CN105732648B - The nitrogen-containing heterocycle compound and synthetic method of a kind of pyrrolo- furans - Google Patents
The nitrogen-containing heterocycle compound and synthetic method of a kind of pyrrolo- furans Download PDFInfo
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- CN105732648B CN105732648B CN201610074386.XA CN201610074386A CN105732648B CN 105732648 B CN105732648 B CN 105732648B CN 201610074386 A CN201610074386 A CN 201610074386A CN 105732648 B CN105732648 B CN 105732648B
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- SLDGDTLKVFFNGH-SLMZUGIISA-N CC(C)(C)Nc([n](C(C)(C)C)c1c2CO/C1=N\C(C)(C)C)c2-c1cc(C#N)ccc1 Chemical compound CC(C)(C)Nc([n](C(C)(C)C)c1c2CO/C1=N\C(C)(C)C)c2-c1cc(C#N)ccc1 SLDGDTLKVFFNGH-SLMZUGIISA-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
Abstract
The invention belongs to technical field of organic synthesis, the nitrogen-containing heterocycle compound and synthetic method of a kind of pyrrolo- furans are disclosed.The compound has in the general structure shown in formula (1), formula, R1For H, alkyl, naphthyl, thienyl, phenyl or F, Cl, Br, I, alkyl, alkoxy, itrile group, the phenyl of ester group substitution；R2For the tert-butyl group, cyclohexyl, 1,1,3,3 tetramethyl normal-butyl or adamantyl；R3For H or alkyl.The synthetic method is：Alkynyl carbonic ester, metal palladium catalyst, part, alkali, water and solvent are added in the reactor, add isonitrile, 0~100 DEG C of stirring reaction 8~16 hours, reaction product obtains the nitrogen-containing heterocycle compound of the pyrrolo- furans through extraction, separation, purifying.Synthesising method reacting condition of the invention is gentle, safe operation is simple, raw material is cheap and easy to get, functional group adaptability is good, good yields, has a good application prospect.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of nitrogen-containing heterocycle compound of pyrrolo- furans and conjunction
Into method.
Background technology
Azaaromatics, intramolecular contains larger conjugated system and strong cyclic voltammetry method, this spy
Different rigid condensed cyclic structure makes nitrogen-containing hetero cyclics show many unique performances and bioactivity, photoelectric material,
Dyestuff, medicine, Supramolecular Recognition etc. are multi-field to have potential extensive use.What is more important heterocycle compound be easy into
Row structural modification, can synthesize important functional molecular, as very active research field in the last few years.
The nitrogen-containing hetero cyclics of pyrrolo- furans, pyrroles is turned into after slightly modifying by the imines hydrolysis on furan nucleus
And five-membered ring lactone, can be synthesized as reaction intermediate some antitumor, anticancer medicines (Amit Kumar Jana,
Dipakranjan Mal.Chem.Commun,2010,46,4411-4413；).Such as generating structure diversity and bio-diversity
Carbazole alkaloid (Joyeeta 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 one
Kind of condition is gentleer, and Atom economy is good, and raw material is simple and easy to get, the change of the nitrogen heterocyclic ring class of easy to operate pyrrolo- furans
The construction method of compound, is the target that researcher in this field makes great efforts.
The content of the invention
Based on above prior art, primary and foremost purpose of the invention is to provide a kind of nitrogen heterocyclic ring chemical combination of pyrrolo- furans
Thing.
Another object of the present invention is to provide a kind of synthetic method of the nitrogen-containing heterocycle compound of above-mentioned pyrrolo- furans.
The object of the invention is achieved through the following technical solutions：
A kind of nitrogen-containing heterocycle compound of pyrrolo- furans, with the general structure shown in formula (1)：
Formula (1),
In formula, R1For H, alkyl, naphthyl, thienyl, phenyl or F, Cl, Br, I, alkyl, alkoxy, itrile group, ester group substitution
Phenyl；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- furans, comprises the following steps：
In reaction vessels, alkynyl carbonic ester, metal palladium catalyst, part, alkali, water and solvent are added, isonitrile is added,
0~100 DEG C of stirring reaction 8~16 hours, after question response terminates, separatory funnel is poured into by reaction solution, with water and ethyl acetate
Mixed solvent is extracted, and takes upper organic phase, and organic phase is dried through anhydrous magnesium sulfate and removes water, filters to take liquid, and decompression is steamed
After ethyl acetate, crude product is obtained, crude by column chromatography purifies the nitrogen-containing heterocycle compound for obtaining the pyrrolo- furans.
Above-mentioned reaction is shown below：
Preferably, described alkynyl carbonic ester be phenylpropyl alcohol alkynyl carbonic ester, 3- (2- aminomethyl phenyls) -2- propine carbonic esters,
3- (2- bromophenyls) -2- propine carbonic esters, 3- (3- cyanophenyls) -2- propine carbonic esters, 3- (3- acetylphenyls) -2- propine
Carbonic ester, 3- (4- iodophenyls) -2- propine carbonic esters, 3- (4 benzoic acid ethoxycarbonyl) -2- propine carbonic esters, 3- (2- naphthalenes) -2-
Propine carbonic ester, 3- (2- thiophene) -2- propine carbonic esters, 3- hexin -2- methyl carbonates, 4- phenyl -3- crotonylenes-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, the metal palladium catalyst is palladium bichloride, palladium iodide, palladium bromide, palladium, dichlorodiethyl nitrile palladium, three
Fluoroacetic acid palladium or bi triphenyl phosphorus palladium chloride.
Preferably, the part be 1,10- ferrosins, phenanthroline, thricyclohexyl phosphorus, triphenyl phosphorus, tri-tert phosphorus,
2,2 '-bipyridyl, 4,4 '-bipyridyl or three (o-methyl-phenyl) phosphorus.
Preferably, the alkali be triethylamine, pyridine, potassium carbonate, sodium carbonate, sodium hydroxide, saleratus, tert-butyl alcohol lithium,
Potassium tert-butoxide, sodium tert-butoxide, sodium acetate, caustic alcohol, cesium fluoride or cesium carbonate.
Preferably, described solvent is DMF, DMA, toluene, Isosorbide-5-Nitrae-dioxy six
Ring, dimethyl sulfoxide (DMSO), 1,2- dichloroethanes, acetonitrile or tetrahydrofuran.
Preferably, the addition of the metal palladium catalyst and the mol ratio of alkynyl carbonic ester are (0.001~3):1, with
The mol ratio of water is (0.001~1):1, the mol ratio with alkali is (0.001~4):1, with the mol ratio of part for (0.005~
3):1。
Preferably, the addition of the alkynyl carbonic ester and the mol ratio of isonitrile are (0.01~1):1.
Preferably, column chromatography purification is using the mixed solvent that eluent is petroleum ether and ethyl acetate, petroleum ether and
The volume ratio of ethyl acetate is 1~(100:1).
Relative to prior art, the invention has the advantages that and beneficial effect：
A kind of utilization propargyl carbonic ester of the present invention and isonitrile synthesize the nitrogen-containing heterocycle compound of pyrrolo- furans, react bar
Part is gentle, and safe operation is simple, raw material is cheap and easy to get, functional group adaptability is good, good yields.Isonitrile is under the catalytic action of palladium
Polymolecular insertion, the relatively new nitrogenous heterocyclic skeleton of composite structure, with higher Atom economy can be realized.
Brief description of the drawings
Fig. 1 and Fig. 2 are the hydrogen spectrogram and carbon spectrogram of embodiment 1-11 products therefroms respectively；
Fig. 3 and Fig. 4 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 12 respectively；
Fig. 5 and Fig. 6 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 13 respectively；
Fig. 7 and Fig. 8 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 14 respectively；
Fig. 9 and Figure 10 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 15 respectively；
Figure 11 and Figure 12 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 16 respectively；
Figure 13 and Figure 14 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 17 respectively；
Figure 15 and Figure 16 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 18 respectively；
Figure 17 and Figure 18 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 19 respectively；
Figure 19 and Figure 20 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 20 respectively；
Figure 21 and Figure 22 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 21 respectively；
Figure 23 and Figure 24 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 22 respectively；
Figure 25 and Figure 26 are the hydrogen spectrogram and carbon spectrogram of the products therefrom of embodiment 23 respectively.
Embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited
In this.
Embodiment 1
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, Ran Houjia
Enter 2 milliliters of acetonitrile as solvent, in stirring 2 hours at 90 DEG C.After being terminated with TLC (thin-layered chromatography) detection reactions, it will react
Liquid pours into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is dry through anhydrous magnesium sulfate
It is dry to remove water, filter to take liquid, remove under reduced pressure after ethyl acetate, obtain crude product, crude by column chromatography purification obtains target production
Thing, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 48%.
Embodiment 2
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, Ran Houjia
Enter 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, in stirring 2 hours at 90 DEG C.After being terminated with TLC (thin-layered chromatography) detection reactions,
Reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase is taken, organic phase is through anhydrous sulphur
Sour magnesium, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, and crude by column chromatography purification is obtained
Target product, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 55%.
Embodiment 3
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, chlorination are added in 25mL test tube
0.0125 mM of palladium, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, and then adds dimethyl sulfoxide (DMSO) 2
Milliliter is as solvent, in stirring 2 hours at 90 DEG C.After being terminated with TLC (thin-layered chromatography) detection reactions, reaction solution is poured into point
Liquid funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is dried through anhydrous magnesium sulfate and removed
Water, liquid is filtered to take, removed under reduced pressure after ethyl acetate, obtain crude product, crude by column chromatography purification obtains target product, used
Column chromatography eluent be that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 38%.
Embodiment 4
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, acetic acid are added in 25mL test tube
0.0125 mM of palladium, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, and then adds dimethyl sulfoxide (DMSO) 2
Milliliter is as solvent, in stirring 2 hours at 90 DEG C.After being terminated with TLC (thin-layered chromatography) detection reactions, reaction solution is poured into point
Liquid funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is dried through anhydrous magnesium sulfate and removed
Water, liquid is filtered to take, removed under reduced pressure after ethyl acetate, obtain crude product, crude by column chromatography purification obtains target product, used
Column chromatography eluent be that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 42%.
Embodiment 5
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, the milli of 1,8- diazabicylo, 11 carbon -7- alkene 0.5
Mole, water one drips, and 2 milliliters of dimethyl sulfoxide (DMSO) is then added as solvent, in stirring 2 hours at 90 DEG C.With TLC (thin-layer chromatographys
Method) detection reaction terminate after, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper strata to have
Machine phase, organic phase is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, thick production
Thing obtains target product through column chromatography purification, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate
Mixed solvent, yield 38%.
Embodiment 6
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of potassium carbonate, water one drips, Ran Houjia
Enter 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, in stirring 2 hours at 90 DEG C.After being terminated with TLC (thin-layered chromatography) detection reactions,
Reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase is taken, organic phase is through anhydrous sulphur
Sour magnesium, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, and crude by column chromatography purification is obtained
Target product, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 27%.
Embodiment 7
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of pyridine, water one drips, and then adds
2 milliliters of dimethyl sulfoxide (DMSO) is as solvent, in stirring 2 hours at 90 DEG C., will after being terminated with TLC (thin-layered chromatography) detection reactions
Reaction solution pours into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is through anhydrous slufuric acid
Magnesium, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, and crude by column chromatography purification obtains mesh
Product is marked, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 22%.
Embodiment 8
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of thricyclohexyl phosphorus, 0.5 mM of cesium fluoride, water one drips, then
2 milliliters of dimethyl sulfoxide (DMSO) is added as solvent, in stirring 2 hours at 90 DEG C.Terminated with TLC (thin-layered chromatography) detection reactions
Afterwards, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is through nothing
Water magnesium sulfate, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, crude by column chromatography purification
Target product is obtained, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield
43%.
Embodiment 9
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 1,10- 0.025 mM of ferrosin, 0.5 mM of potassium carbonate, water one drips, then
2 milliliters of dimethyl sulfoxide (DMSO) is added as solvent, in stirring 2 hours at 90 DEG C.Terminated with TLC (thin-layered chromatography) detection reactions
Afterwards, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is through nothing
Water magnesium sulfate, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, crude by column chromatography purification
Target product is obtained, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield
35%.
Embodiment 10
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, Ran Houjia
Enter 2 milliliters of acetonitrile as solvent, in stirring 2 hours at 50 DEG C.After being terminated with TLC (thin-layered chromatography) detection reactions, it will react
Liquid pours into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is dry through anhydrous magnesium sulfate
It is dry to remove water, filter to take liquid, remove under reduced pressure after ethyl acetate, obtain crude product, crude by column chromatography purification obtains target production
Thing, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 50%.
Embodiment 11
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 0.80 mM of tert-butyl isonitrile, double three are added in 25mL test tube
0.0125 mM of phenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, Ran Houjia
Enter 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stir 12 hours at room temperature.After being terminated with TLC (thin-layered chromatography) detection reactions,
Reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase is taken, organic phase is through anhydrous sulphur
Sour magnesium, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, and crude by column chromatography purification is obtained
Target product, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield 75%.
Hydrogen spectrogram and carbon the spectrogram difference of embodiment 1-11 products therefroms are as depicted in figs. 1 and 2；Structural characterization data are as follows
It is shown：
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 the structure of products therefrom is as follows according to data above：
Embodiment 12
0.25 mM of 3- (2- aminomethyl phenyls) -2- propine carbonic ester, tert-butyl isonitrile are added in 25mL test tube
0.80 mM, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, the mmoles of cesium fluoride 0.5
You, water one drips, and then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.With TLC (thin-layer chromatographys
Method) detection reaction terminate after, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper strata to have
Machine phase, organic phase is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, thick production
Thing obtains target product through column chromatography purification, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate
Mixed solvent, yield 55%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in Figure 3 and Figure 4；The following institute of structural characterization data
Show：
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
0.25 mM of 3- (2- bromophenyls) -2- propine carbonic ester, tert-butyl isonitrile 0.80 are added in 25mL test tube
MM, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water
One drop, then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.Detected with TLC (thin-layered chromatography)
After reaction terminates, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase is taken, has
Machine is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, crude product is through post
Chromatographic purification obtains target product, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixing is molten
Agent, yield 58%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in Figure 5 and Figure 6；The following institute of structural characterization data
Show：
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
=6.4Hz, 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,
found460.1961。
Infer that products therefrom obtains structure according to data above as follows：
Embodiment 14
0.25 mM of 3- (3- cyanophenyls) -2- propine carbonic ester, tert-butyl isonitrile are added in 25mL test tube
0.80 mM, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, the mmoles of cesium fluoride 0.5
You, water one drips, and then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.With TLC (thin-layer chromatographys
Method) detection reaction terminate after, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper strata to have
Machine phase, organic phase is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, thick production
Thing obtains target product through column chromatography purification, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate
Mixed solvent, yield 58%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in Figure 7 and Figure 8；The following institute of structural characterization data
Show：
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
0.25 mM of 3- (3- acetylphenyls) -2- propine carbonic ester, tert-butyl isonitrile are added in 25mL test tube
0.80 mM, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, the mmoles of cesium fluoride 0.5
You, water one drips, and then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.With TLC (thin-layer chromatographys
Method) detection reaction terminate after, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper strata to have
Machine phase, organic phase is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, thick production
Thing obtains target product through column chromatography purification, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate
Mixed solvent, yield 70%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in Figure 9 and Figure 10；Structural characterization data are as follows
It is shown：
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
0.25 mM of 3- (4- iodophenyls) -2- propine carbonic ester, tert-butyl isonitrile 0.80 are added in 25mL test tube
MM, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water
One drop, then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.Detected with TLC (thin-layered chromatography)
After reaction terminates, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase is taken, has
Machine is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, crude product is through post
Chromatographic purification obtains target product, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixing is molten
Agent, yield 58%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as is illustrated by figs. 11 and 12；Structural characterization data are as follows
It is shown：
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
0.25 mM of 3- (4 benzoic acid ethoxycarbonyl) -2- propine carbonic ester is added in 25mL test tube, the tert-butyl group is different
0.80 mM of nitrile, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, the mmoles of cesium fluoride 0.5
You, water one drips, and then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.With TLC (thin-layer chromatographys
Method) detection reaction terminate after, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper strata to have
Machine phase, organic phase is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, thick production
Thing obtains target product through column chromatography purification, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate
Mixed solvent, yield 63%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in Figure 13 and Figure 14；Structural characterization data are as follows
It is shown：
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
0.25 mM of 3- (2- naphthalenes) -2- propine carbonic ester, the mmoles of tert-butyl isonitrile 0.80 are added in 25mL test tube
You, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips,
Then 2 milliliters of dimethyl sulfoxide (DMSO) is added as solvent, is stirred 12 hours at room temperature.Detected and reacted with TLC (thin-layered chromatography)
After end, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase, organic phase is taken
Dried through anhydrous magnesium sulfate and remove water, filter to take liquid, removed under reduced pressure after ethyl acetate, obtain crude product, crude by column chromatography
Purification obtains target product, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent,
Yield 65%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in Figure 15 and Figure 16；Structural characterization data are as follows
It is shown：
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
0.25 mM of 3- (2- thiophene) -2- propine carbonic ester, the milli of tert-butyl isonitrile 0.80 are added in 25mL test tube
Mole, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one
Drop, then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.It is anti-with TLC (thin-layered chromatography) detections
After should terminating, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase is taken, it is organic
Dried through anhydrous magnesium sulfate and remove water, filter to take liquid, removed under reduced pressure after ethyl acetate, obtain crude product, crude product is through post layer
Analysis purification obtains target product, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixing is molten
Agent, yield 74%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in Figure 17 and Figure 18；Structural characterization data are as follows
It is shown：
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=
2.8Hz,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
0.25 mM of 3- hexin -2- methyl carbonates are added in 25mL test tube, 0.80 mM of tert-butyl isonitrile is double
0.0125 mM of triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, then
2 milliliters of dimethyl sulfoxide (DMSO) is added as solvent, is stirred 12 hours at room temperature.Terminated with TLC (thin-layered chromatography) detection reactions
Afterwards, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is through nothing
Water magnesium sulfate, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, crude by column chromatography purification
Target product is obtained, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield
55%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as illustrated in figures 19 and 20；Structural characterization data are as follows
It is shown：
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
4- phenyl -3- crotonylenes -0.25 mM of methyl carbonate, the milli of tert-butyl isonitrile 0.80 are added in 25mL test tube
Mole, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one
Drop, then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.It is anti-with TLC (thin-layered chromatography) detections
After should terminating, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, upper organic phase is taken, it is organic
Dried through anhydrous magnesium sulfate and remove water, filter to take liquid, removed under reduced pressure after ethyl acetate, obtain crude product, crude product is through post layer
Analysis purification obtains target product, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixing is molten
Agent, yield 72%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in figure 21 and figure；Structural characterization data are as follows
It is shown：
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=
5.9Hz, 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
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester, 1,1,3,3- tetramethyl normal-butyl isonitrile are added in 25mL test tube
0.80 mM, 0.0125 mM of bi triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, the mmoles of cesium fluoride 0.5
You, water one drips, and then adds 2 milliliters of dimethyl sulfoxide (DMSO) as solvent, stirs 12 hours at room temperature.With TLC (thin-layer chromatographys
Method) detection reaction terminate after, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper strata to have
Machine phase, organic phase is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, is obtained crude product, thick production
Thing obtains target product through column chromatography purification, and column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate
Mixed solvent, yield 67%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as shown in figure 23 and figure 24；Structural characterization data are as follows
It is shown：
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
0.25 mM of phenylpropyl alcohol alkynyl carbonic ester is added in 25mL test tube, 0.80 mM of adamantyl isonitrile is double
0.0125 mM of triphenyl phosphorus palladium chloride, 0.025 mM of triphenyl phosphorus, 0.5 mM of cesium fluoride, water one drips, then
2 milliliters of dimethyl sulfoxide (DMSO) is added as solvent, is stirred 12 hours at room temperature.Terminated with TLC (thin-layered chromatography) detection reactions
Afterwards, reaction solution is poured into separatory funnel, with water and the mixed extractant solvent of ethyl acetate, takes upper organic phase, organic phase is through nothing
Water magnesium sulfate, which is dried, to be removed water, filters to take liquid, is removed under reduced pressure after ethyl acetate, obtains crude product, crude by column chromatography purification
Target product is obtained, column chromatography eluent used is that volume ratio is 100:1 petroleum ether:Ethyl acetate mixed solvent, yield
45%.
Hydrogen spectrogram and carbon the spectrogram difference of the present embodiment products therefrom are as illustrated in figs. 25 and 26；Structural characterization data are as follows
It is shown：
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 preferably embodiment, but embodiments of the present invention are not by above-described embodiment of the invention
Limitation, other any Spirit Essences without departing from the present invention and the change made under principle, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (6)
1. a kind of synthetic method of the nitrogen-containing heterocycle compound of pyrrolo- furans, it is characterised in that：The compound has formula (1)
Shown general structure：
In formula, R1For H, alkyl, naphthyl, thienyl, phenyl or F, Cl, Br, I, alkyl, alkoxy, itrile group, the benzene of ester group substitution
Base；R2For the tert-butyl group, cyclohexyl, 1,1,3,3- tetramethyl-normal-butyl or adamantyl；R3For H or alkyl；
The synthetic method comprises the following steps：
In reaction vessel, alkynyl carbonic ester, metal palladium catalyst, part, alkali, water and solvent are added, isonitrile is added, 0~
100 DEG C of stirring reactions 8~16 hours, after question response terminates, separatory funnel are poured into by reaction solution, with the mixing of water and ethyl acetate
Solvent is extracted, and takes upper organic phase, and organic phase is dried through anhydrous magnesium sulfate to be removed water, filters to take liquid, removes second under reduced pressure
After acetoacetic ester, crude product is obtained, crude by column chromatography purifies the nitrogen-containing heterocycle compound for obtaining the pyrrolo- furans；
The metal palladium catalyst is palladium bichloride, palladium iodide, palladium bromide, palladium, dichlorodiethyl nitrile palladium, palladium trifluoroacetate or double
Triphenyl phosphorus palladium chloride；The part is 1,10- ferrosins, phenanthroline, thricyclohexyl phosphorus, triphenyl phosphorus, tri-tert
Phosphorus, 2,2 '-bipyridyl, 4,4 '-bipyridyl or three (o-methyl-phenyl) phosphorus；The alkali is triethylamine, pyridine, potassium carbonate, carbonic acid
Sodium, sodium hydroxide, saleratus, tert-butyl alcohol lithium, potassium tert-butoxide, sodium tert-butoxide, sodium acetate, caustic alcohol, cesium fluoride or cesium carbonate.
2. a kind of synthetic method of the nitrogen-containing heterocycle compound of pyrrolo- furans according to claim 1, it is characterised in that：
Described alkynyl carbonic ester is phenylpropyl alcohol alkynyl carbonic ester, 3- (2- aminomethyl phenyls) -2- propine carbonic esters, 3- (2- bromophenyls) -2-
Propine carbonic ester, 3- (3- cyanophenyls) -2- propine carbonic esters, 3- (3- acetylphenyls) -2- propine carbonic esters, 3- (4- iodine
Phenyl) -2- propine carbonic esters, 3- (4 benzoic acid ethoxycarbonyl) -2- propine carbonic esters, 3- (2- naphthalenes) -2- propine carbonic esters, 3-
(2- thiophene) -2- propine carbonic esters, 3- hexin -2- methyl carbonates, 4- phenyl -3- crotonylenes-methyl carbonate or phenylpropyl alcohol alkynyl carbon
Acid esters.
3. a kind of synthetic method of the nitrogen-containing heterocycle compound of pyrrolo- furans according to claim 1, it is characterised in that：
Described isonitrile is tert-butyl isonitrile, 1,1,3,3- tetramethyl normal-butyl isonitrile or adamantyl isonitrile.
4. a kind of synthetic method of the nitrogen-containing heterocycle compound of pyrrolo- furans according to claim 1, it is characterised in that：
Described solvent be DMF, DMA, toluene, Isosorbide-5-Nitrae-dioxane, dimethyl sulfoxide (DMSO), 1,
2- dichloroethanes, acetonitrile or tetrahydrofuran.
5. a kind of synthetic method of the nitrogen-containing heterocycle compound of pyrrolo- furans according to any one of Claims 1 to 4, its
It is characterised by：The addition of the metal palladium catalyst is (0.001~3) with the mol ratio of alkynyl carbonic ester:1, with rubbing for water
You are than being (0.001~1):1, the mol ratio with alkali is (0.001~4):1, the mol ratio with part is (0.005~3):1；Institute
It is (0.01~1) to state the addition of alkynyl carbonic ester and the mol ratio of isonitrile:1.
6. a kind of synthetic method of the nitrogen-containing heterocycle compound of pyrrolo- furans according to claim 1, it is characterised in that：
The column chromatography purification uses the volume ratio that eluent is petroleum ether and the mixed solvent of ethyl acetate, petroleum ether and ethyl acetate
For (1~100):1.
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