CN106565709A - Preparation method and application of copper-catalyzed tetrahydropyrroloquinoline derivative - Google Patents
Preparation method and application of copper-catalyzed tetrahydropyrroloquinoline derivative Download PDFInfo
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- CN106565709A CN106565709A CN201610991354.6A CN201610991354A CN106565709A CN 106565709 A CN106565709 A CN 106565709A CN 201610991354 A CN201610991354 A CN 201610991354A CN 106565709 A CN106565709 A CN 106565709A
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- nafoxidine
- quinoline
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention discloses a preparation method of a tetrahydropyrroloquinoline derivative. The preparation method comprises the following steps: cuprous chloride, aminoalkyne and alkyne are added in a reaction flask, a solvent DMF (dimethyl formamide) is added to the reaction flask, an obtained mixture is subjected to a reaction for 30 min at the temperature of 150 DEG C under microwave irradiation, and a target product is obtained. According to the method, the yield is high, the time is short, the cost is low, a used substrate is not limited by terminal alkyne, good applicability to terminal alkyne and non-terminal alkyne is realized, and the defect of gold catalysis for the reaction is overcome; cell viability tests indicate that part of compounds prepared with the method have inhibitory activity on tumor cell proliferation, so that the method has potential application value in antitumor drug discovery.
Description
Technical field
The invention belongs to the preparation side of organic synthesis field, specifically a kind of nafoxidine of copper catalysis and quinoline
Method and application.
Background technology
Nitrogen-containing heterocycle compound, especially nafoxidine and quinoline, are widely present in natural products and biology is living
In property molecule.There is intramolecular hydroamination reaction using golden catalytic amino alkynes and generate enamine intermediates, and further occur and alkynes
Coupling reaction, the intramolecular cyclization reaction of hydrocarbon it has been reported that but the reaction except used catalyst costly, and reaction time
Long outer, the substrate of reaction is necessary for end alkynes, greatly limit substrate spectrum, and reaction equation is as follows：
The content of the invention
In order to solve above-mentioned technical problem, the invention provides the system of a kind of nafoxidine of copper catalysis and quinoline
Preparation Method and application.
The preparation method of a kind of nafoxidine of copper catalysis and quinoline, comprises the steps：By stannous chloride with
Amino alkynes, alkynes are added in reaction bulb, are added thereto to solvent DMF, and under microwave irradiation, 150 DEG C of reactions obtain target for 30 minutes and produce
Thing.
Described nafoxidine is simultaneously shown in quinoline structure such as formula (I)；
Wherein：
R1For hydrogen, alkyl (preferably C1～C6Alkyl), alkoxyl (preferably methoxyl group, ethyoxyl), halogen or aryl
(preferably phenyl ring and substituted benzene ring)；
R2For hydrogen, alkyl (preferably C1～C6Alkyl) or aryl (preferably phenyl ring and substituted benzene ring)；
R3For alkyl (preferably C1～C6Alkyl) or aryl (preferably phenyl ring and substituted benzene ring).
Shown in described amino alkynes structure such as formula (II)：
Wherein：
R1For hydrogen, alkyl (preferably C1～C6Alkyl), alkoxyl (preferably methoxyl group, ethyoxyl), halogen or aryl
(preferably phenyl ring and substituted benzene ring)；
R2For hydrogen, alkyl (preferably C1～C6Alkyl) or aryl (preferably phenyl ring and substituted benzene ring).
Shown in described alkynes structure such as structural formula (III)：
Wherein：
R3For alkyl (preferably C1～C6Alkyl) or aryl (preferably phenyl ring and substituted benzene ring).
In the present invention, amino alkynes is reacted under copper catalysis system, and alkynyl receives under the activation of copper catalyst
The nucleophilic attack of amino, forms enamine intermediates, and enamine intermediates obtain propargylamine intermediate by alkynes nucleophilic attack, again finally
There is intramolecular cyclization reaction and obtain final nafoxidine and quinoline.
Preferably, described copper catalyst is stannous chloride, consumption is the 1-10% of described amino alkynes, the copper catalysis
Agent is to the good substrate applicability in the present invention, high catalytic efficiency.
Preferably, described solvent is at least one of methyl alcohol, ethanol, n-hexane, DCM, DCE, DMF.As entering one
The step preferably solvent is DMF.
Preferably, reaction temperature is 75-180 DEG C, the too high meeting of reaction temperature causes nafoxidine and quinoline point
Solution, reaction temperature is too low, can reduce reaction conversion ratio, and used as further preferred, reaction temperature is 150 DEG C.
In the present invention, the time of reaction can be monitored by TLC (thin-layer chromatography chromatogram), be stirred at said temperatures
15-35 minutes react can be occurred completely.
For the compound that the method is obtained carries out biological activity test, find that there is certain suppression growth of tumour cell
Effect, the compound that brand new can be provided for the research and development of antineoplastic.
In order to improve reaction yield, it is possible to use super dry solvent is reacted in argon atmosphere, and useful molecules are sieved
As deicer, reaction is set preferably to carry out.
Method of the present invention high income, the time is fast, and low cost, substrate used is not limited to terminal alkyne, to end alkynes and
Non-end alkynes is respectively provided with good applicability, solves the defect that gold is catalyzed the reaction, and method according to the present invention is available
Replace analog derivative in diversified R2 is prepared, therefore with obvious advantage.Part of compounds Jing cell prepared by the method
Active testing, with tumor cell proliferation inhibition activity, shows that the method has potential application in antineoplastic discovery
Value.
Description of the drawings
Fig. 1 is product obtained in embodiment 21HNMR spectrograms.
Fig. 2 is product obtained in embodiment 213CNMR spectrograms.
Fig. 3 is product obtained in embodiment 31HNMR spectrograms.
Fig. 4 is product obtained in embodiment 313CNMR spectrograms.
Fig. 5 is product obtained in embodiment 41HNMR spectrograms.
Fig. 6 is product obtained in embodiment 413CNMR spectrograms.
Fig. 7 is the compound thing I-6 of variable concentrations to pancreatic cancer cell Capan-2 apoptosis and the impact result figure in cycle.
Specific embodiment
It is prepared by the amino acetylene compound of embodiment 1
3- butyne-1-ols (5.0g, 72mmol), imidazoles (6.8g, 100mmol) are added in single port bottle.Add dichloromethane
Alkane dissolves.Tert-butyl chloro-silicane (12.9g, 86mmol) is added under condition of ice bath, is stirred 30 minutes under room temperature, thin layer
After analysis chromatogram inspection reaction completely, dichloromethane is extracted, washing, is dried.Column chromatography (petrol ether/ethyl acetate=50:1)
13.2g colourless oil liquids.
The alkynol (15mmol) for weighing step gained TBS (tert-butyldimethyl silyl) protection adds anhydrous three neck to react
Bottle, adds anhydrous tetrahydro furan (20mL), reaction to be put in -78 DEG C of environment and stir under argon gas protective condition, slowly add thereto
Enter n-BuLi (2.5M, 8mL).Stir 1 hour under -78 DEG C of environment, add iodomethane (45mmol), room temperature reaction is overnight.
Add saturated ammonium chloride that reaction is quenched, EA is extracted, washing is dried.It is concentrated to give colorless oil.The grease is dissolved in anhydrous
THF, tetrabutyl ammonium fluoride (7.5mmol) is added in reaction system, is stirred 0.5 hour, and the inspection of thin-layer chromatography chromatogram has been reacted
Entirely, ethyl acetate is extracted, washing, is dried.Column chromatography (petrol ether/ethyl acetate=3:1) colourless oil liquid is obtained.
3- pentyne-1-alcohols (15.8mmol, 1.33g), triethylamine (19.0mmol, 2.7mL), 4- bis- are weighed in single port bottle
Methylamino pyridine (0.32mmol, 32mg).50mL dichloromethane is added in bottle, is stirred under condition of ice bath, it is right to add in three times
Toluene sulfochloride (16.6mmol, 3.16g).Add to put and stir 15 hours at room temperature.TLC detection reactions are finished, and add 30mL
10 minutes are stirred vigorously under NaOH saturated aqueous solution, room temperature.Dichloromethane is extracted, washing, is dried.Column chromatography (petroleum ether/
Ethyl acetate=10:1) 3.46g colourless oil liquids are obtained.
Aniline (or substituted aniline 3mmol, 1.5eq), sulphonic acid ester obtained in previous step are weighed in stand up reaction bottle
(2mmol, 448mg, 1.0eq), KI (0.2mmol, 33mg, 0.1eq).Add DMF (4mL) dissolvings.Add potassium carbonate
(6mmol, 818mg, 3eq).90 DEG C of heating stirrings, until thin-layer chromatography chromatogram detection sulphonic acid ester is consumed completely.Reaction is cooled to
Room temperature, the saturated aqueous solution for adding ammonium chloride is quenched reaction.Ethyl acetate is extracted three times, is washed five times, column chromatography (petroleum ether/
Ethyl acetate=30:1) colourless or pale yellow oily liquid is obtained.
Embodiment 2
Stannous chloride (2mg, 0.02mmol) is added under nitrogen atmosphere to a microwave tube equipped with magneton, then with note
Emitter adds 5mL dry DMFs, finally, addition amino alkynes (31.8mg, 0.2mmol) under nitrogen atmosphere, phenylacetylene (61.2mg,
0.6mmol) under microwave irradiation, 150 DEG C are reacted 30 minutes, after TLC detection reactions completely, add ethyl acetate, water stratification, acetic acid
Ethyl ester is washed 3 times, is washed 5 times, merges organic layer, anhydrous sodium sulfate drying.Cross post (eluant, eluent：Petrol ether/ethyl acetate=50/
1) yellow solid 47mg is obtained.Products therefrom1HNMR spectrograms,13CNMR spectrograms, referring to Fig. 1, Fig. 2.
Product physical property and spectral data are as follows：Yellow solid；1H NMR(500MHz,CDCl3)δ7.50–7.33(m,
5H), 7.16 (t, J=7.5Hz, 1H), 6.97 (d, J=7.5Hz, 1H), 6.57 (t, J=7.5Hz, 1H), 6.52 (d, J=
7.5Hz,1H),5.67(s,1H),3.59–3.42(m,2H),2.20–2.05(m,3H),2.02-1.92(m,1H),1.18(s,
3H).13C NMR(125MHz,CDCl3)δ143.42,140.23,135.96,129.27,128.90,128.13,127.78,
127.23,126.32,122.03,115.42,111.74,61.06,45.36,38.23,23.54,20.54。
Embodiment 3
Stannous chloride (2mg, 0.02mmol) is added under nitrogen atmosphere to a microwave tube equipped with magneton, then with note
Emitter adds 5mL dry DMFs, finally, addition amino alkynes (38.6mg, 0.2mmol) under nitrogen atmosphere, phenylacetylene (61.2mg,
0.6mmol) under microwave irradiation, 150 DEG C are reacted 30 minutes, after TLC (thin-layer chromatography chromatogram) detection reactions completely, add acetic acid second
Ester, water stratification, ethyl acetate is washed 3 times, is washed 5 times, merges organic layer, anhydrous sodium sulfate drying.Cross post (eluant, eluent：Petroleum ether/
Ethyl acetate=50/1) obtain yellow solid 42mg.Products therefrom1HNMR spectrograms,13CNMR spectrograms, referring to Fig. 3, Fig. 4.
Product physical property and spectral data are as follows：Yellow solid；1H NMR(500MHz,CDCl3)δ7.44–7.37(m,
3H), 7.35-7.31 (m, 2H), 7.07 (dd, J=8.5,2.5Hz, 1H), 6.90 (d, J=2.5Hz, 1H), 6.41 (d, J=
8.5Hz,1H),5.69(s,1H),3.53–3.46(m,1H),3.46–3.39(m,1H),2.15–2.05(m,3H),2.00-
1.96(m,1H),1.16(s,3H).13C NMR(126MHz,CDCl3)δ141.93,139.45,135.18,129.09,
128.80,128.38,128.29,127.48,125.83,123.40,120.34,112.76,64.13,61.19,45.53,
38.11,23.59,20.46.
Embodiment 4
Stannous chloride (2mg, 0.02mmol) is added under nitrogen atmosphere to a microwave tube equipped with magneton, then with note
Emitter adds 5mL dry DMFs, finally, addition amino alkynes (37.8mg, 0.2mmol) under nitrogen atmosphere, phenylacetylene (79.2mg,
0.6mmol) under microwave irradiation, 150 DEG C are reacted 30 minutes, after TLC detection reactions completely, add ethyl acetate, water stratification, acetic acid
Ethyl ester is washed 3 times, is washed 5 times, merges organic layer, anhydrous sodium sulfate drying.Cross post (eluant, eluent：Petrol ether/ethyl acetate=50/
1) yellow solid 52mg is obtained.Products therefrom1HNMR spectrograms,13CNMR spectrograms, referring to Fig. 5, Fig. 6.
Product physical property and spectral data are as follows：Yellow solid；1HNMR(500MHz,CDCl3) δ 7.30 (d, J=
8.5Hz, 2H), 6.94 (d, J=8.5Hz, 2H), 6.77 (dd, J=8.5,3.0Hz, 1H), 6.64 (s, 1H), 6.48 (s, 1H),
5.71(s,1H),3.87(s,3H),3.69(s,3H),3.44(s,2H),2.15–2.02(m,3H),2.01–1.92(m,1H),
1.11(s,3H).13C NMR(126MHz,CDCl3)δ158.96,150.80,138.31,135.25,132.40,130.24,
128.89,123.58,114.16,113.59,112.87,112.77,60.85,55.94,55.30,45.84,38.09,
22.58,20.76.
Cell growth inhibition assay is tested with the cell cycle：
Cell growth inhibition assay principle：SRB is a kind of pink anionic dye, soluble in water, in acid condition
CanSpecificityGround and intracellular compositionProtein'sBasic amino acidWith reference to；Produce under 540nm wavelengthAbsworption peak, light absorption value with
The linear positive correlation of cell concentration, therefore can be used as the quantitative determination of cell number.
Cell growth inhibition assay step：
(1) cell line is adopted：Pancreatic cancer cell Capan-2.
(2) after by the cell dissociation of exponential phase, single cell suspension is blown and beaten into, is inoculated in 96 well culture plates；4x103Carefully
Born of the same parents/hole.The complete medium containing 10% serum is added per hole, 5%CO is placed on2Incubator in overnight incubation.
(3) after cell attachment, the test-compound for adding gradient concentration is further cultured for 3 days in normal oxygen incubator, to comment
The rejection ability of valency drug candidate cell proliferation.
(4) Drug inhibition ability of cell proliferation is determined using srb assay.
(5) ELIASA detects each hole OD value (Detection wavelengths：540nm)；Record result；Inhibiting rate is calculated by following equation：
Inhibiting rate (%)=(OD control-OD administrations)/OD controls × 100%.Obtain result as shown in table 1 below：
The increment inhibitory activity of the compounds on pancreatic cancer cell capan2 of this patent of table 1 synthesis
As a result show, the compounds on pancreatic cancer cell synthesized with methods described has inhibited proliferation, wherein chemical combination
Thing I-6 inhibiting rates at 100 μM are 68.2%.
Cell cycle experimental principle：PI, i.e. propidium iodide, can be combined with intracellular DNA and RNA.Due to the cell cycle
The DNA content of each phase is different, and G1/G0 phases of usual normal cell have a DNA content (2N) of diploid cell, and the G2/M phases
DNA content (4N) with tetraploid cell, and the DNA content of S phases is between Diploid and Tetraploid.Therefore, by stream
When formula cell art PI decoration methods are detected to intracellular DNA content, cell cycle each phase can be divided into G1/G0 phases, S
Phase and G2/M phases, and the percentage of each phase can be calculated.
Cell cycle experimental procedure：
(1) cell line is adopted：Pancreatic cancer cell Capan-2.
(2) after by the cell dissociation of exponential phase, single cell suspension is blown and beaten into, is inoculated in 6 well culture plates；2x105Carefully
Born of the same parents/hole.The complete medium containing 10% serum is added per hole, 5%CO is placed on2Incubator in overnight incubation.
(3) after cell attachment, the test-compound for adding gradient concentration is further cultured for 1 day in normal oxygen incubator.
(4) digested with pancreatin and collected after cell, wash 3 times using phosphate buffer and resuspended to 1ml cell suspensions.
(5) the μ l of PI solution 10 of per group of 10 μ g/ml of addition, lucifuge is incubated 30 minutes after mixing.
(6) shadow using the compound thing I-6 of flow cytomery variable concentrations to the pancreatic cancer cell Capan-2 cycles
Ring, obtain result as shown in Figure 7：I-6 can block Capan-2 cells in the G0/G1 phases.
The foregoing is only presently preferred embodiments of the present invention, not to limit the present invention, all spirit in the present invention and
Any modification, equivalent and improvement for being made within principle etc., are all contained within protection scope of the present invention.
Claims (9)
1. the preparation method of a kind of nafoxidine of copper catalysis and quinoline, it is characterised in that comprise the steps：In copper
In the presence of catalyst, first there is intramolecular hydroamination reaction in amino alkynes, then react with alkynes, after the completion of reaction, after
Process obtains described nafoxidine and quinoline,
Described nafoxidine is simultaneously shown in quinoline structure such as formula (I)；
Wherein：
R1For hydrogen, alkyl, alkoxyl, halogen or aryl；
R2For hydrogen, alkyl or aryl；
R3For alkyl or aryl,
Shown in described amino alkynes structure such as formula (II)：
Wherein：
R1For hydrogen, alkyl, alkoxyl, halogen or aryl；
R2For hydrogen, alkyl or aryl；
Shown in described alkynes structure such as structural formula (III)：
Wherein：
R3For alkyl or aryl.
2. the preparation method of nafoxidine according to claim 1 and quinoline, it is characterised in that described copper is urged
Agent is stannous chloride, and consumption is the 1-10% of the amino alkynes.
3. the preparation method of nafoxidine according to claim 1 and quinoline, it is characterised in that described R1For
Hydrogen, methyl, ethyl, methoxyl group, ethyoxyl, fluorine, chlorine, bromine or phenyl ring.
4. the preparation method of nafoxidine according to claim 1 and quinoline, it is characterised in that described R2For
Hydrogen, methyl, ethyl or propyl group.
5. the preparation method of nafoxidine according to claim 1 and quinoline, it is characterised in that described R2For benzene
Base, benzyl, phenethyl, amyl group or Phenoxymethyl.
6. the preparation method of nafoxidine according to claim 1 and quinoline, it is characterised in that described solvent
For at least one in methyl alcohol, ethanol, n-hexane, DCM, DCE, DMF.
7. the preparation method of nafoxidine according to claim 1 and quinoline, it is characterised in that described reaction
Temperature is 75-180 DEG C.
8. the preparation method of nafoxidine according to claim 1 and quinoline, it is characterised in that in microwave irradiation
Under, 150 DEG C of reactions obtain target product in 30 minutes.
9. the preparation method gained compound of nafoxidine as claimed in any of claims 1 to 8 in one of claims and quinoline
Purposes in antineoplastic is prepared.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107098902A (en) * | 2017-06-09 | 2017-08-29 | 江西省科学院应用化学研究所 | A kind of synthetic method of pyrrolo- [1,2 a] quinoline |
| CN107488090A (en) * | 2017-06-22 | 2017-12-19 | 东北师范大学 | A kind of efficient catalytic asymmetry preparation method of N cyclopropyl nitrone compound |
| CN109651367A (en) * | 2019-02-18 | 2019-04-19 | 安徽理工大学 | A method of preparing 1,4- dihydroquinoline and pyrrolo- [1,2-a] quinolines |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105859718A (en) * | 2016-04-25 | 2016-08-17 | 浙江大学 | Preparation method of copper-catalyzed nitrogen-containing polyheterocyclic compound |
-
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- 2016-11-10 CN CN201610991354.6A patent/CN106565709B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105859718A (en) * | 2016-04-25 | 2016-08-17 | 浙江大学 | Preparation method of copper-catalyzed nitrogen-containing polyheterocyclic compound |
Non-Patent Citations (2)
| Title |
|---|
| CAN-LIANG MA ET AL.: "Gold-catalyzed tandem synthesis of bioactive spiro-dipyrroloquinolines and its application in the one-step synthesis of incargranine B aglycone and seneciobipyrrolidine (I)", 《ORG. CHEM. FRONT.,》 * |
| XIN-YUAN LIU ET AL.: "A Highly Efficient and Selective AuI-Catalyzed Tandem Synthesis of Diversely Substituted Pyrrolo[1,2-a]quinolines in Aqueous Media", 《ANGEW. CHEM. INT. ED.》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107098902A (en) * | 2017-06-09 | 2017-08-29 | 江西省科学院应用化学研究所 | A kind of synthetic method of pyrrolo- [1,2 a] quinoline |
| CN107488090A (en) * | 2017-06-22 | 2017-12-19 | 东北师范大学 | A kind of efficient catalytic asymmetry preparation method of N cyclopropyl nitrone compound |
| CN107488090B (en) * | 2017-06-22 | 2020-06-02 | 东北师范大学 | Efficient catalytic asymmetric preparation method of N-cyclopropyl nitrone compound |
| CN109651367A (en) * | 2019-02-18 | 2019-04-19 | 安徽理工大学 | A method of preparing 1,4- dihydroquinoline and pyrrolo- [1,2-a] quinolines |
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