CN110256423B - Method for preparing 3-dibromo methyl imidazo [1, 2-alpha ] pyridine derivative - Google Patents
Method for preparing 3-dibromo methyl imidazo [1, 2-alpha ] pyridine derivative Download PDFInfo
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Abstract
The invention provides a method for preparing 3-dibromo methyl imidazo [1, 2-alpha ]]A process for preparing a pyridine derivative, comprising: adding R into a reaction vessel1、R2、R3Substituted N- (2-pyridyl) amidines, CBr4Reacting the mixture with an organic solvent and a catalyst for 8 to 16 hours at the temperature of 100 ℃ and 120 ℃ under the protection of nitrogen, filtering, concentrating and separating by column chromatography after the reaction is finished to obtain the 3-dibromomethyl imidazo [1, 2-alpha ]]A pyridine derivative.
Description
Technical Field
The invention belongs to the field of organic chemistry, and particularly relates to a method for preparing a 3-dibromo methyl imidazo [1, 2-alpha ] pyridine derivative.
Background
Imidazo [1,2- α ] pyridines and derivatives thereof are a class of substances with specific structural motifs that are used in a wide variety of compounds due to their broad pharmaceutical and biological properties, in particular the potent anticancer and antiviral activities highlighted by imidazo [1,2- α ] pyridines, such as antibacterial, antiviral, antitubercular, antitumoral, thus imidazo [1,2- α ] pyridines can be said to be valuable cornerstones in drug discovery. In addition, imidazo [1,2- α ] pyridine derivatives have wide applications in organic synthesis and material science. At present, the method for synthesizing imidazo [1,2-a ] pyridine is mainly prepared by alpha-halogenated acetophenone and 2-aminopyridine through cyclization condensation reaction, but the existing method still has the defects of high cost, harsh reaction conditions, low yield and the like. Therefore, the practical method for synthesizing the imidazo [1, 2-alpha ] pyridine derivatives has great significance for medicine and biomedical research.
Disclosure of Invention
The invention aims to provide a preparation method of a 3-dibromo-methyl imidazo [1, 2-alpha ] pyridine derivative, which has a simple preparation process and high yield.
In order to achieve the above object, the present invention provides a method for preparing 3-dibromomethyl imidazo [1, 2-alpha ]]A process for preparing a pyridine derivative, comprising: adding R into a reaction vessel1、R2、R3Substituted N- (2-pyridyl) amidines, CBr4Reacting the mixture with an organic solvent and a catalyst for 8 to 16 hours at the temperature of 100 ℃ and 120 ℃ under the protection of nitrogen, filtering, concentrating and separating by column chromatography after the reaction is finished to obtain the 3-dibromomethyl imidazo [1, 2-alpha ]]Pyridine derivatives (i.e. R)1、R2、R3Substituted 3-dibromomethylimidazo [1, 2-alpha ]]Pyridine).
Preferably, R is1Is at least one of an electron donating group and an electron withdrawing group.
More preferably, the electron donating group is at least one of H, methyl and chlorine, R2Is at least one of phenyl, 4-ethylphenyl, 4-methoxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3-fluorophenyl, 4-fluorophenyl and n-butyl; r3Is at least one of 4-methylbenzene, phenyl and methyl.
Preferably, the catalyst is at least one of potassium carbonate, cesium carbonate, triethylamine, DBU, potassium tert-butoxide and lithium tert-butoxide.
Preferably, R is1、R2、R3Substituted N- (2-pyridyl) amidines, CBr4The amount of catalyst, calculated in terms of molar ratio, R1、R2、R3Substituted N- (2-pyridyl) amidines, CBr4And the catalyst is 1-1.2: 1-1.2: 2 to 2.4.
Preferably, the organic solvent is used in an amount, as R1、R2、R3Substituted N- (2-pyridyl) amidines: organic solvent 0.2 mmol: the ratio of 1.5-2ml is calculated.
Preferably, the organic solvent is dichloromethane, tetrahydrofuran, acetonitrile, more preferably dichloromethane.
Preferably, the catalyst is at least one of potassium carbonate, cesium carbonate, triethylamine, DBU, potassium tert-butoxide and lithium tert-butoxide, more preferably potassium carbonate.
The reaction equation of the preparation process of the present invention is as follows:
compared with the prior art, the invention has the beneficial effects that:
the preparation method of the 3-dibromo-methyl imidazo [1, 2-alpha ] pyridine has the advantages of high reaction efficiency, high product yield, simple post-treatment and good industrial application prospect, and the initial raw materials are easy to obtain, cheap and have wide characteristics and simple reaction conditions, and are easy to separate.
Drawings
FIG. 1 is a single crystal spectrum of (Z) -N- (3- (dibromomethyl) -3-phenylimidazo [1,2-a ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide obtained in example 1.
FIG. 2 is a NMR spectrum of (Z) -N- (3- (dibromomethyl) -3-phenylimidazo [1,2-a ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide obtained in example 1.
FIG. 3 is a NMR carbon spectrum of (Z) -N- (3- (dibromomethyl) -3-phenylimidazo [1,2-a ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide obtained in example 1.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.
Example 1
A10 ml reaction flask was charged with 41mg of potassium carbonate, 73mg of 4-methyl-N- [ 2-phenyl-1- (pyridin-2-ylamino) -ethylidene ] -benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was replaced three times; stirring the reaction mixture at 100 ℃ for 12h under the protection of nitrogen, tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (3- (dibromomethyl) -3-phenylimidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide with a yield of 78%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.42(d,J=6.4Hz,1H),8.02(t,J=7.6Hz,1H),7.85(d,J=8.1Hz,2H),7.49(d,J=8.8Hz,1H),7.37(d,J=7.7Hz,3H),7.17(d,J=7.9Hz,2H),7.09(d,J=7.7Hz,3H),6.59(s,1H),2.35(s,3H);13C NMR(125MHz,CDCl3)δ176.06,165.89,145.29,142.25,138.75,135.34,133.92,129.73,129.33,128.62,127.61,125.53,117.68,114.59,81.42,45.46,21.53.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 2
A10 ml reaction flask was charged with 41mg of potassium carbonate, 78mg of N- [2- (4-ethyl-phenyl) -1- (pyridin-2-ylamino) -ethylidene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (3- (dibromomethyl) -3- (4-ethylphenyl) imidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide with a yield of 64%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.42(d,J=6.5Hz,1H),8.00(t,J=7.7Hz,1H),7.87(d,J=8.2Hz,2H),7.50(d,J=8.9Hz,1H),7.18(t,J=9.4Hz,4H),7.06(t,J=6.8Hz,1H),7.00(d,J=8.2Hz,2H),6.58(s,1H),2.65(q,J=7.5Hz,2H),2.36(s,3H),1.23(t,J=7.6Hz,3H);13C NMR(125MHz,CDCl3)δ176.28,166.01,146.12,144.77,142.12,138.89,135.34,131.23,128.78,128.56,127.68,127.54,125.47,117.70,114.00,81.36,45.66,28.40,21.52,15.15.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 3
A10 ml reaction flask was charged with 41mg of potassium carbonate, 80mg of N- [2- (4-chloro-phenyl) -1- (pyridin-2-ylamino) -ethylidene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 and ethyl acetate as an eluent until a final product, namely the 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, and the yield of (Z) -N- (3- (4-chlorphenyl) -3- (dibromomethyl) imidazo [1, 2-alpha ] pyridine-2 (3H) -subunit) -4-methylbenzenesulfonamide is 48 percent.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.41(s,1H),7.84(d,J=7.4Hz,2H),7.58(s,1H),7.42–7.37(m,2H),7.33–7.30(m,2H),7.18(d,J=7.4Hz,2H),7.05–7.02(m,2H),6.57(s,1H),2.35(s,3H);13C NMR(125MHz,CDCl3)δ175.65,165.93,145.55,142.53,138.50,136.05,135.20,132.46,129.57,129.05,128.76,127.56,127.27,127.03,117.97,114.90,45.15,21.55.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 4
A10 ml reaction flask was charged with 41mg of potassium carbonate, 77mg of N- [2- (4-fluoro-phenyl) -1- (pyridin-2-ylamino) -ethylidene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, followed by addition of 2ml of a methylene chloride solvent and nitrogen substitution three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product, 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative, specifically (Z) -N- (3- (dibromomethyl) -3- (4-fluorophenyl) imidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide, is obtained in 54% yield.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.42(d,J=6.5Hz,1H),8.02(t,J=8.1Hz,1H),7.87(d,J=8.1Hz,2H),7.51(d,J=8.9Hz,1H),7.19(d,J=7.9Hz,2H),7.14–7.10(m,2H),7.08(d,J=7.7Hz,3H),6.55(s,1H),2.37(s,3H);13C NMR(125MHz,CDCl3)δ175.79,165.67,145.39,142.17,138.62,135.19,129.86,128.47,127.70,127.64,127.37,117.42,116.29,116.11,114.74,80.83,45.37,21.33.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 5
A10 ml reaction flask was charged with 41mg of potassium carbonate, 79mg of N- [2- (4-methoxy-phenyl) -1- (pyridin-2-ylamino) -ethylidene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 and ethyl acetate as an eluent until a final product, namely the 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, and the yield of the (Z) -N- (3- (dibromomethyl) -3- (4-methoxyphenyl) imidazo [1, 2-alpha ] pyridine-2 (3H) -subunit) -4-methylbenzenesulfonamide is 76%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.42(d,J=6.5Hz,1H),8.00(t,J=7.7Hz,1H),7.88(d,J=8.1Hz,2H),7.49(d,J=8.8Hz,1H),7.18(d,J=7.9Hz,2H),7.04(dd,J=16.4,7.8Hz,3H),6.88(d,J=8.8Hz,2H),6.55(s,1H),3.82(s,3H),2.37(s,3H);13C NMR(125MHz,CDCl3)δ176.47,165.98,160.46,144.67,142.15,138.92,135.29,128.58,127.69,126.93,125.93,117.73,114.66,113.92,81.05,55.43,45.88,21.52.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 6
A10 ml reaction flask was charged with 41mg of potassium carbonate, 76mg of 4-methyl-N- [1- (pyridin-2-ylamino) -2-m-tolylethylene ] -benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was replaced three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 with ethyl acetate until the final product, 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative, specifically (Z) -N- (3- (dibromomethyl) -3- (m-tolyl) imidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide, is obtained in 69%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.40(d,J=6.5Hz,1H),8.01(t,J=7.7Hz,1H),7.84(d,J=8.2Hz,2H),7.49(d,J=8.8Hz,1H),7.24(t,J=7.7Hz,1H),7.19–7.14(m,3H),7.08(t,J=6.8Hz,1H),6.85(d,J=6.8Hz,2H),6.57(s,1H),2.32(d,J=19.1Hz,6H);13C NMR(125MHz,CDCl3)δ176.09,166.01,144.82,142.15,139.24,135.33,133.91,130.53,129.16,128.57,127.64,127.51,126.00,122.65,117.68,114.02,81.37,45.55,21.61,21.52.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 7
A10 ml reaction flask was charged with 41mg of potassium carbonate, 80mg of N- [2- (3-chloro-phenyl) -1- (pyridin-2-ylamino) -ethylidene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (3- (3-chlorophenyl) -3- (dibromomethyl) imidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide with a yield of 57%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.42(d,J=6.5Hz,1H),8.04(t,J=7.7Hz,1H),7.86(d,J=8.1Hz,2H),7.53(d,J=8.8Hz,1H),7.39(d,J=8.0Hz,1H),7.34(t,J=7.9Hz,1H),7.19(d,J=8.0Hz,2H),7.10(t,J=7.6Hz,2H),7.02(s,1H),6.53(s,1H),2.37(s,3H);13C NMR(125MHz,CDCl3)δ175.13,165.38,145.58,142.12,138.24,135.59,135.05,130.42,129.64,129.07,128.39,127.15,125.77,125.51,123.82,117.25,80.73,44.85,21.14.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 8
A10 ml reaction flask was charged with 41mg of potassium carbonate, 76mg of N- [1- (5-methyl-pyridin-2-ylamino) -2-phenyl-ethylene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, followed by addition of 2ml of a methylene chloride solvent and nitrogen substitution three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (3- (dibromomethyl) -6-methyl-3-phenylimidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide with a yield of 75%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.21(s,1H),7.86(t,J=8.4Hz,3H),7.45(d,J=9.0Hz,1H),7.39(d,J=7.6Hz,3H),7.17(d,J=8.0Hz,2H),7.09(d,J=6.9Hz,2H),6.61(s,1H),2.40(s,3H),2.36(s,3H);13C NMR(125MHz,CDCl3)δ176.01,164.56,147.34,142.03,134.11,133.07,129.78,129.64,129.27,128.86,128.73,128.54,127.87,127.63,125.60,124.73,121.09,117.20,81.68,45.60,21.51,18.04.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 9
A10 ml reaction flask was charged with 41mg of potassium carbonate, 80mg of N- [1- (5-chloro-pyridin-2-ylamino) -2-phenyl-ethylene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product, 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative, specifically (Z) -N- (6-chloro-3- (dibromomethyl) -3-phenylimidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide, is obtained in 58% yield.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.40(s,1H),7.99(d,J=9.2Hz,1H),7.84(d,J=8.1Hz,2H),7.59(d,J=9.5Hz,1H),7.40(d,J=7.4Hz,3H),7.18(d,J=7.9Hz,2H),7.09(d,J=6.9Hz,2H),6.55(s,1H),2.36(s,3H);13C NMR(125MHz,CDCl3)δ175.93,164.80,145.90,142.44,138.67,133.58,132.83,129.96,129.63,129.50,129.04,128.71,127.91,127.57,125.38,118.51,81.91,45.09,21.54.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 10
To a 10ml reaction flask, 41mg of potassium carbonate, N- [1- (5-chloro-pyridin-2-ylamino) -2- (4-ethyl-phenyl) -ethylidene ] -4-methyl-benzenesulfonamide and 85mg of carbon tetrabromide were added, followed by addition of 2ml of a methylene chloride solvent and nitrogen substitution three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 with ethyl acetate until the final product, 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative, in particular (Z) -N- (6-chloro-3- (dibromomethyl) -3- (4-ethylphenyl) imidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) benzenesulfonamide, is obtained with a yield of 46%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.40(s,1H),7.94(d,J=6.6Hz,2H),7.61–7.51(m,2H),7.48–7.43(m,2H),7.38(s,2H),7.23–7.19(m,2H),7.00–6.97(m,1H),6.57(s,1H),2.68–2.61(m,2H),1.22(d,J=6.6Hz,3H);13C NMR(125MHz,CDCl3)δ176.45,164.67,146.47,146.03,141.35,133.03,132.38,131.99,130.68,129.54,129.04,129.00,128.14,127.53,126.35,125.42,118.49,82.12,45.06,28.42,15.16.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 11
A10 ml reaction flask was charged with 41mg of potassium carbonate, 70mg of N- [ 2-N-butyl-1- (pyridin-2-ylamino) -ethylidene ] -4-methyl-benzenesulfonamide and 79mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (3-butyl-3- (dibromomethyl) imidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide with a yield of 65%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.27(d,J=6.4Hz,1H),7.94(dd,J=21.5,7.9Hz,3H),7.41(d,J=8.8Hz,1H),7.19(d,J=8.0Hz,2H),7.04(t,J=6.8Hz,1H),5.99(s,1H),2.34(s,3H),2.20(s,2H),2.06(s,2H),1.15–1.11(m,2H),0.69(t,J=7.3Hz,3H);13C NMR(125MHz,CDCl3)δ176.65,165.67,144.34,142.32,138.73,133.60,128.59,127.96,117.47,114.64,79.27,46.09,38.38,25.17,22.15,21.52,13.52.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 12
A10 ml reaction flask was charged with 41mg of potassium carbonate, 76mg of N- [ 2-phenyl-1- (pyridin-2-ylamino) -ethylidene ] -benzenesulfonamide and 70mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, in particular the (Z) -N- (3- (dibromomethyl) -3-phenylimidazo [1, 2-alpha ] ] pyridine-2 (3H) -ylidene) benzenesulfonamide yield is 49%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.43(d,J=4.3Hz,1H),7.98(d,J=7.6Hz,2H),7.60(d,J=5.9Hz,5H),7.54(s,1H),7.46(d,J=7.6Hz,2H),7.39(d,J=7.1Hz,3H),7.25(s,1H),7.09(d,J=6.5Hz,3H),6.60(s,1H);13C NMR(125MHz,CDCl3)δ176.20,165.73,145.51,143.23,135.47,131.98,129.54,129.28,128.79,127.93,127.42,126.08,125.51,117.46,114.89,81.53,45.33.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 13
A10 ml reaction flask was charged with 41mg of potassium carbonate, 76mg of N- [2- (4-ethyl-phenyl) -1- (pyridin-2-ylamino) -ethylidene ] -benzenesulfonamide and 70mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was replaced three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (3- (dibromomethyl) -3- (4-ethylphenyl) imidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) benzenesulfonamide yield is 47%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.42(d,J=6.1Hz,1H),7.97(d,J=7.9Hz,2H),7.49(d,J=8.4Hz,1H),7.43(d,J=7.6Hz,1H),7.37(d,J=7.0Hz,2H),7.18(d,J=7.5Hz,2H),7.07(dd,J=14.5,7.5Hz,2H),6.98(d,J=6.8Hz,2H),6.58(s,1H),2.65–2.62(m,2H),1.21(d,J=6.6Hz,3H);13C NMR(125MHz,CDCl3)δ176.48,165.92,146.16,145.06,135.39,131.69,128.81,128.22,127.93,127.63,125.47,117.63,114.34,81.47,45.52,28.39,15.17.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 14
A10 ml reaction flask was charged with 41mg of potassium carbonate, 73mg of N- [1- (5-methyl-pyridin-2-ylamino) -2-phenyl-ethylene ] -benzenesulfonamide and 70mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was replaced three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (3- (dibromomethyl) -6-methyl-3-phenylimidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) benzenesulfonamide yield is 65%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.19(s,1H),7.90(d,J=7.2Hz,3H),7.42(dd,J=17.0,7.9Hz,3H),7.37–7.33(m,4H),7.08–7.04(m,2H),6.62(s,1H),2.37(s,3H);13C NMR(125MHz,CDCl3)δ175.93,163.62,147.96,143.26,141.20,133.60,133.05,131.62,129.38,129.01,128.53,127.71,127.00,125.68,125.43,116.49,81.72,45.21,17.63.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 15
A10 ml reaction flask was charged with 41mg of potassium carbonate, 77mg of N- [1- (5-chloro-pyridin-2-ylamino) -2-phenyl-ethylene ] -benzenesulfonamide and 70mg of carbon tetrabromide, and then 2ml of a methylene chloride solvent was added, and nitrogen gas was replaced three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 as eluent, until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, specifically (Z) -N- (6-chloro-3- (dibromomethyl) -3-phenylimidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) benzenesulfonamide with a yield of 62%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.41(s,1H),8.00(d,J=8.4Hz,1H),7.96(d,J=7.6Hz,2H),7.59(d,J=9.1Hz,1H),7.49–7.43(m,2H),7.42–7.38(m,4H),7.09(d,J=6.9Hz,2H),6.56(s,1H);13C NMR(125MHz,CDCl3)δ176.05,164.62,145.97,141.20,133.32,132.80,131.89,129.93,129.45,129.00,128.02,127.80,127.41,125.27,118.40,81.93,44.82.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
Example 16
A10 ml reaction flask was charged with 41mg of potassium carbonate, 58mg of N- [ 2-phenyl-1- (pyridin-2-ylamino) -ethylidene ] -methanesulfonamide and 70mg of carbon tetrabromide, then 2ml of a methylene chloride solvent was added, and nitrogen gas was substituted three times; the reaction mixture was stirred at 100 ℃ for 12h under nitrogen protection. Tracking the reaction process by using thin layer chromatography until the reaction is finished (the volume ratio of petroleum ether/ethyl acetate is 2: 1 as a developing agent), cooling the reaction mixture to room temperature after the reaction is finished, filtering, and removing the solvent under reduced pressure to obtain a crude product; separating the crude product by column chromatography on silica gel column chromatography, and separating by volume ratio of 2: 1 with petroleum ether and ethyl acetate as eluent until the final product 3-dibromomethyl imidazo [1, 2-alpha ] pyridine derivative is obtained, in particular the (Z) -N- (3- (dibromomethyl) -3-phenylimidazo [1, 2-alpha ] pyridin-2 (3H) -ylidene) methanesulfonamide with a yield of 61%.
The final product obtained above was measured by an instrument AVANCE III 500M nmr, and the obtained nmr data on hydrogen spectrum and carbon spectrum are as follows:
1H NMR(500MHz,CDCl3)δ8.50(d,J=6.4Hz,1H),8.09(t,J=7.5Hz,1H),7.59(d,J=8.8Hz,1H),7.41(d,J=5.7Hz,3H),7.15(d,J=5.6Hz,3H),6.66(s,1H),3.15(s,3H);13C NMR(125MHz,CDCl3)δ176.80,165.98,145.12,135.43,129.89,129.46,125.50,117.58,114.24,81.37,45.89,39.93.
the final product can be obtained from the obtained nuclear magnetic resonance hydrogen spectrum and carbon spectrum data and is consistent with the predicted final product, the positions and the number of the peaks of the hydrogen spectrum are all consistent with the predicted condition, and the characteristic peaks of the carbon spectrum are obvious.
FIG. 1, FIG. 2 and FIG. 3 below are a single crystal spectrum, a hydrogen nuclear magnetic resonance spectrum and a carbon nuclear magnetic resonance spectrum, respectively, of (Z) -N- (3- (dibromomethyl) -3-phenylimidazo [1,2-a ] pyridin-2 (3H) -ylidene) -4-methylbenzenesulfonamide, a compound obtained in example 1.
The above description is only a basic description of the present invention, and any equivalent changes made according to the technical solution of the present invention should fall within the protection scope of the present invention.
Claims (3)
1. Preparation of 3-dibromo methyl imidazo [1, 2-alpha ]]A process for preparing a pyridine derivative, comprising: adding R into a reaction vessel1、R2、R3Substituted N- (2-pyridyl) amidines, CBr4Reacting the mixture with an organic solvent and a catalyst for 8 to 16 hours at the temperature of 100 ℃ and 120 ℃ under the protection of nitrogen, filtering, concentrating and separating by column chromatography after the reaction is finished to obtain the 3-dibromomethyl imidazo [1, 2-alpha ]]A pyridine derivative; said R1Is at least one of H, methyl and chlorine, R2Is at least one of phenyl, 4-ethylphenyl, 4-methoxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3-fluorophenyl, 4-fluorophenyl and n-butyl; r3Is at least one of 4-methylbenzene, phenyl and methyl; the catalyst is at least one of potassium carbonate, cesium carbonate, triethylamine, DBU, potassium tert-butoxide and lithium tert-butoxide; the organic solvent is dichloromethane, tetrahydrofuran and acetonitrile;
2. Preparation of 3-dibromomethylimidazo [1,2-a ] according to claim 1]A process for preparing pyridine derivatives, characterized in thatR of (A) to (B)1、R2、R3Substituted N- (2-pyridyl) amidines, CBr4The amount of catalyst, calculated in terms of molar ratio, R1、R2、R3Substituted N- (2-pyridyl) amidines, CBr4And the catalyst is 1-1.2: 1-1.2: 2 to 2.4.
3. Preparation of 3-dibromomethylimidazo [1,2-a ] according to claim 1]Process for preparing pyridine derivatives, characterized in that the organic solvent is used in an amount according to R1、R2、R3Substituted N- (2-pyridyl) amidines: organic solvent 0.1-0.5 mmol: the ratio of 1.5-2 mL.
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Non-Patent Citations (6)
Title |
---|
CBr4 Mediated Oxidative C-N Bond Formation: Applied in the Synthesis of Imidazo[1,2-α]pyridines and Imidazo[1,2-α]pyrimidines;Congde Huo et al.;《Org. Lett.》;20160216;第18卷;第1016-1019页 * |
Direct intramolecular double cross-dehydrogentive-coupling (CDC) cyclization of N-(2-pyridyl)amidines under metal-free conditions;Fengping Yi et al.;《RSC Advances》;20191219;第9卷(第72期);第42172-42182页 * |
Mild dehalogenative reduction of tri- and di-halogenomethyl compounds to lower halides by nickel tetracarbonyl;Takehisa Kunieda et al.;《Chemical & Pharmaceutical Bulletin》;19771231;第25卷(第7期);第1749-1755页 * |
Potent Inhibitors of tRNA-Guanine Transglycosylase, an Enzyme Linked to the Pathogenicity of the Shigella Bacterium: Charge-Assisted Hydrogen Bonding;Simone R. Hortner et al.1;《Angewandte Chemie, International Edition》;20071231;第46卷(第43期);第8266-8269页 * |
Tetrahalogenomethanes: simple reagents for the synthesis of monohalogenated and mixed dihalogenated aromatic heterocycles via metal–halogen exchange from lithium compounds;Carla Boga et al.;《Journal of Organometallic Chemistry》;20001231;第601卷;第233-236页 * |
甘氨酸衍生物α-C(sp3)—H 键官能团化反应的研究进展;祝志强等;《有机化学》;20190426;第39卷;第2345-2364页 * |
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