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CN102276616A - Method for synthesizing furan[3,2-c] pyridine-4(5H) ketone compound - Google Patents

Method for synthesizing furan[3,2-c] pyridine-4(5H) ketone compound Download PDF

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CN102276616A
CN102276616A CN2011102215729A CN201110221572A CN102276616A CN 102276616 A CN102276616 A CN 102276616A CN 2011102215729 A CN2011102215729 A CN 2011102215729A CN 201110221572 A CN201110221572 A CN 201110221572A CN 102276616 A CN102276616 A CN 102276616A
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dimethylin
propionic acid
acid amide
acryl
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CN102276616B (en
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董德文
黄鹏
梁永久
张睿
张定远
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Changzhou Institute Of Energy Storage Materials & Devices
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Changchun Institute of Applied Chemistry of CAS
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Abstract

一种呋喃[3，2-c]吡啶-4(5H)-酮类化合物合成方法，属于有机合成技术领域。现有合成方法合成步骤繁杂，反应条件苛刻，原料不易得，合成成本高，产率低，所获得的产物取代基和官能团少。本发明之方法其特征在于，第一步：在室温下将N，N-二甲基甲酰胺(DMF)和三氟甲磺酸酐(Tf2O)按(10～150)∶1摩尔比混合，搅拌2～10分钟；第二步：加入环丙酰胺类化合物，加入量为三氟甲磺酸酐加入量的0.3～1.0摩尔倍数，升温至70～120℃，搅拌0.2～3.0小时，生成最终产物呋喃[3，2-c]吡啶-4(5H)-酮类化合物，该产物取代基和官能团多，适合作为中间体参与进一步的有机合成反应；合成成本大幅降低；同时产率大幅提高。A method for synthesizing furo[3,2-c]pyridin-4(5H)-one compounds belongs to the technical field of organic synthesis. The existing synthesis method has complex synthesis steps, harsh reaction conditions, difficult to obtain raw materials, high synthesis cost, low yield, and the obtained product has few substituents and functional groups. The method of the present invention is characterized in that the first step: mix N,N-dimethylformamide (DMF) and trifluoromethanesulfonic anhydride (Tf 2 O) at room temperature in a molar ratio of (10-150): 1 , stirring for 2 to 10 minutes; the second step: adding cyclopropanamide compounds in an amount of 0.3 to 1.0 mole multiples of the amount of trifluoromethanesulfonic anhydride, raising the temperature to 70 to 120°C, and stirring for 0.2 to 3.0 hours to form the final The product furo[3,2-c]pyridin-4(5H)-one compound has many substituents and functional groups, and is suitable as an intermediate to participate in further organic synthesis reactions; the synthesis cost is greatly reduced; and the yield is greatly increased.

Description

A kind of furans [3,2-c] pyridines-4 (5H)-ketone compounds synthetic method
Technical field
The present invention relates to a kind of furans [3; 2-c] pyridine-4 (5H)-ketone compounds synthetic method; by N-replacement-1-(3-(dimethylin) acryl)-ring Propionamides compound; synthetic furans [3 under trifluoromethanesulfanhydride anhydride/DMF reaction conditions; 2-c] pyridine-4 (5H)-ketone compounds, belong to technical field of organic synthesis.
Background technology
Furans [3,2-c] pyridines-4 (5H)-ketone compounds belongs to a kind of furo pyridine compounds, extensively is present in the natural product, has important biology and pharmaceutical activity (1. Acta Chem.Scand.1998,52,631～634; 2. J.Antibiot.2002,55,6～18).
The synthetic method of this compounds mainly contains two classes in the prior art: a class be on the basis of existing furan nucleus through multistep tradition organic chemical reactions make up the pyridone ring (J.Med.Chem.1989,32,1147-1156).Though the employed raw material of this method also can suitability for industrialized production,, do not become bulk product, so price is higher; This method expects that from former final product needs four steps at least, and on average each step productive rate is 80%, and synthetic overall yield only is about 40%; This method severe reaction conditions also need be taked antifouling, measures for the prevention of explosion in building-up process, therefore synthetic cost improves.Another kind of is to make up furan nucleus (1. J.Org.Chem.2008,73,8619-8622 through intramolecular heterocyclization on the basis of existing pyridone ring; 2. Synthesis, 2010,1741-1744), its shortcoming is that raw material is not easy to obtain, and the catalyzer costliness.
In addition, adopt existing two class synthetic method synthetic product furans [3,2-c] pyridines-4 (5H)-ketone compounds substituting groups and functional group few, limited such product and participated in further organic synthesis as intermediate.
Summary of the invention
Its purpose of the present invention is, simplify furans [3,2-c] synthesis step of pyridine-4 (5H)-ketone compounds, make reaction conditions gentleness, raw material be easy to get, reduce synthetic cost, improve productive rate, the product that is obtained has more substituting group and functional group, for this reason, a kind of furans [3,2-c] pyridines-4 (5H)-ketone compounds synthetic method is proposed.
The present invention's method is characterized in that,
The first step: at room temperature with N, dinethylformamide (DMF) and trifluoromethanesulfanhydride anhydride (Tf 2O) by (10～150): 1 mixed in molar ratio, stirred 2～10 minutes;
Second step: add the ring Propionamides compound, add-on is 0.3～1.0 mole of multiple of trifluoromethanesulfanhydride anhydride add-on, is warming up to 70～120 ℃, stirs 0.2～3.0 hour;
Reaction formula is as follows:
Its effect of the present invention is, building-up process has only two steps, rapid and the N of reactant trifluoromethanesulfanhydride anhydride in the first step, the dinethylformamide reaction generates an intermediate, and intermediate and the reaction of reaction raw materials ring Propionamides compound N-take place replace in second step, make up furan nucleus and pyridone ring simultaneously, generate product furans [3,2-c] pyridines-4 (5H)-ketone compounds, its structural formula is as follows:
Learn that by this specification sheets embodiment partial content adopt furans [3,2-c] pyridines-4 (the 5H)-ketone compounds of the present invention's method institute gained, its degree of unsaturation height, substituting group and functional group are many, and contain functional groups such as aldehyde radical or acyl group.Building-up process is carried out under normal pressure and lesser temps, the reaction conditions temperature, and step is simple, and raw material is easy to get, and without catalyzer, thereby synthetic cost significantly reduces; Productive rate significantly improves simultaneously, reaches as high as 95% as productive rate.
Embodiment
The first step: at room temperature add solvent N in the reactor that agitator is housed, dinethylformamide (DMF) under agitation slowly adds trifluoromethanesulfanhydride anhydride (Tf then in solvent 2O), institute adds N, and the mol ratio of dinethylformamide and trifluoromethanesulfanhydride anhydride is (10～150): 1, afterwards mixed solution is continued to stir 2～10 minutes;
Second step: add reaction raw materials ring Propionamides compound in described mixed solution, form reaction solution, described ring Propionamides compound is one of following compounds:
1-(3-(dimethylin) acryl)-N-p-methylphenyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-N-benzyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-2-phenyl-N-p-methylphenyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-N-o-tolyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-N-(2, the 4-3,5-dimethylphenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(4-p-methoxy-phenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(2-p-methoxy-phenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(2-chloro-phenyl-) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(4-(trifluoromethyl) phenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-benzyl rings propionic acid amide,
1-(3-(dimethylin) but-2-ene acyl group)-N-benzyl ring propionic acid amide,
N-(4-chloro-phenyl-)-1-(3-(dimethylin) enoyl-) encircles propionic acid amide,
Because of the difference of ring Propionamides compound kind, the R of synthetic product 1, R 2, R 3Also different, add-on is warming up to 70～120 ℃ for 0.3～1.0 mole of multiple of add trifluoromethanesulfanhydride anhydride, stirs 0.2～3.0 hour, generates final product;
Reaction formula is as follows:
Figure BDA0000080987530000031
Described reaction solution is poured in the saturated aqueous common salt, with organic solvent such as dichloromethane extraction, washing and with siccative such as anhydrous magnesium sulfate drying organic phase, remove by filter siccative, steam and remove organic solvent, separate, obtain product furans [3 through silica gel column chromatography, 2-c] pyridine-4 (5H)-ketone compounds, its structural formula is as follows:
Figure BDA0000080987530000032
In the formula:
R 1For-H ,-CH 3,-CH 2CH 3,-(CH 2) 2CH 3,-CH (CH 3) 2,-(CH 2) 3CH 3,-CH 2CH (CH 3) 2,-C (CH 3) 3,-(CH 2) 4CH 3,-CH 2C (CH 3) 3,-(CH 2) 5CH 3, (CH 2) 5CH-, CH 2=CH-, CH 2=CHCH 2-, PhCH 2-, Ph-, 4-CH 3OC 6H 4CH 2-, 4-(CH 3CH 2) C 6H 4-, 4-[(CH 3) 2N] C 6H 4-, 4-[CH (CH 3) 2] C 6H 4-, 4-CH 3OC 6H 4-, 4-(CH 3CH 2O) C 6H 4-, 4-[(CH 3CH 2) 2N] C 6H 4-, 4-ClC 6H 4-, 4-BrC 6H 4-, 4-FC 6H 4-, 4-IC 6H 4-, 4-CF 3C 6H 4-, 4-NO 2C 6H 4-, 4-CNC 6H 4-, 2-CH 3C 6H 4-, 2-(CH 3CH 2) C 6H 4-, 2-[(CH 3) 2N] C 6H 4-, 2-CH 3OC 6H 4-, 2-(CH 3CH 2O) C 6H 4-, 2-[(CH 3CH 2) 2N] C 6H 4-, 2-CF 3C 6H 4-, 2-ClC 6H 4-, 2-BrC 6H 4-, 2-FC 6H 4-, 2-IC 6H 4-, 2-NO 2C 6H 4-, 2-CNC 6H 4-, 3-CH 3C 6H 4-, 3-(CH 3CH 2) C 6H 4-, 3-(CH 3CH 2O) C 6H 4-, 3-CH 3OC 6H 4-, 3-ClC 6H 4-, 3-BrC 6H 4-, 3-FC 6H 4-, 3-IC 6H 4-, 3-NO 2C 6H 4-, 3-CNC 6H 4-, 2,4-(CH 3) 2C 6H 3-, 3,4-(CH 3) 2C 6H 3-, 3,5-(CH 3) 2C 6H 3-, 2,4-(CH 3O) C 6H 4-, 2-CH 3O-4-ClC 6H 3-or 4-CH 3C 6H 4SO 2-;
R 2For-H ,-CH 3,-CH 2CH 3,-(CH 2) 2CH 3,-CH (CH 3) 2,-(CH 2) 3CH 3,-CH 2CH (CH 3) 2,-C (CH 3) 3,-(CH 2) 4CH 3,-CH=CH 2, CH 2=CHCH 2-, PhCH 2-, Ph-, 4-CH 3OC 6H 4CH 2-, 4-CH 3C 6H 4-, 4-[(CH 3) 2N] C 6H 4-, 4-CH 3OC 6H 4-, 4-[(CH 3CH 2) 2N] C 6H 4-, 4-ClC 6H 4-, 4-BrC 6H 4-, 4-FC 6H 4-, 4-IC 6H 4-, 4-CF 3C 6H 4-, 2-CH 3C 6H 4-, 2-CF 3C 6H 4-, 2-CH 3OC 6H 4-, 2-ClC 6H 4-, 2-BrC 6H 4-, 2-FC 6H 4-, 2-IC 6H 4-, 3-CH 3C 6H 4-, 3-CH 3OC 6H 4-, 3-ClC 6H 4-, 3-BrC 6H 4-, 3-FC 6H 4-, 3-IC 6H 4-, 2,4-(CH 3) 2C 6H 3-or 2,4-(CH 3O) C 6H 4-;
R 3For-H ,-CH 3,-CH 2CH 3,-(CH 2) 2CH 3,-CH (CH 3) 2,-(CH 2) 3CH 3,-CH 2CH (CH 3) 2,-C (CH 3) 3,-(CH 2) 4CH 3,-CH 2C (CH 3) 3, CH 2=CHCH 2-, PhCH 2-,-Ph, 4-CH 3OC 6H 4CH 2-, 4-CH 3OC 6H 4-, 4-[(CH 3) 2N] C 6H 4-, 4-(CH 3CH 2O) C 6H 4-, 4-[(CH 3CH 2) 2N] C 6H 4-, 4-ClC 6H 4-, 4-BrC 6H 4-, 4-FC 6H 4-, 4-IC 6H 4-, 4-CF 3C 6H 4-, 2-CH 3C 6H 4-, 2-(CH 3CH 2) C 6H 4-, 2-CH 3OC 6H 4-, 2-ClC 6H 4-, 2-BrC 6H 4-, 2-FC 6H 4-, 2-IC 6H 4-, 3-CH 3C 6H 4-, 3-CH 3OC 6H 4-, 3-ClC 6H 4-, 3-BrC 6H 4-, 3-FC 6H 4-, 3-IC 6H 4-, 2,4-(CH 3) 2C 6H 3-or 2,4-(CH 3O) C 6H 4-.
Illustrate the present invention's method below.
Embodiment 1:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 10.0 milliliters of DMF, stir, in 5 minutes to wherein dripping 3.0 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 3 minutes.In mixed solution, add 1-(3-(dimethylin) the acryl)-N-p-methylphenyl ring propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 100 ℃ then, stirred 2.5 hours, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 88%.Reaction formula is as follows:
Figure BDA0000080987530000041
The data characterization of product furans [3,2-c] pyridines-4 (5H)-ketone:
White solid, fusing point are 188～189 ℃.
Proton nmr spectra (300MHz, CDCl 3): δ=2.42 (s, 3H), 3.16 (t, J=9.3,2H), 4.86 (t, J=9.3,2H), 7.23 (d, J=8.1,2H), 7.30 (d, J=8.1,2H), 8.00 (s, 1H), 9.79 (s, 1H).
Carbon-13 nmr spectra (150MHz, CDCl 3): δ=211,26.5,74.6,108.7,109.3,126.3,130.0,137.0,139.2,145.8,160.2,166.1,184.6.
Ultimate analysis theoretical value: C, 70.58; H, 5.13; N, 5.49. measured value: C, 70.43; H, 5.17; N, 5.58.
Mass spectrum theoretical value m/z 255.1, measured value: 256.1[(M+1) +].
Embodiment 2:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 8.0 milliliters of DMF, stir, in 5 minutes to wherein dripping 1.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 7 minutes.In mixed solution, add 1-(3-(dimethylin) the acryl)-N-benzyl ring propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 85 ℃ then, stirred 3.0 hours, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H0-ketone, productive rate 95%.Reaction formula is as follows:
Figure BDA0000080987530000051
Embodiment 3:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 5.0 milliliters of DMF, stir, in 4 minutes to wherein dripping 2.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 2 minutes.In mixed solution, add 1-(3-(dimethylin) the acryl)-N-benzyl ring propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 70 ℃ then, stirred 2.0 hours, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 91%.Reaction formula is as follows:
Figure BDA0000080987530000052
Embodiment 3 is identical with the reaction raw materials ring Propionamides compound that embodiment 2 is added, but reaction conditions is variant, so the productive rate difference.
Embodiment 4:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 2.0 milliliters of DMF, stir, in 2 minutes to wherein dripping 1.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 5 minutes.In mixed solution, add 1-(3-(dimethylin) the acryl)-2-phenyl-N-p-methylphenyl ring propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 90 ℃ then, stirred 1.5 hours, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 82%.Reaction formula is as follows:
Figure BDA0000080987530000061
Embodiment 5:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 7.0 milliliters of DMF, stir, in 3 minutes to wherein dripping 1.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 5 minutes.In mixed solution, add 1-(3-(dimethylin) the acryl)-N-o-tolyl ring propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 100 ℃ then, stirred 2.0 hours, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 87%.Reaction formula is as follows:
Figure BDA0000080987530000062
Embodiment 6:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 7.0 milliliters of DMF, stir, in 4 minutes to wherein dripping 2.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 4 minutes.1-(3-(dimethylin) the acryl)-N-(2, the 4-3,5-dimethylphenyl) that adds 1.0 mmoles in mixed solution encircles propionic acid amide afterwards, forms reaction solution, is warming up to 100 ℃ then, stirs 1.0 hours, stops building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 85%.Reaction formula is as follows:
Figure BDA0000080987530000071
Embodiment 7:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 3.0 milliliters of DMF, stir, in 1 minute to wherein dripping 1.0 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 2 minutes.1-(3-(dimethylin) the acryl)-N-(4-p-methoxy-phenyl) that adds 1.0 mmoles in mixed solution encircles propionic acid amide afterwards, forms reaction solution, is warming up to 100 ℃ then, stirs 2.0 hours, stops building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 66%.Reaction formula is as follows:
Embodiment 8:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 5.0 milliliters of DMF, stir, in 3 minutes to wherein dripping 2.0 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 2 minutes.1-(3-(dimethylin) the acryl)-N-(2-p-methoxy-phenyl) that adds 1.0 mmoles in mixed solution encircles propionic acid amide afterwards, forms reaction solution, is warming up to 100 ℃ then, stirs 2.0 hours, stops building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 89%.Reaction formula is as follows:
Figure BDA0000080987530000081
Embodiment 9:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 5.0 milliliters of DMF, stir, in 3 minutes to wherein dripping 2.0 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 2 minutes.1-(3-(dimethylin) the acryl)-N-(2-chloro-phenyl-) that adds 1.0 mmoles in mixed solution encircles propionic acid amide afterwards, forms reaction solution, is warming up to 100 ℃ then, stirs 2.0 hours, stops building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 82%.Reaction formula is as follows:
Embodiment 10:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 5.0 milliliters of DMF, stir, in 4 minutes to wherein dripping 2.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 4 minutes.1-(3-(dimethylin) the acryl)-N-(4-(trifluoromethyl) phenyl) that adds 1.0 mmoles in mixed solution encircles propionic acid amide afterwards, forms reaction solution, is warming up to 100 ℃ then, stirs 3.0 hours, stops building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 89%.Reaction formula is as follows:
Figure BDA0000080987530000091
Embodiment 11:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 5.0 milliliters of DMF, stir, in 4 minutes to wherein dripping 2.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 4 minutes.In mixed solution, add 1-(3-(dimethylin) the acryl)-N-benzyl rings propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 90 ℃ then, stirred 0.5 hour, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 84%.Reaction formula is as follows:
Figure BDA0000080987530000092
Embodiment 12:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 5.0 milliliters of DMF, stir, in 4 minutes to wherein dripping 2.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 4 minutes.In mixed solution, add 1-(3-(dimethylin) but-2-ene the acyl group)-N-benzyl ring propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 110 ℃ then, stirred 1.5 hours, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 80%.Reaction formula is as follows:
Embodiment 13:
At room temperature, in 25 milliliters of round-bottomed flask reactors that agitator is housed, add 2.0 milliliters of DMF, stir, in 4 minutes to wherein dripping 2.5 mmole Tf 2O forms DMF and Tf 2The O mixed solution stirred 10 minutes.In mixed solution, add N-(4-chloro-phenyl-)-1-(3-(dimethylin) enoyl-) ring propionic acid amide of 1.0 mmoles afterwards, form reaction solution, be warming up to 120 ℃ then, stirred 0.25 hour, stop building-up process.Reaction solution is poured in 200 milliliters of saturated aqueous common salts, divide three extractions with 60 milliliters of methylene dichloride, merge organic phase, respectively with 30 milliliters of washings twice, with 10 gram anhydrous magnesium sulfate dryings, remove by filter sal epsom, steam and remove organic solvent, residuum separates through silica gel column chromatography, obtains product furans [3,2-c] pyridine-4 (5H)-ketone, productive rate 92%.Reaction formula is as follows:
Figure BDA0000080987530000101

Claims (2)

1. furans [3,2-c] pyridines-4 (5H)-ketone compounds synthetic method is characterized in that:
The first step: at room temperature with N, dinethylformamide (DMF) and trifluoromethanesulfanhydride anhydride (Tf 2O) by (10～150): 1 mixed in molar ratio, stirred 2～10 minutes;
Second step: add the ring Propionamides compound, add-on is 0.3～1.0 mole of multiple of trifluoromethanesulfanhydride anhydride add-on, is warming up to 70～120 ℃, stirs 0.2～3.0 hour;
Reaction formula is as follows:
Figure FDA0000080987520000011
2. furans according to claim 1 [3,2-c] pyridines-4 (5H)-ketone compounds synthetic method is characterized in that, described ring Propionamides compound is one of following compounds:
1-(3-(dimethylin) acryl)-N-p-methylphenyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-N-benzyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-2-phenyl-N-p-methylphenyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-N-o-tolyl ring propionic acid amide,
1-(3-(dimethylin) acryl)-N-(2, the 4-3,5-dimethylphenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(4-p-methoxy-phenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(2-p-methoxy-phenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(2-chloro-phenyl-) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-(4-(trifluoromethyl) phenyl) encircles propionic acid amide,
1-(3-(dimethylin) acryl)-N-benzyl rings propionic acid amide,
1-(3-(dimethylin) but-2-ene acyl group)-N-benzyl ring propionic acid amide,
N-(4-chloro-phenyl-)-1-(3-(dimethylin) enoyl-) encircles propionic acid amide.
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