Fig. 2 is the carbon spectrogram of compound 1.
Fig. 3 is the hydrogen spectrogram of compound 2.
Fig. 4 is the carbon spectrogram of compound 2.
Fig. 5 is the hydrogen spectrogram of compound 3.
Fig. 6 is the carbon spectrogram of compound 3.
Fig. 7 is the hydrogen spectrogram of compound 4.
Fig. 8 is the carbon spectrogram of compound 4.
Fig. 9 is the hydrogen spectrogram of compound 5.
Figure 10 is the carbon spectrogram of compound 5.
Embodiment
Further illustrate the present invention below in conjunction with Figure of description and specific embodiment, but embodiment does not limit in any form to the present invention.Unless stated otherwise, the present invention adopts reagent, method and apparatus are the art conventional reagent, method and apparatus.
Unless stated otherwise, following examples agents useful for same and material are commercial.
Embodiment 1
1, the synthetic method of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives, comprises the following steps:
(1) in 10ml reaction tubes, add 5-bromo indole (38.8mg successively, 0.2mmol), 1,1'-carbonyl dimidazoles (35.6mg, 0.22mmol), 4-dimethylaminopyridine (5mg) and acetonitrile (2mL), this mixed solution is at 80 DEG C of back flow reaction 6h.After question response liquid is cooled to room temperature, then add benzylamine (21.4mg, 0.2mmol), continue to be warming up to 80 DEG C of back flow reaction 8h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=4:1) by silicagel column and obtains N-formyl benzylamine (5-bromine) indoles 55mg;
(2) in 10ml reaction tubes, [Cp*RhCl is added successively
2]
2(1.6mg, 2.5mol%), AgSbF
6(5.1mg, 10mol%), N-formyl benzylamine (5-bromine) indoles (32.8.0mg, 0.1mmol), methyl aceto acetate diazonium (30.8mg, 0.2mmol), trimethylacetic acid (5.1mg, 50mol%) with acetonitrile (1ml), this mixed solution is at 100 DEG C of stirring reaction 24h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=5:1) by silicagel column and obtains corresponding Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives 23.7mg, and productive rate is 54%.
2, the structural characterization data of the present embodiment products obtained therefrom are as follows:
1HNMR(400MHz,CDCl
3)δ8.50(d,J＝8.8Hz,1H),7.78(s,1H),7.41(d,J＝8.8Hz,1H),7.34(t,J＝7.2Hz,2H),7.29(d,J＝7.0Hz,2H),7.21(d,J＝7.3Hz,2H),6.80(s,1H),5.39(s,2H),4.44(q,J＝6.9Hz,2H),2.57(s,3H),1.45(t,J＝7.1Hz,3H)。Hydrogen spectrogram is shown in Fig. 1.
13CNMR(101MHz,CDCl
3)δ165.57,148.08,143.79,136.26,132.75,132.36,131.69,129.07,127.74,126.04,125.60,122.38,117.77,117.63,104.47,99.08,61.48,47.74,17.43,14.33。Carbon spectrogram is shown in Fig. 2.
Can judge that the structure of products obtained therefrom is as follows according to above data:
Embodiment 2
1, the synthetic method of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives, comprises the following steps:
(1) in 10ml reaction tubes, add 5-methoxy-Indole (29.4mg successively, 0.2mmol), 1,1'-carbonyl dimidazoles (35.6mg, 0.22mmol), 4-dimethylaminopyridine (5mg) and acetonitrile (2mL), this mixed solution is at 80 DEG C of back flow reaction 6h.After question response liquid is cooled to room temperature, then add benzylamine (21.4mg, 0.2mmol), continue to be warming up to 80 DEG C of back flow reaction 8h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=3:1) by silicagel column and obtains N-formyl benzylamine (5-methoxyl group) indoles 46.5mg;
(2) in 10ml reaction tubes, [Cp*RhCl is added successively
2]
2(1.6mg, 2.5mol%), AgSbF
6(5.1mg, 10mol%), N-formyl benzylamine (5-methoxyl group) indoles (28.0mg, 0.1mmol), methyl aceto acetate diazonium (30.8mg, 0.2mmol), trimethylacetic acid (5.1mg, 50mol%) with acetonitrile (1ml), this mixed solution is at 100 DEG C of stirring reaction 24h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=3:1) by silicagel column and obtains corresponding Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives 36.6mg, and productive rate is 94%.
2, the structural characterization data of the present embodiment products obtained therefrom are as follows:
1HNMR(400MHz,CDCl
3)δ8.52(d,J＝9.0Hz,1H),7.32(t,J＝7.3Hz,2H),7.26(d,J＝7.6Hz,1H),7.20(d,J＝7.5Hz,2H),7.09(s,1H),6.95(d,J＝9.0Hz,1H),6.80(s,1H),5.38(s,2H),4.43(q,J＝7.1Hz,2H),3.88(s,3H),2.53(s,3H),1.45(t,J＝7.1Hz,3H)。Hydrogen spectrogram is shown in Fig. 3.
13CNMR(101MHz,CDCl
3)δ165.86,157.05,148.08,142.92,136.58,132.31,131.72,129.01,127.87,127.61,126.06,117.05,112.06,104.42,101.83,99.70,61.32,55.62,47.60,17.32,14.35。Carbon spectrogram is shown in Fig. 4.
Can judge that the structure of products obtained therefrom is as follows according to above data:
Embodiment 3
1, the synthetic method of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives, comprises the following steps:
(1) in 10ml reaction tubes, add 7-methoxy-Indole (29.4mg successively, 0.2mmol), 1,1'-carbonyl dimidazoles (35.6mg, 0.22mmol), 4-dimethylaminopyridine (5mg) and acetonitrile (2mL), this mixed solution is at 80 DEG C of back flow reaction 6h.After question response liquid is cooled to room temperature, then add benzylamine (21.4mg, 0.2mmol), continue to be warming up to 80 DEG C of back flow reaction 8h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=3:1) by silicagel column and obtains N-formyl benzylamine (7-methoxyl group) indoles 44.8mg;
(2) in 10ml reaction tubes, [Cp*RhCl is added successively
2]
2(1.6mg, 2.5mol%), AgSbF
6(5.1mg, 10mol%), N-formyl benzylamine (7-methoxyl group) indoles (28.0mg, 0.1mmol), methyl aceto acetate diazonium (30.8mg, 0.2mmol), trimethylacetic acid (5.1mg, 50mol%) with acetonitrile (1ml), this mixed solution is at 100 DEG C of stirring reaction 24h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=3:1) by silicagel column and obtains corresponding Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives 35.8mg, and productive rate is 92%.
2, the structural characterization data of the present embodiment products obtained therefrom are as follows:
1HNMR(400MHz,CDCl
3)δ7.30(t,J＝7.5Hz,3H),7.27–7.21(m,2H),7.18(d,J＝7.4Hz,2H),6.88(d,J＝8.5Hz,2H),5.39(s,2H),4.41(q,J＝7.1Hz,2H),4.00(s,3H),2.51(s,3H),1.43(t,J＝7.1Hz,3H)。Hydrogen spectrogram is shown in Fig. 5.
13CNMR(101MHz,CDCl
3)δ165.86,149.27,147.50,143.44,136.80,134.19,133.26,128.90,127.45,126.14,125.54,122.75,113.12,107.63,104.33,101.59,61.27,57.08,48.27,17.26,14.33。Carbon spectrogram is shown in Fig. 6.
Can judge that the structure of products obtained therefrom is as follows according to above data:
Embodiment 4
1, the synthetic method of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives, comprises the following steps:
(1) in 10ml reaction tubes, add indoles (23.4mg successively, 0.2mmol), 1,1'-carbonyl dimidazoles (35.6mg, 0.22mmol), 4-dimethylaminopyridine (5mg) and acetonitrile (2mL), this mixed solution is at 80 DEG C of back flow reaction 6h.After question response liquid is cooled to room temperature, then add 4-chloroaniline (25.4mg, 0.2mmol), continue to be warming up to 80 DEG C of back flow reaction 8h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=5:1) by silicagel column and obtains N-formyl (4-chlorine) aniline indoles 42.1mg;
(2) in 10ml reaction tubes, [Cp*RhCl is added successively
2]
2(1.6mg, 2.5mol%), AgSbF
6(5.1mg, 10mol%), N-formyl (4-chlorine) aniline indoles (27.0mg, 0.1mmol), methyl aceto acetate diazonium (30.8mg, 0.2mmol), trimethylacetic acid (5.1mg, 50mol%) with acetonitrile (1ml), this mixed solution is at 100 DEG C of stirring reaction 24h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=5:1) by silicagel column and obtains corresponding Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives 19.4mg, and productive rate is 51%.
2, the structural characterization data of the present embodiment products obtained therefrom are as follows:
1HNMR(400MHz,CDCl
3)δ8.52(d,J＝8.1Hz,1H),7.67(d,J＝7.6Hz,1H),7.53(d,J＝8.6Hz,2H),7.40–7.28(m,2H),7.28–7.21(m,2H),6.95(s,1H),4.46(q,J＝7.1Hz,2H),2.23(s,3H),1.48(t,J＝7.1Hz,3H)。Hydrogen spectrogram is shown in Fig. 7.
13CNMR(101MHz,CDCl
3)δ165.62,147.71,142.72,135.98,135.44,133.15,131.48,130.65,130.54,130.13,124.35,123.17,120.05,116.08,104.55,100.89,61.44,19.23,14.36。Carbon spectrogram is shown in Fig. 8.
Can judge that the structure of products obtained therefrom is as follows according to above data:
Embodiment 5
1, the synthetic method of Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives, comprises the following steps:
In 10ml reaction tubes, add [Cp*RhCl successively
2]
2(1.6mg, 2.5mol%), AgSbF
6(5.1mg, 10mol%), N-formyl benzylamine indoles (25.0mg, 0.1mmol), methyl ethyl diketone diazonium (25.2mg, 0.2mmol), trimethylacetic acid (5.1mg, 50mol%) and acetonitrile (1ml), this mixed solution is at 100 DEG C of stirring reaction 24h.After reaction terminates, be directly spin-dried for solvent acetonitrile, the crude product obtained is separated (sherwood oil: ethyl acetate=4:1) by silicagel column and obtains corresponding Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives 18.8mg, and productive rate is 57%.
2, the structural characterization data of the present embodiment products obtained therefrom are as follows:
1HNMR(400MHz,CDCl
3)δ8.67(d,J＝7.6Hz,1H),7.65(d,J＝7.2Hz,1H),7.36(dt,J＝21.2,7.1Hz,5H),7.28(d,J＝6.7Hz,2H),7.22(d,J＝7.4Hz,2H),6.52(s,1H),5.37(s,2H),2.63(s,3H),2.33(s,3H)。Hydrogen spectrogram is shown in Fig. 9.
13CNMR(101MHz,CDCl
3)δ199.85,148.42,137.72,136.57,133.05,131.56,130.42,129.05,127.68,126.13,124.34,123.03,119.78,116.34,114.07,98.17,47.44,31.53,16.87。Carbon spectrogram is shown in Figure 10.
As follows according to the structure of above inferred from input data products obtained therefrom:
Above-described embodiment is the present invention's preferably embodiment; but embodiments of the present invention are not restricted to the described embodiments; change, the modification done under other any does not deviate from spirit of the present invention and principle, substitute, combine, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (10)
1. a Kui Linpyrimido quinoline [1,6-a] preparation method of indoles Hete rocyclic derivatives, it is characterized in that, comprise the steps: under rhodium catalyst, additive silver salt and additive acid existent condition, there is cascade reaction in organic solvent in N-methane amide benzazolyl compounds and a-carbonyl diazonium compound, obtain Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives; Wherein, as shown in the formula (I), as shown in the formula (II), the structural formula of described Kui Linpyrimido quinoline [1,6-a] indoles Hete rocyclic derivatives as shown in the formula (III) for the structural formula of described a-carbonyl diazonium compound for the structural formula of described N-methane amide benzazolyl compounds;
In formula, R
1for 3-CH
3, 4-CH
3, 5-CH
3, 5-Br, 5-COOMe, 5-OMe, 6-CH
3, one in 6-Cl or 7-OMe; R
2for a kind of in Bn, Ph or alkyl; R
3for Me, Ph, Cy, MeOCH
2-or PhCH
2cH
2-in one; R
4for COOEt, COCH
3or the one in Ts.
2. preparation method according to claim 1, is characterized in that, the condition of described reaction is reacted 20 ~ 30 hours at 90 ~ 100 DEG C.
3. preparation method according to claim 1, is characterized in that, the condition of described reaction is reacted 24 hours at 100 DEG C.
4. preparation method according to claim 1, is characterized in that, the mol ratio of described N-methane amide benzazolyl compounds and a-carbonyl diazonium compound is 1:1 ~ 3.
5. preparation method according to claim 1, is characterized in that, described rhodium catalyst is [Cp*RhCl
2]
2, consumption is 1 ~ 5mol% of described N-methane amide benzazolyl compounds.
6. preparation method according to claim 1, is characterized in that, described additive silver salt is AgClO
4, AgBF
4, AgNTf
2, AgOAc or AgSbF
6in one, consumption is 5 ~ 20mol% of described N-methane amide benzazolyl compounds.
7. preparation method according to claim 1, is characterized in that, described additive acid is trimethylacetic acid, and consumption is 20 ~ 100mol% of described N-methane amide benzazolyl compounds.
8. preparation method according to claim 1, is characterized in that, described organic solvent is the one in second eyeball, ethanol, tetrahydrofuran (THF), toluene or 1,2-ethylene dichloride.
9. preparation method according to claim 1, is characterized in that, described organic solvent is 1,2-ethylene dichloride.
10. according to Kui Linpyrimido quinoline [1,6-a] the indoles Hete rocyclic derivatives that the arbitrary described preparation method of claim 1 ~ 9 prepares.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510976493.7A CN105481865B (en) | 2015-12-21 | 2015-12-21 | A kind of preparation method of pyrimido [1,6-a] indole Hete rocyclic derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510976493.7A CN105481865B (en) | 2015-12-21 | 2015-12-21 | A kind of preparation method of pyrimido [1,6-a] indole Hete rocyclic derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105481865A true CN105481865A (en) | 2016-04-13 |
| CN105481865B CN105481865B (en) | 2016-10-05 |
Family
ID=55669180
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510976493.7A Expired - Fee Related CN105481865B (en) | 2015-12-21 | 2015-12-21 | A kind of preparation method of pyrimido [1,6-a] indole Hete rocyclic derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105481865B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108727385A (en) * | 2018-07-14 | 2018-11-02 | 青岛科技大学 | A kind of preparation method of polysubstituted dihydro-pyrimidin diindyl ketone derivatives |
| CN109232585A (en) * | 2018-11-29 | 2019-01-18 | 青岛科技大学 | A kind of preparation method of polysubstituted pyrimidine and two indolone derivatives |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103755708A (en) * | 2013-12-31 | 2014-04-30 | 浙江大学 | Preparation method of indole or pyrrolopyrimidine derivative |
-
2015
- 2015-12-21 CN CN201510976493.7A patent/CN105481865B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103755708A (en) * | 2013-12-31 | 2014-04-30 | 浙江大学 | Preparation method of indole or pyrrolopyrimidine derivative |
Non-Patent Citations (1)
| Title |
|---|
| ZHANG, YAN等: "Rh(III)-Catalyzed C-H Activation/Cyclization of Indoles and Pyrroles: Divergent Synthesis of Heterocycles", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108727385A (en) * | 2018-07-14 | 2018-11-02 | 青岛科技大学 | A kind of preparation method of polysubstituted dihydro-pyrimidin diindyl ketone derivatives |
| CN108727385B (en) * | 2018-07-14 | 2020-09-08 | 青岛科技大学 | Preparation method of polysubstituted dihydropyrimido indolone derivative |
| CN109232585A (en) * | 2018-11-29 | 2019-01-18 | 青岛科技大学 | A kind of preparation method of polysubstituted pyrimidine and two indolone derivatives |
| CN109232585B (en) * | 2018-11-29 | 2021-01-26 | 青岛科技大学 | Preparation method of polysubstituted pyrimido-diindolone derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105481865B (en) | 2016-10-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107365275B (en) | High purity celecoxib | |
| Wang et al. | PPh3/I2/HCOOH: An efficient CO source for the synthesis of phthalimides | |
| CN105481865A (en) | Preparation method of pyrimidine [1,6-a] indole heterocyclic derivative | |
| CN105001169A (en) | Synthetic method for 3-aminoquinoxaline-2(1H)-ketone compound | |
| CN110878099B (en) | Preparation method of pyrrole [1,2, alpha ] indole alkaloid derivative | |
| CN105820174B (en) | A kind of preparation method of polysubstituted thiophene diindyl derivative | |
| CN115215796B (en) | Synthesis method of 3-acyl quinoline compound | |
| CN113912609B (en) | Preparation method of natural alkaloid tryptanthrin and derivatives thereof | |
| JP6548214B2 (en) | Catalyst having an aminosalicylaldimine ligand coordinated to metal and method for producing iodocyclic compound using the same | |
| CN108484509B (en) | One kind has Boc amino barbiturates-cyclohexadiene spiro-compound and its synthetic method | |
| CN113651788B (en) | 3-aminoalkylchromone compound and preparation method thereof | |
| CN106892826A (en) | A kind of preparation method and application of amine and imines N-methyl | |
| CN102127014B (en) | Azaphenanthrone compound and preparation method thereof | |
| CN114702425A (en) | Preparation method of (S) -2-amino- (S) -3- [ pyrrolidone-2' ] alanine derivative and intermediate | |
| CN108191736B (en) | 2, 3-disubstituted indole derivatives and preparation method thereof | |
| CN102718694B (en) | 3-cyan substituted indole compound and synthetic method thereof | |
| CN104478799A (en) | Preparation method of 1,4-diallyl isoquinoline | |
| CN105646288A (en) | Preparation method of carbamate derivatives | |
| CN105237492A (en) | Synthetic method for ezetimibe intermediate | |
| CN101747255B (en) | Isoindolinone compound containing eneyne structure and synthetic method thereof | |
| CN105503866A (en) | Compound acyl intermediate as well as synthetic method thereof and application thereof in preparing tadalafil | |
| CN101486696B (en) | Preparation of 2,5-dimethyl furan-3,4-dicarboxylic acid | |
| CN100593538C (en) | Method for preparing N-substituted acryloyl-2,5-pyrrole-dione compound | |
| CN109232282A (en) | A kind of synthetic method of 2- aminobenzophenone class compound | |
| CN102586356B (en) | Method for synthesizing quinoline heterocycle derivatives by way of enzyme catalysis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20161005 Termination date: 20171221 |