CN104987343A - A method for compounding derivatives of bisthiophenes - Google Patents
A method for compounding derivatives of bisthiophenes Download PDFInfo
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- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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Abstract
The invention discloses derivatives of bisthiophenes and a preparation method thereof. The derivatives of bisthiophenes are obtained by reacting thienothiophene anthranilonitrile with a carbonyl compound, the general formula of the molecular structure is as shown in the image, 3,4-diamino-thieno-[2,3-b]thiophene-2,5-dinitrile is taken as a raw material, and reacts with aldehyde or ketone of a carbonyl compound under the alkaline condition to compound a series of derivatives of bisthiophenes. The method has the advantages of simple operational process, mild reaction condition, high yield, good reaction selectivity and the like.
Description
(1) technical field
The invention belongs to organic chemistry filed, particularly relate to a kind of two Thienopyrimidine ketone derivatives, specifically a kind of method preparing two Thienopyrimidine ketone derivatives.
(2) background technology
Many fused heterocyclic compounds are the compounds that a class has extensive use, particularly in medicine and pesticide field, have very important impact.At field of medicaments, because it has good biological activity mostly, as antitumor (Heterocycles, 1997, 46:541-546), hypotensive (Bioorg.Med.Chem., 2009, 17 (6): 2351-2359), antibacterial (J Med Chem, 2010, 53 (9): 3558-3565), anti-inflammatory (Pharm.Chem.J., 1995, 29 (2): 124-126) and anti-malarial (Eur.J.Med.Chem., 2004, 39 (1): 59-67) isoreactivity, organic chemistry and pharmaceutical chemical study hotspot (chemical research are become, 2001, 22 (6): 85-95).Some many fused heterocyclic compounds also can be used as phosphodiesterase 1 (PDEl) (Bioorg.Med.Chem., 2009,17 (19): 6796-6802) and the inhibitor (J.Med.Chem. of phosphodiesterase 7 (PDE7), 2014,57:9844-9854).At pesticide field, many fused heterocyclic compounds class weedicide and sterilant because of its mostly have efficiently, the feature such as low toxicity, Environmental compatibility are good, dominant position (novel pesticide journal, 2000,2,1-10) will be occupy in pesticide research.In addition, many fused heterocyclic compounds also have important application (printing during chemical industry, 2006,20 (2): 58-62) in dyestuff etc.
Wherein, be many fused heterocyclic compounds that a class has applications well prospect containing thienothiophene structural compounds, at present, thienothiophene derivative is mainly used in medicine, agricultural chemicals, conductive polymers, liquid and cage type crystal, organic conductor and superconductor, photosensitive receptor, photoelectron material (non-linear optical chromophore), dyestuff etc. (Adv.Heterocycl.Chem.2006,90:125-203.) such as aspects.
At present, the method for the two Thienopyrimidine ketone compounds of synthesis mainly contains following three kinds: 1) with containing isocyano-thiophene derivant for raw material is through intramolecular cyclocondensation.Such reaction substrate universality is poor.2) with the adjacent amino amides of thienothiophene for raw material, with reactive ketone under acetum.Such post-reaction treatment aspect is more loaded down with trivial details.3) with thienothiophene o-amino-acid ester for raw material, after generating oxazinone with anhydride reaction, then react with aminocompound further.This reactions steps is many, and aftertreatment is more loaded down with trivial details.
(3) summary of the invention
The invention provides the method for the two Thienopyrimidine ketone derivatives of a kind of preparation newly.Namely 3,4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile and ketone or aldehyde reaction synthesising target compound is adopted.Reaction expression is:
Wherein:
R
1for hydrogen, alkyl, aryl, R
2for hydrogen, alkyl, aryl etc.
The method of the two Thienopyrimidine ketone derivatives of preparation of the present invention comprises the steps:
(1) by 3,4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile join in reaction medium, add ketone (or aldehyde) and catalyzer afterwards.
(2) in heating unit, reactant reacts to stirred at reflux condition in room temperature, by thin-layer chromatography detection reaction progress.
(3), after reaction terminates, vacuum rotary steam removes most of solvent, is cooled to room temperature, and adding distil water, suction filtration, is washed to neutrality, obtains solid.
(4) recrystallization or column chromatography purification are carried out to the thick product that step 3 obtains, obtain pure target compound.
Method is more preferably:
(1) by 3,4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile joins in the reaction medium of 1 ~ 500 times, and reaction medium is more excellent but be not limited only to the alcohols such as aldehyde, ketone, toluene, dimethyl sulfoxide (DMSO), dioxane, halogenated alkane, ethanol, Virahol.Add the catalyzer of the ketone of 1 ~ 99 times or aldehyde and 0.1 ~ 50 times afterwards, catalyzer adopts alkali, wherein preferably: sodium hydroxide, potassium hydroxide, sodium alkoxide, potassium alcoholate.Above order of addition(of ingredients) is not fixed.
(2) in conventional heating device, reactant reacts the several seconds to a couple of days, with thin-layer chromatography detection reaction progress at room temperature to stirred at reflux condition.Type of heating comprises external heat and microwave heating.The developping agent that thin-layer chromatography adopts is: ethyl acetate, sherwood oil, methyl alcohol, methylene dichloride, chloroform, acetone, tetrahydrofuran (THF), normal hexane, or is wherein two or three mixed solution.
(3), after reaction terminates, vacuum rotary steam removes most of solvent, is cooled to room temperature, and adding distil water, suction filtration, is washed to neutrality.
(4) recrystallization is carried out to the thick product that step 3 obtains, obtain pure target compound.The solvent of recrystallization can be, but be not limited only to methyl alcohol, ethanol, no isopropanol, ethyl acetate, acetone, acetonitrile, tetrahydrofuran (THF), dioxane, methylene dichloride, chloroform, ethylene dichloride, benzene,toluene,xylene, dimethyl sulfoxide (DMSO), DMF, water, hydrochloric acid, aqueous sulfuric acid, aqueous sodium hydroxide solution.Adopt silicagel column or alumina column during column chromatography, eluent is, but is not limited to ethyl acetate/petroleum ether (1:1 ~ 1:10, volume ratio), methyl alcohol/chloroform (1:1 ~ 1:50, volume ratio), methylene dichloride and acetone.
Further preferably: the condition optimization of step one is: by 3,4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile) join in 5ml ethanolic soln, add the ketone of 3.0 equivalents or the sodium ethylate of aldehyde and 2.0 equivalents afterwards.
The condition optimization of step 2 is: heating condition is solvent refluxing, and thin-layer chromatography adopts methyl alcohol, methylene dichloride is developping agent.
The condition optimization of step 3 is: after reaction terminates, and decompression is outstanding removes most of solvent, is cooled to room temperature, and adding distil water, suction filtration, is washed to neutrality.
The condition optimization of step 4 is: adopt ethanol to step 3 recrystallization solvent, or adopts silicagel column during column chromatography, and eluent, with ethyl acetate/petroleum ether (1:5, volume ratio), obtains pure target compound.
The invention has the advantages that: raw material is cheaply easy to get, technique is simple, reaction conditions is gentle, by product is few, convenient post-treatment, productive rate are better.
(4) accompanying drawing illustrates:
The structural formula figure of Fig. 1 of the present invention pair of Thienopyrimidine ketone compound
The x-ray crystal structure figure of Fig. 2 of the present invention pair of Thienopyrimidine ketone compound
The thermal multigraph of Fig. 3 of the present invention pair of Thienopyrimidinones Compound I
The thermal multigraph of Fig. 4 of the present invention pair of Thienopyrimidine ketone compound II
(5) embodiment:
Embodiment 1
5ml ethanol is added in 25ml single port flask, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) and acetone (3mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate is 74%.
1H NMR(DMSO-d
6,400MHz)δ:7.61(s,2H,NH),7.22(s,2H,NH),1.50(s,12H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:161.0,147.6,143.1,126.2,106.0,69.0,28.0.
Embodiment 2
In 25ml single port flask, add 3ml butanone, add 3,4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) afterwards, be stirred to dispersed, drip sodium methoxide solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product is that eluent carries out purification by silica gel column chromatography with ethyl acetate/petroleum ether (1:5, volume ratio) mixed solution, obtains yellow solid.Productive rate is 61%.
1H NMR(DMSO-d
6,400MHz)δ:7.61(s,2H,NH),7.16(d,J=7.41Hz,2H,NH),1.79(dd,J=7.78,16.07Hz,4H,CH
2),1.47(t,J=13.77Hz,6H,CH
3),0.90(dd,J=7.14,16.51Hz,6H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:160.9,147.4,143.0,142.9,126.2,105.5,105.4,71.7,71.6,32.2,26.4,26.0,8.4,8.3
Embodiment 3
In 25ml single port flask, add 3ml propione, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol), be stirred to dispersed, drip sodium carbonate solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate is 62%.
1H NMR(DMSO-d
6,400MHz)δ:7.62(s,2H,NH),7.11(d,J=12.72Hz,2H,NH),1.70(d,J=38.01Hz,4H,CH
2),1.47(d,J=4.05Hz,6H,CH
3),1.40(s,4H,CH
2),0.87(d,J=6.14Hz,6H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:160.9,147.4,143.0,142.9,126.1,105.6,71.4,71.3,42.1,26.8,26.5,16.8,14.0.
Embodiment 4
In 25ml single port flask, add 3ml propione, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol), be stirred to dispersed, drip sodium hydroxide solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate is 60%.
1H NMR(DMSO-d
6,400MHz)δ:7.51(s,2H,NH),6.97(s,2H,NH),1.78(dd,J=13.63,7.01Hz,4H,CH
2),1.68(dd,J=13.21,6.86Hz,4H,CH
2),0.91(d,12H,J=6.34Hz,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:161.1,147.2,143.1,126.1,104.7,74.5,30.8,8.2.
Embodiment 5
In 25ml single port flask, add 3ml 3-methyl-2-butanone, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate is 56%.
1H NMR(DMSO-d
6,400MHz)δ:7.76(s,2H,NH),7.24(s,2H,NH),2.31~2.22(m,2H,CH),1.39(s,6H,CH
3),0.95~0.85(m,12H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:160.3,147.2,142.2,126.1,105.9,73.5,34.2,21.0,17.0,16.3.
Embodiment 6
In 25ml single port flask, add 3ml 4-methyl-2 pentanone, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product tetrahydrofuran (THF) recrystallization obtains yellow solid.Productive rate 66%.
1H NMR(DMSO-d
6,400MHz)δ:7.55(s,2H,NH),7.13,(s,2H,NH)1.83-1.71(m,4H,CH
2),1.50(s,6H,CH
3),0.91-0.84(m,14H,CH(CH
3)
2).
13C NMR(DMSO-d
6,100MHz)δ:160.8,147.3,142.8,126.1,105.3,71.5,47.7,27.0,24.2,23.5.
Embodiment 7
In 25ml single port flask, add 3ml methyl phenyl ketone, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product re-crystallizing in ethyl acetate obtains yellow solid.Productive rate 76%.
1H NMR(DMSO-d6,400MHz)δ:8.63(s,2H,NH),8.31(s,2H,NH),7.58-7.27(m,10H,ArH),1.81(s,6H,CH
3).
13C NMR(DMSO-d6,100MHz)δ:161.4,147.5,147.2,142.8,128.0,127.5,126.0,124.8,108.6,71.9,30.1.
Embodiment 8
In 25ml single port flask, add 3ml Propiophenone, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product DMF recrystallization obtains yellow solid.Productive rate 71%.
1H NMR(DMSO-d
6,400MHz)δ:8.50(s,2H,NH),8.07(s,2H,NH),7.57-7.28(m,10H,ArH)1.97(d,J=33.01,4H,CH
2),1.12(s,6H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:161.7,150.4,147.3,143.1,128.0,127.5,126.4,125.0,108.0,75.3,34.5,9.4
Embodiment 9
5ml acetonitrile is added in 25ml single port flask, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) and pimelinketone (3mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product recrystallizing methanol obtains yellow solid.Productive rate 68%.
1H NMR(DMSO-d
6,400MHz)δ:7.66(s,2H,NH),6.90(s,2H,NH),1.95~1.26(m,20H,CH
2).
13C NMR(DMSO-d
6,100MHz)δ:161.0,147.4,142.5,127.7,108.3,69.3,35.7,24.8,21.5.
Embodiment 10
5ml ethanol is added in 25ml single port flask, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) and cyclopentanone (3mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate 62%.
1H NMR(DMSO-d
6,400MHz)δ:7.84(s,2H,NH),7.27(s,2H,NH),1.93~1.68(m,16H,CH
2).
13C NMR(DMSO-d
6,100MHz)δ:161.4,147.7,143.7,126.3,107.3,78.7,38.3,22.0.
Embodiment 11
5ml ethanol is added in 25ml single port flask, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene 2,5-dintrile (1mmol) and suberone (3mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate 64%.
1H NMR(DMSO-d
6,400MHz)δ:7.75(s,2H,NH),7.12(s,2H,NH),2.03~1.91(m,8H,CH
2),1.53(s,16H,CH
2).
13C NMR(DMSO-d
6,100MHz)δ:160.7,147.3,142.4,126.9,107.2,73.8,39.1,28.7,21.1
Embodiment 12
3ml toluene is added in hydrothermal reaction kettle, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) and methylcyclohexanone (3mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then at 150 DEG C of reaction 3h.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate 50%.
1H NMR(DMSO-d
6,400MHz)δ:7.64(s,2H,NH),7.03(d,J=9.18Hz,2H,NH),2.23~1.42(m,18H,CH
2),0.91~0.86(m,6H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:160.8,147.8,143.0,126.1,106.4,70.7,70.0,44.6,35.7,33.7,31.2,28.9,26.7,22.1,21.5,20.3.
Embodiment 13
In 25ml single port flask, add 3ml butyraldehyde-n, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then rapid temperature increases is to backflow.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.Productive rate 69%.
1H NMR(DMSO-d
6,400MHz)δ:7.64(s,2H,NH),7.17(s,2H,NH),4.79(s,2H,CH),1.74(s,4H,CH
2),1.47(s,4H,CH
2),0.93(d,J=6.96Hz,6H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:162.1,148.1,144.8,126.1,108.3,65.7,35.4,17.1,13.8.
Embodiment 14
In mortar, add 5ml methylene dichloride, add 3,4-diaminothiophen also [2 afterwards, 3-b] thiophene-2,5-dintrile (1mmol) and 2-naphthaldehyde (3mmol), drip alcohol sodium solution (2mmol), then grind 30min.Thin-layer chromatography detects, and after reaction terminates, vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.
1H NMR(DMSO-d
6,400MHz)δ:13.13(s,2H,NH),8.39-7.37(m,14H,ArH).
13CNMR(DMSO-d
6,100MHz)δ:160.0,152.3,149.3,144.3,136.0,135.2,133.9,130.3,128.2,128.1,126.2,124.1,123.8,123.0.HRMS(ESI
+)m/z calcd for(C
30H
17N
4O
2S
2)
+,529.07874;found 529.07700.
Embodiment 15
2ml ethanol is added in microwave tube, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) and 2-oxyethyl group formaldehyde (3mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then microwave heating 10min.Vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product methyl alcohol/chloroform (1:50, volume ratio) obtains yellow solid.
1H NMR(DMSO-d
6,400MHz)δ:12.53(s,2H,NH),7.80-7.09(m,8H,ArH),4.19-4.14(m,4H,CH
2),1.35-1.32(m,6H,CH
3);
13C NMR(DMSO-d
6,100MHz)δ:160.0,159.2,154.1,149.3,144.3,136.0,130.7,124.7,123.0,120.4,114.5,106.3,64.6,14.8.HRMS(ESI
+)m/z calcd for(C
26H
21N
4O
4S
2)
+,517.09987;found529.09935.
Embodiment 16
5ml ethanol is added in 25ml single port flask, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) and 2-oxyethyl group formaldehyde (3mmol), be stirred to dispersed, drip alcohol sodium solution (2mmol), then microwave heating 10min.Vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product ethyl alcohol recrystallization obtains yellow solid.
1H NMR(DMSO-d
6,400MHz)δ:12.98(s,2H,NH),8.32-7.47(m,8H,ArH),2.77-2.71(m,4H,CH
2),1.28-1.24(m,6H,CH
3).
13C NMR(DMSO-d
6,100MHz)δ:160.0,152.3,149.3,145.7,144.3,136.0,130.3,129.6,127.8,123.0,28.2,14.5.HRMS(ESI
+)m/z calcd for(C
26H
21N
4O
2S
2)
+,485.11004;found 485.10922.
Embodiment 17
5ml ethanol is added in 25ml single port flask, add 3 afterwards, 4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile (1mmol) and 3-thiophenecarboxaldehyde (3mmol), be stirred to dispersed, drip potassium hydroxide solution (2mmol), then microwave heating 30min.Vacuum rotary steam removes most of solvent, is chilled to room temperature.Add distilled water, suction filtration, be washed to neutrality.Crude product Gossypol recrystallized from chloroform obtains yellow solid.
1H NMR(DMSO-d
6,400MHz)δ:11.40(s,2H,NH),7.67(s,2H,ArH),7.32(m,4H,ArH).
13C NMR(DMSO-d
6,100MHz)δ:160.0,159.3,143.3,144.7,136.0,127.6,126.8,125.6,124.2,123.0.
Claims (7)
1. a method for the two Thienopyrimidine ketone derivatives of synthesis, is characterized in that: with 3,4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile and ketone or aldehyde reaction synthesize pair Thienopyrimidine ketone derivatives, reaction expression is:
Wherein R
1and R
2for hydrogen; Fatty compounds, is selected from the C of straight chain, side chain or ring-type
1-6alkyl, alkenyl or alkynyl; Aromatics is phenyl ring or heterocycle structure, comprises containing substituent aromatic nucleus, is selected from benzene, naphthalene, anthracene, thiophene, pyridine, furans, pyrroles, pyrazoles, imidazoles, thiazole, thionaphthene, indoles, benzoglyoxaline, benzoxazoles or benzothiazole etc.; This substituent quantity and position are not limit.
2. a kind of method of synthesizing two Thienopyrimidine ketone derivatives as claimed in claim 1, is characterized in that: the catalyzer of this reaction is basic catalyst, includes but not limited to sodium carbonate, sodium hydroxide, potassium hydroxide, sodium alkoxide, potassium alcoholate; Synthesis device is the one in constant-temperature magnetic stirring device, Microwave synthesize instrument, hydrothermal reaction kettle and mortar solid phase synthetic instrument.
3. a kind of method of synthesizing two Thienopyrimidine ketone derivatives as claimed in claim 1, is characterized in that:
1) wherein alkyl is selected from the C of straight or branched
1-6alkyl, alkoxyl group is selected from the C of straight or branched
1-6alkoxyl group, aryl is selected from C
6-10aryl, heteroaryl is selected from 5 to the 10 yuan of heteroaryls comprising 1 to 3 Sauerstoffatom, nitrogen-atoms or sulphur atom;
2) wherein alkyl is selected from methyl, ethyl, propyl group, butyl, amyl group and hexyl; Alkoxyl group is selected from methoxyl group, oxyethyl group, propoxy-, butoxy, pentyloxy and hexyloxy;
3) aryl is selected from benzene, naphthalene, anthracene; Heteroaryl is selected from pyridine, pyrimidine, thiophene, furans, pyrroles and pyrans.
4. a kind of method of synthesizing two Thienopyrimidine ketone derivatives as claimed in claim 1, it is characterized in that: reaction medium is water, methyl alcohol, ethanol, acetonitrile, methylene dichloride, hexanaphthene, toluene, N, dinethylformamide, N, N-diethylformamide, tetrahydrofuran (THF), aldehyde, ketone, toluene, dimethyl sulfoxide (DMSO), dioxane, halogenated alkane, Virahol etc., or be wherein two or more mixed solution.
5. a kind of method of synthesizing two Thienopyrimidine ketone derivatives as claimed in claim 1, is characterized in that:
1) ratio of reactant 3, the 4-diaminothiophen also amount of substance of [2,3-b] thiophene-2,5-dintrile and ketone or aldehyde is 1:1 ~ 1:99;
2) reactant 3,4-diaminothiophen also [2,3-b] thiophene-2,5-dintrile be 1:0.1 ~ 1:50 with the ratio of the amount of substance of catalyzer;
3) at 150 DEG C, 0.01h-100.0h is reacted at 25 DEG C.
6. a kind of method of synthesizing two Thienopyrimidine ketone derivatives as claimed in claim 1, is characterized in that: reaction is terminated the most of reaction solvent of rear removing, add water, suction filtration, obtains crude product.
7. a kind of method of synthesizing two Thienopyrimidine ketone derivatives as claimed in claim 1, is characterized in that: carry out recrystallization or column chromatography purification for crude product, obtains the pure target compound that productive rate is 1-99%.Recrystallization solvent can be, but be not limited to methyl alcohol, ethanol, Virahol, ethyl acetate, acetone, acetonitrile, tetrahydrofuran (THF), dioxane, methylene dichloride, chloroform, ethylene dichloride, benzene,toluene,xylene, dimethyl sulfoxide (DMSO), DMF, hydrochloric acid, aqueous sulfuric acid, aqueous sodium hydroxide solution.Adopt silicagel column or alumina column during column chromatography, eluent is, but is not limited to ethyl acetate/petroleum ether (1:1 ~ 1:10, volume ratio), methyl alcohol/chloroform (1:1 ~ 1:50, volume ratio), methylene dichloride and acetone.
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