CN105732648A - Nitrogen heterocyclic ring compound of pyrrolofuran and synthetic method - Google Patents
Nitrogen heterocyclic ring compound of pyrrolofuran and synthetic method Download PDFInfo
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- CN105732648A CN105732648A CN201610074386.XA CN201610074386A CN105732648A CN 105732648 A CN105732648 A CN 105732648A CN 201610074386 A CN201610074386 A CN 201610074386A CN 105732648 A CN105732648 A CN 105732648A
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- ZLLKGEGADLJGMK-SLMZUGIISA-N CC(C)(C)Nc([n](C(C)(C)C)c1c2CO/C1=N\C(C)(C)C)c2-c(cccc1)c1[BrH]C Chemical compound CC(C)(C)Nc([n](C(C)(C)C)c1c2CO/C1=N\C(C)(C)C)c2-c(cccc1)c1[BrH]C ZLLKGEGADLJGMK-SLMZUGIISA-N 0.000 description 1
- OXBMFEKPASKAPE-XMHGGMMESA-N CC(C/C=C1/OCc2c1[n](C(C)(C)C)c(NC(C)(C)C)c2-c1ccc[s]1)C(C)(C)C Chemical compound CC(C/C=C1/OCc2c1[n](C(C)(C)C)c(NC(C)(C)C)c2-c1ccc[s]1)C(C)(C)C OXBMFEKPASKAPE-XMHGGMMESA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—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
- 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
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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Abstract
The invention belongs to the technical field of organic synthesis and discloses a nitrogen heterocyclic ring compound of pyrrolofuran and a synthetic method.The compound has a structural general formula shown as the formula (1), wherein R1 is H or alkyl or naphthyl or thienyl or phenyl or phenyl substituted by F, Cl, Br, I, alkyl, alkoxy, nitrile groups and ester groups; R2 is tertiary butyl or cyclohexyl or 1,1,3,3-tetramethyl-normal-butyl or adamantyl; R3 is H or alkyl.According to the synthetic method, alkynyl carbonate, a metal palladium catalyst, a ligand, alkali, water and a solvent are added into a reactor, isonitrile is added, the mixture is stirred for reacting for 8-16 hours at the temperature of 0-100 DEG C, the reaction product is subjected to extraction, separation and purification, and the nitrogen heterocyclic ring compound of pyrrolofuran is obtained.Through the synthetic method, reaction conditions are mild, operation is safe and simple, the raw materials are cheap and easy to get, the functional groups are good in applicability, the yield is excellent, and the synthetic method has good application prospects.(Please see the description for the formula (1).).
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to nitrogen-containing heterocycle compound and the synthetic method of a kind of pyrrolo-furan.
Background technology
Azaaromatics, intramolecular contains bigger conjugated system and strong cyclic voltammetry method, this special firm
Property condensed cyclic structure make nitrogen heterocyclic ring compounds show many unique performances and biological activity, photoelectric material, dyestuff, doctor
Medicine, Supramolecular Recognition etc. are multi-field has potential extensive application.What is more important heterocycle compound is prone to carry out structure and repaiies
Decorations, can become the most active research field with the more important functional molecular of synthesis ratio.
The nitrogen heterocyclic ring compounds of pyrrolo-furan, the imines hydrolysis on furan nucleus will become pyrrolo-five yuan after modifying a little
Cyclic lactone, can synthesize some antitumor, anticancer medicine (Amit Kumar Jana, Dipakranjan Mal. as reaction intermediate
Chem.Commun,2010,46,4411-4413；).Carbazole alkaloid (Joyeeta such as generating structure multiformity and bio-diversity
Roy,Dipakranjan Mal.Eur.J.Org.Chem.2014,1873–1881；Dipakranjan Mal,Joyeeta Roy,
Kumar Biradha.Org.Biomol.Chem.2014,12,8196-8203；D.Mal,B.Senapati,P.Pahari.
Tetrahedron Letters.2006,47,1071–1075).And how to provide a kind of condition gentleer, Atom economy is good,
Raw material is simple and easy to get, the construction method of the compound of the nitrogen heterocyclic ring class of easy to operate pyrrolo-furan, is the research of this area
The target that personnel make great efforts.
Summary of the invention
Based on above prior art, the primary and foremost purpose of the present invention is to provide the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan.
Another object of the present invention is to provide the synthetic method of the nitrogen-containing heterocycle compound of a kind of above-mentioned pyrrolo-furan.
The object of the invention is achieved through the following technical solutions:
The nitrogen-containing heterocycle compound of a kind of pyrrolo-furan, has a general structure shown in formula (1):
Formula (1),
In formula, R1For H, alkyl, naphthyl, thienyl, phenyl or F, Cl, Br, I, alkyl, alkoxyl, itrile group, ester
The substituted phenyl of base；R2For the tert-butyl group, cyclohexyl, 1,1,3,3-tetramethyl-normal-butyl or adamantyl；R3For H or alkyl.
The synthetic method of the nitrogen-containing heterocycle compound of above-mentioned pyrrolo-furan, comprises the following steps:
In reaction vessel, add alkynyl carbonic ester, metal palladium catalyst, part, alkali, water and solvent, add isonitrile,
0～100 DEG C of stirring reaction 8～16 hours, after question response terminates, pours reactant liquor into separatory funnel, by water and ethyl acetate
Mixed solvent extracts, and takes upper organic phase, and organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, and decompression is steamed
After ethyl acetate, obtaining crude product, crude by column chromatography purifies the nitrogen-containing heterocycle compound obtaining described pyrrolo-furan.
Above-mentioned reaction is shown below:
Preferably, described alkynyl carbonic ester is phenylpropyl alcohol alkynyl carbonic ester, 3-(2-aminomethyl phenyl)-2-propine carbonic ester, 3-(2-bromobenzene
Base)-2-propine carbonic ester, 3-(3-cyanophenyl)-2-propine carbonic ester, 3-(3-acetylphenyl)-2-propine carbonic ester, 3-(4-iodobenzene
Base)-2-propine carbonic ester, 3-(4 benzoic acid ethoxycarbonyl)-2-propine carbonic ester, 3-(2-naphthalene)-2-propine carbonic ester, 3-(2-thiophene)-2-
Propine carbonic ester, 3-hexin-2-methyl carbonate, 4-phenyl-3-crotonylene-methyl carbonate or phenylpropyl alcohol alkynyl carbonic ester.
Preferably, described isonitrile is tert-butyl isonitrile, 1,1,3,3-tetramethyl normal-butyl isonitrile or adamantyl isonitrile.
Preferably, described metal palladium catalyst is Palladous chloride., palladium iodide, palladium bromide, palladium, dichlorodiethyl nitrile palladium, trifluoro
Acid chloride or bi triphenyl phosphorus palladium chloride.
Preferably, described part is 1,10-phenanthrene quinoline, adjacent luxuriant and rich with fragrance quinoline, thricyclohexyl phosphorus, triphenyl phosphorus, tri-tert phosphorus, 2,2
'-bipyridyl, 4,4 '-bipyridyl or three (o-methyl-phenyl-) phosphorus.
Preferably, described alkali is triethylamine, pyridine, potassium carbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, tert-butyl alcohol lithium,
Potassium tert-butoxide, sodium tert-butoxide, sodium acetate, Sodium ethylate, cesium fluoride or cesium carbonate.
Preferably, described solvent is DMF, N,N-dimethylacetamide, toluene, Isosorbide-5-Nitrae-dioxane,
Dimethyl sulfoxide, 1,2-dichloroethanes, acetonitrile or oxolane.
Preferably, the addition of described metal palladium catalyst is (0.001～3) with the mol ratio of alkynyl carbonic ester: 1, with rubbing of water
Your ratio is (0.001～1): 1, is (0.001～4) with the mol ratio of alkali: 1, is (0.005～3) with the mol ratio of part: 1.
Preferably, the addition of described alkynyl carbonic ester and the mol ratio of isonitrile are (0.01～1): 1.
Preferably, described column chromatography purifies the mixed solvent using eluent to be petroleum ether and ethyl acetate, petroleum ether and acetic acid second
The volume ratio of ester is 1～(100:1).
Relative to prior art, the invention have the advantages that and beneficial effect:
A kind of nitrogen-containing heterocycle compound utilizing propargyl carbonic ester and isonitrile synthesis pyrrolo-furan of the present invention, reaction condition is gentle,
Operate safe and simple, cheaper starting materials is easy to get, functional group adaptability is good, good yields.Isonitrile can be real under the catalytic action of palladium
Existing polymolecular insertion, the nitrogenous heterocyclic skeleton that composite structure is relatively new, there is higher Atom economy.
Accompanying drawing explanation
Fig. 1 and Fig. 2 is hydrogen spectrogram and the carbon spectrogram of embodiment 1-11 products therefrom respectively；
Fig. 3 and Fig. 4 is hydrogen spectrogram and the carbon spectrogram of embodiment 12 products therefrom respectively；
Fig. 5 and Fig. 6 is hydrogen spectrogram and the carbon spectrogram of embodiment 13 products therefrom respectively；
Fig. 7 and Fig. 8 is hydrogen spectrogram and the carbon spectrogram of embodiment 14 products therefrom respectively；
Fig. 9 and Figure 10 is hydrogen spectrogram and the carbon spectrogram of embodiment 15 products therefrom respectively；
Figure 11 and Figure 12 is hydrogen spectrogram and the carbon spectrogram of embodiment 16 products therefrom respectively；
Figure 13 and Figure 14 is hydrogen spectrogram and the carbon spectrogram of embodiment 17 products therefrom respectively；
Figure 15 and Figure 16 is hydrogen spectrogram and the carbon spectrogram of embodiment 18 products therefrom respectively；
Figure 17 and Figure 18 is hydrogen spectrogram and the carbon spectrogram of embodiment 19 products therefrom respectively；
Figure 19 and Figure 20 is hydrogen spectrogram and the carbon spectrogram of embodiment 20 products therefrom respectively；
Figure 21 and Figure 22 is hydrogen spectrogram and the carbon spectrogram of embodiment 21 products therefrom respectively；
Figure 23 and Figure 24 is hydrogen spectrogram and the carbon spectrogram of embodiment 22 products therefrom respectively；
Figure 25 and Figure 26 is hydrogen spectrogram and the carbon spectrogram of embodiment 23 products therefrom respectively.
Detailed description of the invention
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited to this.
Embodiment 1
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, it is subsequently adding
Acetonitrile 2 milliliters, as solvent, stirs 2 hours at 90 DEG C.After terminating with TLC (thin layer chromatography) detection reaction, will be anti-
Answering liquid to pour separatory funnel into, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through anhydrous magnesium sulfate
Being dried and remove water, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude by column chromatography purifies and obtains target
Product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 48%.
Embodiment 2
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, it is subsequently adding
Dimethyl sulfoxide 2 milliliters, as solvent, stirs 2 hours at 90 DEG C.After terminating with TLC (thin layer chromatography) detection reaction,
Pouring reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through anhydrous sulfur
Acid magnesium is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography purifies and obtains
Target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 55%.
Embodiment 3
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, Palladous chloride. is added in the test tube of 25mL
0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, it is subsequently adding dimethyl sulfoxide 2
Milliliter, as solvent, stirs 2 hours at 90 DEG C.After terminating with TLC (thin layer chromatography) detection reaction, reactant liquor is fallen
Entering separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is dried through anhydrous magnesium sulfate and removes
Anhydrating, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude by column chromatography purifies and obtains target product,
Column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 38%.
Embodiment 4
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, palladium is added in the test tube of 25mL
0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, it is subsequently adding dimethyl sulfoxide 2
Milliliter, as solvent, stirs 2 hours at 90 DEG C.After terminating with TLC (thin layer chromatography) detection reaction, reactant liquor is fallen
Entering separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is dried through anhydrous magnesium sulfate and removes
Anhydrating, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude by column chromatography purifies and obtains target product,
Column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 42%.
Embodiment 5
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, 1,8-0.5 mM of diazabicylo 11 carbon-7-alkene,
One, water, is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, stirs 2 hours at 90 DEG C.With TLC (thin layer chromatography)
After detection reaction terminates, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase,
Organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, crude product warp
Column chromatography purify obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixing molten
Agent, productivity 38%.
Embodiment 6
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, potassium carbonate 0.5 mM, one, water, it is subsequently adding
Dimethyl sulfoxide 2 milliliters, as solvent, stirs 2 hours at 90 DEG C.After terminating with TLC (thin layer chromatography) detection reaction,
Pouring reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through anhydrous sulfur
Acid magnesium is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography purifies and obtains
Target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 27%.
Embodiment 7
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, pyridine 0.5 mM, one, water, it is subsequently adding two
Methyl sulfoxide 2 milliliters, as solvent, stirs 2 hours at 90 DEG C.After terminating with TLC (thin layer chromatography) detection reaction,
Pouring reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through anhydrous sulfur
Acid magnesium is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography purifies and obtains
Target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 22%.
Embodiment 8
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, 0.025 mM of thricyclohexyl phosphorus, cesium fluoride 0.5 mM, one, water, then add
Enter dimethyl sulfoxide 2 milliliters as solvent, stir 2 hours at 90 DEG C.Terminate with TLC (thin layer chromatography) detection reaction
After, to pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through nothing
Water magnesium sulfate is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography purifies
Obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity
43%.
Embodiment 9
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, 1,10-phenanthrene quinoline 0.025 mM, potassium carbonate 0.5 mM, one, water, then add
Enter dimethyl sulfoxide 2 milliliters as solvent, stir 2 hours at 90 DEG C.Terminate with TLC (thin layer chromatography) detection reaction
After, to pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through nothing
Water magnesium sulfate is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography purifies
Obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity
35%.
Embodiment 10
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, it is subsequently adding
Acetonitrile 2 milliliters, as solvent, stirs 2 hours at 50 DEG C.After terminating with TLC (thin layer chromatography) detection reaction, will be anti-
Answering liquid to pour separatory funnel into, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through anhydrous magnesium sulfate
Being dried and remove water, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude by column chromatography purifies and obtains target
Product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 50%.
Embodiment 11
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mM, bi triphenyl is added in the test tube of 25mL
Phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, it is subsequently adding
Dimethyl sulfoxide 2 milliliters, as solvent, stirs 12 hours at room temperature.After terminating with TLC (thin layer chromatography) detection reaction,
Pouring reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through anhydrous sulfur
Acid magnesium is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography purifies and obtains
Target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity 75%.
The hydrogen spectrogram of embodiment 1-11 products therefrom and carbon spectrogram are the most as depicted in figs. 1 and 2；Structural characterization data are as follows:
IR(KBr):3696,3082,2969,1688,1548,1362,1225,1019cm-1；
1H NMR(400MHz,CDCl3) δ 7.32 (d, J=4.0Hz, 4H), 7.17 (d, J=2.4Hz, 1H), 5.10 (s, 2H),
2.99(s,1H),1.86(s,9H),1.35(s,9H),0.86(s,9H)；
13C NMR(100MHz,CDCl3)δ149.78,140.20,137.05,133.47,128.40,128.37,125.51,124.70,
114.14,67.66,60.40,55.78,53.35,31.43,30.56,30.20；
mp:140-144℃；
HRMS(ESI)m/z:calcd for C24H36N3O,[M+H]+:382.2853,found 382.2860。
Infer that according to data above the structure of products therefrom is as follows:
Embodiment 12
3-(2-aminomethyl phenyl)-2-propine carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mmoles is added in the test tube of 25mL
You, bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, water one
Drip, be subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.Examine with TLC (thin layer chromatography)
After measured reaction terminates, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase,
Organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, crude product warp
Column chromatography purify obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixing molten
Agent, productivity 55%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in Figure 3 and Figure 4；Structural characterization data are as follows:
IR(KBr):3701,2966,1687,1556,1451,1362,1214,1026cm-1；
1H NMR (400MHz, CDCl3) δ 7.21 (d, J=4.4Hz, 1H), 7.14 (s, 3H), 4.94 (s, 2H), 2.62 (s, 1H),
2.28(s,3H),1.87(s,9H),1.35(s,9H),0.78(s,9H)；
13C NMR(100MHz,CDCl3)δ149.92,140.81,136.43,136.10,134.30,130.80,130.22,126.57,
125.60,123.96,113.30,68.02,60.32,54.97,53.34,31.60,30.60,30.03,20.07；
mp:130-133℃；
(ESI)m/z:calcd for C25H38N3O,[M+H]+:396.3009,found 396.3019。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 13
Addition 3-(2-bromophenyl)-2-propine carbonic ester 0.25 mM in the test tube of 25mL, tert-butyl isonitrile 0.80 mM,
Bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water,
It is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.Anti-with TLC (thin layer chromatography) detection
After should terminating, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic
Being dried removing water through anhydrous magnesium sulfate, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude product is through post layer
Analysis purification obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent,
Productivity 58%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in Figure 5 and Figure 6；Structural characterization data are as follows:
IR(KBr):3699,3107,2966,1686,1553,1362,1236,1020cm-1；
1H NMR (400MHz, CDCl3) δ 7.60 (d, J=8.0Hz, 1H), 7.27 (t, J=6.8Hz, 2H), 7.10 (t, J=6.4
Hz, 1H), 5.12 (d, J=13.2Hz, 1H), 4.95 (d, J=13.4Hz, 1H), 2.77 (s, 1H), 1.87 (s, 9H), 1.35 (s, 9H),
0.82(s,9H)；
13C NMR(100MHz,CDCl3)δ149.85,140.97,137.83,134.06,132.99,132.41,127.96,127.26,
124.22,113.40,68.14,60.58,55.05,53.36,31.59,30.58,30.06；
mp:156-158℃；
HRMS(ESI)m/z:HRMS-ESI(m/z):calcd for C24H35BrN3O,[M+H]+:460.1958,found
460.1961。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 14
3-(3-cyanophenyl)-2-propine carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 mmoles is added in the test tube of 25mL
You, bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, water one
Drip, be subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.Examine with TLC (thin layer chromatography)
After measured reaction terminates, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase,
Organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, crude product warp
Column chromatography purify obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixing molten
Agent, productivity 58%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in Figure 7 and Figure 8；Structural characterization data are as follows:
IR(KBr):3697,3092,2967,1759,1692,1551,1253,1018cm-1；
1H NMR(400MHz,CDCl3)δ7.78–7.67(m,2H),7.66–7.59(m,1H),1.69(s,9H)；
13C NMR(100MHz,CDCl3)δ149.21,140.11,138.52,132.91,132.28,131.70,129.08,128.66,
125.36,119.10,112.30,111.84,67.42,60.57,56.05,53.45,31.22,30.45,30.31；
mp:134-138℃；
HRMS(ESI)m/z:calcd for C25H34N4NaO,[M+Na]+:429.2625,found 429.2629。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 15
3-(3-acetylphenyl)-2-propine carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 milli is added in the test tube of 25mL
Mole, bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, water
One, it is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.With TLC (thin layer chromatography)
After detection reaction terminates, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase,
Organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, crude product warp
Column chromatography purify obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixing molten
Agent, productivity 70%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in Figure 9 and Figure 10；Structural characterization data are as follows:
IR(KBr):3692,2966,1686,1594,1461,1359,1230,1036cm-1；
1H NMR (400MHz, CDCl3) δ 8.05 (s, 1H), 7.74 (d, J=7.6Hz, 1H), 7.55 (d, J=7.6Hz, 1H),
7.41 (t, J=7.6Hz, 1H), 5.13 (s, 2H), 3.01 (s, 1H), 2.61 (s, 3H), 1.88 (s, 9H), 1.35 (s, 9H), 0.88 (s,
9H)；
13C NMR(100MHz,CDCl3)δ198.13,149.51,140.09,137.62,137.17,133.20,132.71,128.57,
128.08,125.35,125.03,113.10,67.55,60.45,55.85,53.39,31.32,30.50,30.32,26.62；
mp:133-136℃；
HRMS(ESI)m/z:calcd for C26H37N3NaO2,[M+Na]+:446.2778,found 446.2777。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 16
Addition 3-(4-iodophenyl)-2-propine carbonic ester 0.25 mM in the test tube of 25mL, tert-butyl isonitrile 0.80 mM,
Bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water,
It is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.Anti-with TLC (thin layer chromatography) detection
After should terminating, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic
Being dried removing water through anhydrous magnesium sulfate, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude product is through post layer
Analysis purification obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent,
Productivity 58%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as is illustrated by figs. 11 and 12；Structural characterization data are as follows:
IR(KBr):3699,3109,2827,1690,1556,1239,787cm-1；
1H NMR (400MHz, CDCl3) δ 7.63 (d, J=8.0Hz, 2H), 7.12 (d, J=8.0Hz, 2H), 5.08 (s, 2H),
2.94(s,1H),1.85(s,9H),1.34(s,9H),0.88(s,9H)；
13C NMR(100MHz,CDCl3)δ149.52,140.03,137.42,136.69,133.14,130.17,125.02,112.99,
90.14,67.55,60.50,55.99,53.41,31.35,30.53,30.32；
mp:171-173℃；
HRMS(ESI)m/z:calcd for C24H35IN3O,[M+H]+:508.1819,found 508.1818。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 17
3-(4 benzoic acid ethoxycarbonyl)-2-propine carbonic ester 0.25 mM, tert-butyl isonitrile 0.80 is added in the test tube of 25mL
MM, bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM,
One, water, is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.With TLC (thin layer chromatography)
After detection reaction terminates, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase,
Organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, crude product warp
Column chromatography purify obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixing molten
Agent, productivity 63%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in Figure 13 and Figure 14；Structural characterization data are as follows:
IR(KBr):3698,3106,2971,1694,1556,1364,1278,1011cm-1；
1H NMR (400MHz, CDCl3) δ 8.00 (d, J=7.6Hz, 2H), 7.45 (d, J=8Hz, 2H), 5.12 (s, 2H),
4.37 (q, J=6.8Hz, 2H), 3.04 (s, 1H), 1.87 (s, 9H), 1.40 (t, J=7.0Hz, 3H), 1.35 (s, 9H), 0.89 (s,
9H)；
13C NMR(100MHz,CDCl3)δ166.64,149.47,142.02,140.54,133.38,129.72,127.84,127.15,
125.27,113.29,67.65,60.74,60.62,56.18,53.43,31.33,30.51,30.26,14.35；
mp:140-142℃；
HRMS(ESI)m/z:calcd for C27H39N3NaO3,[M+Na]+:476.2884,found 476.2881。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 18
Addition 3-(2-naphthalene)-2-propine carbonic ester 0.25 mM in the test tube of 25mL, tert-butyl isonitrile 0.80 mM, double
Triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, so
Rear addition dimethyl sulfoxide 2 milliliters, as solvent, stirs 12 hours at room temperature.With TLC (thin layer chromatography) detection reaction
After end, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies
It is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude by column chromatography
Purification obtains target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, produce
Rate 65%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in Figure 15 and Figure 16；Structural characterization data are as follows:
IR(KBr):3702,2960,1684,1545,1451,1361,1210,1008cm-1；
1H NMR (400MHz, CDCl3) δ 7.87 (d, J=7.6Hz, 2H), 7.76 (d, J=8.4Hz, 1H), 7.50 7.44
(m, 3H), 7.37 (d, J=7.2Hz, 1H), 4.93 (q, J=13.6Hz, 2H), 1.92 (s, 9H), 1.37 (s, 9H), 0.66 (s, 9H)；
13C NMR(101MHz,CDCl3)δ150.17,141.68,135.09,134.44,133.98,132.07,128.56,127.59,
126.84,126.16,125.84,125.64,125.52,124.35,112.02,68.02,60.64,55.10,53.46,31.64,30.58,
29.89；
mp:118-120℃；
HRMS(ESI)m/z:calcd for C28H38N3O,[M+H]+:432.3009.,found 432.3017。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 19
Addition 3-(2-thiophene)-2-propine carbonic ester 0.25 mM in the test tube of 25mL, tert-butyl isonitrile 0.80 mM,
Bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water,
It is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.Anti-with TLC (thin layer chromatography) detection
After should terminating, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic
Being dried removing water through anhydrous magnesium sulfate, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude product is through post layer
Analysis purification obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent,
Productivity 74%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in Figure 17 and Figure 18；Structural characterization data are as follows:
IR(KBr):3457,2983,1762,1687,1480,1375,1242,1054cm-1；
1H NMR (400MHz, CDCl3) δ 7.14 (d, J=4.8Hz, 1H), 7.02 6.94 (m, 1H), 6.86 (d, J=2.8
Hz,1H),5.11(s,2H),3.04(s,1H),1.84(s,9H),1.34(s,9H),0.98(s,9H)；
13C NMR(100MHz,CDCl3)δ149.69,140.76,138.93,133.47,126.98,125.26,123.60,122.86,
107.99,67.64,60.75,56.06,53.40,31.30,30.53,30.06；
mp:98-100℃；
HRMS(ESI)m/z:calcd for C22H34N3OS,[M+H]+:388.2417,found 388.2417。
Infer that products therefrom obtains structure according to data above as follows:
Embodiment 20
Addition 3-hexin-2-methyl carbonate 0.25 mM in the test tube of 25mL, tert-butyl isonitrile 0.80 mM, double three
Phenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, then
Addition dimethyl sulfoxide 2 milliliters, as solvent, stirs 12 hours at room temperature.With TLC (thin layer chromatography) detection reaction knot
Shu Hou, pours reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic facies warp
Anhydrous magnesium sulfate is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography carries
The pure target product that obtains, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity
55%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as illustrated in figures 19 and 20；Structural characterization data are as follows:
IR(KBr):3698,3108,2968,1686,1561,1463,1363,1216cm-1；
1H NMR (400MHz, CDCl3) δ 5.30 (q, J=6.2Hz, 1H), 2.47 (dd, J=14.7,7.5Hz, 1H), 2.35
(dt, J=14.6,7.3Hz, 1H), 1.78 (s, 9H), 1.45 (d, J=6.4Hz, 3H), 1.32 (s, 9H), 1.13 (s, 9H), 1.09 (t, J
=7.6Hz, 3H)；
13C NMR(100MHz,CDCl3)δ149.93,139.71,138.05,124.51,114.00,75.17,59.61,54.72,
53.15,31.40,30.52,30.47,21.14,18.93,14.71；
mp:87-91℃；
HRMS(ESI)m/z:calcd for C21H38N3O,[M+H]+:348.3009,found 348.3013。
Infer that products therefrom obtains structure according to data above as follows
Embodiment 21
Addition 4-phenyl-3-crotonylene-methyl carbonate 0.25 mM in the test tube of 25mL, tert-butyl isonitrile 0.80 mM,
Bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water,
It is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.Anti-with TLC (thin layer chromatography) detection
After should terminating, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic
Being dried removing water through anhydrous magnesium sulfate, cross leaching liquid, after removing ethyl acetate under reduced pressure, obtain crude product, crude product is through post layer
Analysis purification obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent,
Productivity 72%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in figure 21 and figure；Structural characterization data are as follows:
IR(KBr):3693,2979,1761,1685,1581,1375,1242,1053cm-1；
1H NMR (400MHz, CDCl3) δ 7.34 7.27 (m, 4H), 7.18 (d, J=5.6Hz, 1H), 5.46 (q, J=5.9
Hz, 1H), 2.93 (s, 1H), 1.86 (s, 9H), 1.34 (s, 9H), 1.29 (d, J=6.4Hz, 3H), 0.83 (s, 9H)；
13C NMR(100MHz,CDCl3)δ149.49,140.08,137.70,136.71,129.10,128.29,125.58,124.50,
114.32,75.32,60.33,55.59,53.29,31.47,30.45,30.20,21.04；
mp:130-132℃；
HRMS(ESI)m/z:calcd for C25H38N3O,[M+H]+:396.3009,found 396.3009。
Infer that products therefrom obtains structure according to data above as follows
Embodiment 22
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, 1,1,3,3-tetramethyl normal-butyl isonitrile 0.80 milli is added in the test tube of 25mL
Mole, bi triphenyl phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, water
One, it is subsequently adding dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.With TLC (thin layer chromatography)
After detection reaction terminates, pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase,
Organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, crude product warp
Column chromatography purify obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixing molten
Agent, productivity 67%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as shown in figure 23 and figure 24；Structural characterization data are as follows:
IR(KBr):3450,2953,1762,1680,1489,1374,1241,1053cm-1；
1H NMR (400MHz, CDCl3) δ 7.35 7.27 (m, 4H), 7.17 (t, J=6.8Hz, 1H), 5.06 (s, 2H), 3.19
(s,1H),2.38(s,2H),1.97(s,6H),1.80(s,2H),1.39(s,8H),1.00(s,9H),0.93(s,9H),0.82(s,6H),
0.76(s,9H)；
13C NMR(100MHz,CDCl3)δ149.62,140.75,137.51,133.84,128.58,128.44,125.55,124.83,
114.35,67.18,63.85,60.32,57.39,56.43,54.37,53.09,31.93,31.90,31.85,31.63,31.35,30.95,
29.35；
mp:78-81℃；
HRMS(ESI)m/z:calcd for C36H60N3O,[M+H]+:550.4731,found 550.4734。
Infer that products therefrom obtains structure according to data above as follows
Embodiment 23
Phenylpropyl alcohol alkynyl carbonic ester 0.25 mM, adamantyl isonitrile 0.80 mM, double triphens are added in the test tube of 25mL
Base phosphorus palladium chloride 0.0125 mM, triphenyl phosphorus 0.025 mM, cesium fluoride 0.5 mM, one, water, then add
Enter dimethyl sulfoxide 2 milliliters as solvent, at room temperature stirring 12 hours.Terminate with TLC (thin layer chromatography) detection reaction
After, to pour reactant liquor into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, take upper organic phase, organic facies is through nothing
Water magnesium sulfate is dried removing water, crosses leaching liquid, after removing ethyl acetate under reduced pressure, obtains crude product, and crude by column chromatography purifies
Obtain target product, column chromatography eluent used be volume ratio be the petroleum ether of 100:1: ethyl acetate mixed solvent, productivity
45%.
The hydrogen spectrogram of the present embodiment products therefrom and carbon spectrogram are the most as illustrated in figs. 25 and 26；Structural characterization data are as follows:
IR(KBr):3448,2912,2853,1764,1676,1457,1373,1243,1056cm-1；
1H NMR (400MHz, CDCl3) δ 7.31 (q, J=7.8Hz, 4H), 7.15 (t, J=6.8Hz, 1H), 5.09 (s, 2H),
2.99 (s, 1H), 2.73 (s, 6H), 2.17 (s, 2H), 2.04 (d, J=11.9Hz, 9H), 1.88 (d, J=13.2Hz, 6H), 1.69
(dd, J=26.4,12.3Hz, 9H), 1.56 (s, 2H), 1.47 (d, J=12,2H), 1.41 (d, J=10.9Hz, 9H)；
13C NMR(100MHz,CDCl3)δ150.04,139.49,137.25,133.78,128.43,128.32,125.31,
124.34,114.12,67.66,62.19,56.28,54.48,43.51,42.56,36.99,36.34,36.12,30.70,30.09,29.91；
mp:249-252℃；
HRMS(ESI)m/z:calcd for C42H54N3O,[M+H]+:616.4261,found 616.4261。
Infer that products therefrom obtains structure according to data above as follows
Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention being not restricted to the described embodiments,
The change made under other any spirit without departing from the present invention and principle, modify, substitute, combine, simplify, all should
For equivalence substitute mode, within being included in protection scope of the present invention.
Claims (10)
1. the nitrogen-containing heterocycle compound of a pyrrolo-furan, it is characterised in that: described compound has the knot shown in formula (1)
Structure formula:
In formula, R1For H, alkyl, naphthyl, thienyl, phenyl or F, Cl, Br, I, alkyl, alkoxyl, itrile group, ester
The substituted phenyl of base；R2For the tert-butyl group, cyclohexyl, 1,1,3,3-tetramethyl-normal-butyl or adamantyl；R3For H or alkyl.
2. the synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan described in claim 1, it is characterised in that include with
Lower step:
In reaction vessel, add alkynyl carbonic ester, metal palladium catalyst, part, alkali, water and solvent, add isonitrile,
0～100 DEG C of stirring reaction 8～16 hours, after question response terminates, pours reactant liquor into separatory funnel, by water and ethyl acetate
Mixed solvent extracts, and takes upper organic phase, and organic facies is dried removing water through anhydrous magnesium sulfate, crosses leaching liquid, and decompression is steamed
After ethyl acetate, obtaining crude product, crude by column chromatography purifies the nitrogen-containing heterocycle compound obtaining described pyrrolo-furan.
The synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan the most according to claim 2, it is characterised in that:
Described alkynyl carbonic ester is phenylpropyl alcohol alkynyl carbonic ester, 3-(2-aminomethyl phenyl)-2-propine carbonic ester, 3-(2-bromophenyl)-2-propine carbon
Acid esters, 3-(3-cyanophenyl)-2-propine carbonic ester, 3-(3-acetylphenyl)-2-propine carbonic ester, 3-(4-iodophenyl)-2-propine carbon
Acid esters, 3-(4 benzoic acid ethoxycarbonyl)-2-propine carbonic ester, 3-(2-naphthalene)-2-propine carbonic ester, 3-(2-thiophene)-2-propine carbonic ester,
3-hexin-2-methyl carbonate, 4-phenyl-3-crotonylene-methyl carbonate or phenylpropyl alcohol alkynyl carbonic ester.
The synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan the most according to claim 2, it is characterised in that:
Described isonitrile is tert-butyl isonitrile, 1,1,3,3-tetramethyl normal-butyl isonitrile or adamantyl isonitrile.
The synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan the most according to claim 2, it is characterised in that:
Described metal palladium catalyst is Palladous chloride., palladium iodide, palladium bromide, palladium, dichlorodiethyl nitrile palladium, palladium trifluoroacetate or double three
Phenyl phosphorus palladium chloride.
The synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan the most according to claim 2, it is characterised in that:
Described part is 1,10-phenanthrene quinoline, adjacent luxuriant and rich with fragrance quinoline, thricyclohexyl phosphorus, triphenyl phosphorus, tri-tert phosphorus, 2, and 2 '-bipyridyl,
4,4 '-bipyridyl or three (o-methyl-phenyl-) phosphorus.
The synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan the most according to claim 2, it is characterised in that:
Described alkali is triethylamine, pyridine, potassium carbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, tert-butyl alcohol lithium, potassium tert-butoxide, uncle
Sodium butoxide, sodium acetate, Sodium ethylate, cesium fluoride or cesium carbonate.
The synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan the most according to claim 2, it is characterised in that:
Described solvent is DMF, N,N-dimethylacetamide, toluene, Isosorbide-5-Nitrae-dioxane, dimethyl sulfoxide,
1,2-dichloroethanes, acetonitrile or oxolane.
9., according to the synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan described in any one of claim 2～8, it is special
Levy and be: the addition of described metal palladium catalyst is (0.001～3) with the mol ratio of alkynyl carbonic ester: 1, with the mol ratio of water
For (0.001～1): 1, it is (0.001～4) with the mol ratio of alkali: 1, is (0.005～3) with the mol ratio of part: 1；Described
The addition of alkynyl carbonic ester and the mol ratio of isonitrile are (0.01～1): 1.
The synthetic method of the nitrogen-containing heterocycle compound of a kind of pyrrolo-furan the most according to claim 2, it is characterised in that:
Described column chromatography purifies the mixed solvent using eluent to be petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is
1～(100:1).
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| CN106977524A (en) * | 2017-04-12 | 2017-07-25 | 扬州大学 | A kind of synthetic method of phenanthro- furans and azoles |
| CN110366449A (en) * | 2017-02-28 | 2019-10-22 | 国立大学法人九州大学 | Hydrosilylation reactions, hydrogenation and hydrogen silane reduction reaction catalyst |
| CN112592352A (en) * | 2020-12-23 | 2021-04-02 | 华南理工大学 | Polysubstituted benzothienopyridine compound and preparation method thereof |
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| US5389641A (en) * | 1991-04-16 | 1995-02-14 | Takeda Chemical Industries, Ltd. | Fused heterocyclic compounds, having angiotensin II antagonistic activity |
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| CN110366449A (en) * | 2017-02-28 | 2019-10-22 | 国立大学法人九州大学 | Hydrosilylation reactions, hydrogenation and hydrogen silane reduction reaction catalyst |
| CN106977524A (en) * | 2017-04-12 | 2017-07-25 | 扬州大学 | A kind of synthetic method of phenanthro- furans and azoles |
| CN112592352A (en) * | 2020-12-23 | 2021-04-02 | 华南理工大学 | Polysubstituted benzothienopyridine compound and preparation method thereof |
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