Process for the synthesis of trans-n-alkenylpyridin-2(1h)-ones

Abstract

The application relates to the organic chemical field, and particularly discloses a synthesis method of trans-N-alkenyl pyridine-2(1H)-ketone compounds. The pyridine ketone compound and the terminal alkyne compound are used as raw materials, a reaction is carried out in an organic solvent under the participation of a ruthenium catalyst and a phosphorus ligand, and the trans-N-alkenyl pyridine-2(1H)-ketone compound is obtained. The green synthesis method of the trans-N-alkenyl pyridine-2(1H)-ketone compound is realized through C-H bond activation under mild conditions, and has the advantages of wide raw material sources, simple operation, easy separation and purification, high yield and the like.

Description

Technical Field

[0001] The present invention relates to the fields of medicine, organic chemicals and fine chemicals, and in particular to a method for simply and efficiently synthesizing EN-alkenyl-pyridin-2(1H)-one (trans-N-alkenylpyridin-2(1H)-one) compounds by using pyridone compounds and terminal alkyne compounds as raw materials, in the presence of a ruthenium catalyst and a phosphorus ligand, and using 1,4-dioxane as a solvent. Background Art

[0002] 2-Pyridone fragments are present in many biologically relevant compounds, including some FDA-approved drugs for the treatment of cancer, HIV, and pulmonary fibrosis. Currently, these compounds are primarily synthesized via metal-catalyzed CH activation. Several synthetic methods are available, as shown below:

[0003]

[0004] Methods for preparing trans-N-alkenylpyridin-2(1H)-one compounds often use halides as starting materials, resulting in numerous reaction steps and complex conditions. Alternatively, vinylboronic acid and pyridone are coupled under an equivalent amount of copper catalysis to generate the product, or potassium alkenyltrifluoroborate and pyridone are cross-coupled under copper catalysis to effectively synthesize the product, or vinylbenzene and pyridone are synthesized under three equivalents of silver catalyst. These methods all require equivalent catalysts. Therefore, the development of a green synthesis method for the trans-N-alkenylpyridin-2(1H)-one series compounds through C-H bond activation under mild conditions is of great research value. Summary of the Invention

[0005] In light of the shortcomings of existing technologies, the present invention synthesizes a series of trans-N-alkenylpyridin-2(1H)-one compounds using inexpensive and readily available pyridone compounds and terminal alkyne compounds as starting materials in the presence of a transition metal ruthenium catalyst. The method of the present invention offers advantages such as a wide range of raw material sources, ease of operation, ease of separation and purification, and high yields.

[0006] The synthesis method of the trans-N-alkenylpyridin-2(1H)-one compound of the present invention is as follows: under a nitrogen atmosphere, under the action of a ruthenium catalyst, using the pyridone compound shown in Formula 1 and the terminal alkyne compound shown in Formula 2 as raw materials, with the participation of a phosphorus ligand, a reaction is carried out in an organic solvent to synthesize the target compound.

[0007] The specific process of this reaction is as follows:

[0008]

[0009] Wherein R1 is one of hydrogen, alkyl, fluorine, chlorine, bromine, methoxy, and ester groups; and R2 is one of aryl, substituted aryl, alkyl (C1-C10), and substituted alkyl (C1-C10).

[0010] Furthermore, the ruthenium catalyst is one of bis-(2-methylallyl)cycloocta-1,5-dieneruthenium (Ru(methallyl)2COD), ruthenium trichloride, bis(tricyclohexylphosphine)benzylideneruthenium dichloride), ruthenium iodide, and ruthenium acetate. Preferably, the ruthenium catalyst is bis-(2-methylallyl)cycloocta-1,5-dieneruthenium (Ru(methallyl)2COD).

[0011] Furthermore, the organic solvent is one of toluene, xylene, nitrobenzene, chlorobenzene, fluorobenzene, 1,4-dioxane, trifluorotoluene, and mesitylene. Preferably, the organic solvent is 1,4-dioxane.

[0012] Furthermore, the ligand is: 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine, with the structural formula Bipyridine, (2S,4S)-(-)-2,4-bis(diphenylphosphino)pentane, Xantphos, triisopropylphosphine, triisopropylphosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (Binap), 1,4-bis(diphenylphosphino)butane (dppb), (6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine), dppf, dppa, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos), 2-dicyclohexylphosphino-2',6'-dimethoxy-biphenyl (Sphos), N,N-dimethyl-dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine-4-amine, the structural formula is One of tricyclohexylphosphine, bis(dicyclohexylphosphino)methane, 1,2-bis(dicyclohexylphosphino)-ethane, 1,3-bis(dicyclohexylphosphino)propane, and 1,4-bis(dicyclohexylphosphino)butane

[0013] Furthermore, the reaction temperature is 80-120° C., and the reaction time is 15-26 h.

[0014] Furthermore, the equivalent ratio of the ruthenium catalyst, the phosphorus ligand, the pyridone compound, and the terminal alkyne compound is (0.05-0.10):(0.06-0.12):(1):(1-2). Preferably, the equivalent ratio of the ruthenium catalyst, the phosphorus ligand, the pyridone compound, and the terminal alkyne compound is 0.05:0.06:1:2.

[0015] Furthermore, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the target compound.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The present invention simplifies post-reaction processing, requiring only a simple column chromatography separation method using a mixed solvent of petroleum ether and ethyl acetate as an eluent to obtain a pure trans-N-alkenylpyridin-2(1H)-one compound. The pyridone and terminal alkyne raw materials used in the present invention are commercially available. The present invention provides a more concise and feasible route for the synthesis of trans-N-alkenylpyridin-2(1H)-one compounds, thus possessing significant application value. DETAILED DESCRIPTION

[0018] The present invention is described in detail below with reference to the embodiments. The reactions of the embodiments of the present invention are as follows:

[0019] Example 1

[0020] (E)-1-(4-Chlorostyryl)pyridin-2(1H)-one

[0021]

[0022] Under a nitrogen atmosphere, the catalyst (Ru(methallyl)2COD) (47.9 mg, 0.15 mmol, 5.0 mol%) and tributylphosphine ligand (0.18 mmol, 6.0 mol%) were dissolved in 6 mL of toluene and stirred for 5 minutes. This solution was then added to a 10 mL reaction vial containing pyridone (3 mmol, 1.0 equiv) and p-chlorophenylacetylene (3 mmol, 1.0 equiv) where R is p-chlorophenyl. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to obtain the title compound in a calculated yield of 47%.

[0023] NMR data: 1 H NMR (400MHz, CDCl3) δ7.98 (d, J = 14.9HZ, 1H), 7.61 (dd, J1 = 7.1HZ, J2 = 1.4Hz, 1H), 7.41-7.26 (m, 5H), 6.66-6.61 (m, 2H), 6.27 (t, J = 6.8HZ, 1H) ppm.

[0024] 13C NMR (100MHz, CDCl3) δ161.4,139.5,133.9,133.2,132.5,129.0,127.8,126.3,121.6,119.8,106.9ppm.

[0025] Example 1 (1)

[0026] On the basis of Example 1, the influence of the type of ruthenium catalyst was studied. Except for the ruthenium catalyst, other conditions were the same as those in Example 1.

[0027] Table 1

[0028] Ruthenium catalyst Yield Ruthenium trichloride 13％ (1,5-Cyclooctadiene)ruthenium chloride polymer <5％ Bis(tricyclohexylphosphine)benzylideneruthenium dichloride 16％ Ruthenium iodide 23％ Ruthenium acetate 12％ Triphenylphosphine ruthenium chloride <5％ Dichloro(pentamethylcyclopentadienyl)ruthenium(III) polymer <5％ Tris(2,2-bipyridyl)ruthenium chloride hexahydrate <5％

[0029] Example 1(2)

[0030] On the basis of Example 1, the influence of the solvent type was studied. Except for the solvent, other conditions were the same as those in Example 1.

[0031] Table 2

[0032] solvent Yield Toluene 47％ Xylene 38％ Nitrobenzene 24％ Tetrahydrofuran <5％ 1,2-Dichloroethane <5％ Chloroform <5％ Tetrachloromethane <5％ chlorobenzene 40％ Fluorobenzene 35％ dichloromethane <5％ 1,4-Dioxane 53％ Trifluorotoluene 15％ Mesitylene 36％ n-hexane 5％

[0033] From the above screening, 1,4-dioxane was selected as the optimal solvent.

[0034] Example 1(3)

[0035] The reaction catalyst is bis-(2-methylallyl)cycloocta-1,5-dieneruthenium, the stoichiometric ratio of pyridone to terminal alkyne is 1:1, the temperature is 90 degrees Celsius, the reaction solvent is 1,4-dioxane, and other reaction conditions are the same as in Example 1.

[0036] Under a nitrogen atmosphere, the catalyst (Ru(methallyl)2COD) (47.9 mg, 0.15 mmol, 5.0 mol%) and the ligand (6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 5 minutes. The mixture was then added to a 10 mL reaction vial containing pyridone (3 mmol, 1.0 equiv) and p-chlorophenylacetylene (3 mmol, 1.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to yield the title compound.

[0037] Study the effect of ligand type.

[0038] Table 3

[0039]

[0040]

[0041] The optimal ligand is 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine. The structure is as follows:

[0042]

[0043] Example 1(4)

[0044] (E)-1-(4-Chlorostyryl)pyridin-2(1H)-one

[0045]

[0046] Under a nitrogen atmosphere, the catalyst Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 5 minutes. The mixture was then added to a 10 mL reaction vial containing pyridone (R = H) (3 mmol, 1.0 equiv) and p-chlorophenylacetylene (R = p-chlorophenyl) (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford the title compound as a yellow solid (453 mg, calculated yield: 65%).

[0047] Example 1(5)

[0048] Compared with Example 1(4), the difference is that the equivalent ratio of ruthenium catalyst, ligand, pyridone and chlorophenylacetylene is different, and the other operations are the same as Example 1(4).

[0049] When the equivalent ratio of ruthenium catalyst, ligand, pyridone and chlorophenylacetylene is 0.05:0.06:1:1, the yield is 58%;

[0050] When the equivalent ratio of ruthenium catalyst, phosphoramidite ligand, pyridone and terminal alkyne is 0.05:0.06:1:1.5, the yield is 60%.

[0051] Example 1(6)

[0052] Based on the basic technology of Example 1(4), the effect of reaction temperature was studied.

[0053] Table 4

[0054]

[0055]

[0056] Example 2

[0057] (E)-1-(Dec-1-en-1-yl)-4-methylpyridin-2(1H)-one

[0058]

[0059] Under a nitrogen atmosphere, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This mixture was then added to a 10 mL reaction flask containing a Me-containing pyridone (3 mmol, 1.0 equiv) and deuterium (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 24 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 467 mg of the target compound as a clear liquid in a calculated yield of 63%.

[0060] NMR data: 1 H NMR (400MHz, CDCl3) δ7.27(d,J=6.68Hz,1H),7.20(d,J=14.32Hz,1H),7.10(d,J=6.64Hz,1H),6.04(t,J=6.84H z,1H),5.73-5.63(m,1H),2.13(q,J=7.36Hz,2H),2.07(s,3H),1.44-1.11(m,12H),0.81(t,J=6.96Hz,3H),ppm.

[0061] 13 C NMR (100MHz, CDCl3) δ161.8,136.4,131.1,130.1,126.9,122.9,105.9,31.8,30.0,29.34,29.27,29.2,29.1,22.6,17.2,14.0ppm.

[0062] Example 3:

[0063] (E)-4-Chloro-1-(dec-1-en-1-yl)pyridin-2(1H)-one

[0064]

[0065] Under a nitrogen atmosphere, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This mixture was then added to a 10 mL reaction vial containing a Cl-containing pyridone (3 mmol, 1.0 equiv) and deuterium (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 15 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 544 mg of the target compound as a clear liquid in a calculated yield of 68%.

[0066] NMR data: 1 H NMR (400MHz, CDCl3) δ7.39(d,J=7.48Hz,1H),7.11(d,J=14.28Hz,1H),6.57(d,J=2.12Hz,1H),6.19(dd,J =7.44Hz,1H),5.81-5.70(m,1H),2.17(q,J=6.96Hz,2H),1.50-1.14(m,12H),0.85(t,J=6.96Hz,3H)ppm.

[0067] 13 C NMR (100MHz, CDCl3) δ160.2,146.6,133.9,125.9,124.1,119.4,108.1,31.7,30.0,29.3,29.15,29.08,29.0,22.6,14.0ppm.

[0068] Example 4:

[0069] (E)-4-Chloro-1-(dec-1-en-1-yl)pyridin-2(1H)-one 5m

[0070]

[0071] Under a nitrogen atmosphere, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This mixture was then added to a 10 mL reaction flask containing a bromopyridone (3 mmol, 1.0 equiv) and deuterium (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 481 mg of the target compound as a clear liquid in a calculated yield of 62%.

[0072] NMR data: 1 H NMR (400MHz, CDCl3) δ7.31 (d, J = 7.44Hz, 1H), 7.11 (d, J = 14.28Hz, 1H), 6.79 (d, J = 2.08Hz, 1H), 6.33 (dd, J = 7.40Hz, 1H),5.82-5.72(m,1H),2.17(q,J=7.32Hz,2H),1.50-1.37(m,2H),1.35-1.18(m,10H),0.86(t,J=7.04Hz,3H),ppm.

[0073] 13 C NMR (100MHz, CDCl3) δ160.0,135.5,133.6,126.0,124.2,123.1,110.6,31.8,30.0,29.3,29.26,29.15,29.08,22.6,14.0ppm.

[0074] Example 5:

[0075] (E)-1-(Dec-1-en-1-yl)-5-methylpyridin-2(1H)-one

[0076]

[0077] Under nitrogen, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphatidyl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This was then added to a 10 mL reaction flask containing a pyridone (3 mmol, 1.0 equiv) and quinone (6 mmol, 2.0 equiv) where R is Me. The reaction mixture was stirred at 90°C for 25 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford the title compound as a clear liquid (475 mg, calculated yield: 65%).

[0078] NMR data: 1 H NMR (400MHz, CDCl3) δ7.23-7.15(m,2H),7.13(dd,J=9.28Hz,1H),6.46(d,J=9.24Hz,1H),5.77-5 .66(m,1H),2.15(q,J=7.56Hz,2H),2.05(s,3H),1.48-1.14(m,12H),0.84(t,J=7.04Hz,3H),ppm.

[0079] 13 C NMR (100MHz, CDCl3) δ160.6,142.0,130.8,126.5,122.6,120.7,115.2,31.8,30.0,29.3,29.2,29.1,29.0,22.6,17.1,14.0ppm.

[0080] Example 6:

[0081] (E)-5-Chloro-1-(dec-1-en-1-yl)pyridin-2(1H)-one

[0082]

[0083] Under nitrogen, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphatidyl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This mixture was then added to a 10 mL reaction flask containing a pyridone (3 mmol, 1.0 equiv) and quinone (6 mmol, 2.0 equiv) containing Cl. The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 475 mg of the target compound as a clear liquid in a calculated yield of 60%.

[0084] NMR data: 1 H NMR (400MHz, CDCl3) δ7.48(d,J=2.64Hz,1H),7.23(dd,J=9.72Hz,1H),7.14(d,J=14.24Hz,1H),6.50(d,J =9.72Hz,1H),5.82-5.71(m,1H),2.17(q,J=7.08Hz,2H),1.49-1.15(m,12H),0.85(t,J=7.00Hz,3H),ppm.

[0085] 13 C NMR (100MHz, CDCl3) δ159.6,140.2,131.1,125.8,123.9,122.0,113.0,31.7,30.0,29.3,29.12,29.07,29.0,22.6,14.1ppm.

[0086] Example 7:

[0087] (E)-1-(Dec-1-en-1-yl)pyridin-2(1H)-one

[0088]

[0089] Under nitrogen, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphatidyl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This mixture was then added to a 10 mL reaction flask containing a pyridone (R=H) (3 mmol, 1.0 equiv) and deuterated acetyl (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 363 mg of the target compound as a clear liquid in a calculated yield of 78%.

[0090] NMR data: 1 H NMR (400MHz, CDCl3) δ7.45(d,J=6.84Hz,1H),7.34-7.27(m,1H),7.22(d,J=14.32Hz,1H),6.54(d,J=9.20Hz,1H),6 .17(t,J=6.72Hz,1H),5.80-5.70(m,1H),2.19(q,J=7.28Hz,2H),1.52-1.15(m,12H),0.87(t,J=6.88Hz,3H),ppm.

[0091] 13 C NMR (100MHz, CDCl3) δ161.5,139.4,133.8,126.8,123.6,121.3,106.3,31.9,30.1,29.4,29.3,29.2,29.1,22.7,14.1ppm.

[0092] Example 8:

[0093] (E)-1-(Oct-1-en-1-yl)pyridin-2(1H)-one

[0094]

[0095] Under a nitrogen atmosphere, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This mixture was then added to a 10 mL reaction flask containing a pyridone (R=H) (3 mmol, 1.0 equiv) and octyne (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 467 mg of the target compound as a clear liquid in a calculated yield of 76%.

[0096] NMR data: 1 H NMR (400MHz, CDCl3) δ7.39(d,J=6.96Hz,1H),7.28-7.20(m,1H),7.17(d,J=14.32Hz,1H),6.49(d,J=9.16Hz,1H), 6.12(t,J=6.60Hz,1H),5.76-5.66(m,1H),2.14(q,J=6.60Hz,2H),1.45-1.15(m,8H),0.82(t,J=6.88Hz,3H),ppm.

[0097] 13 C NMR (100MHz, CDCl3) δ161.5,139.4,133.8,126.7,123.5,121.3,106.3,31.5,30.0,29.2,28.7,22.5,14.0ppm.

[0098] Example 9:

[0099] (E)-1-(Hept-1-en-1-yl)pyridin-2(1H)-one

[0100] exist

[0101]

[0102] Under a nitrogen atmosphere, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphaheptyl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. The mixture was then added to a 10 mL reaction vial containing pyridone (3 mmol, 1.0 equiv) and 1-heptyne (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 418 mg of the target compound as a clear liquid in a calculated yield of 73%.

[0103] NMR data: 1 H NMR (400MHz, CDCl3) δ7.46(d,J=6.88Hz,1H),7.33-7.27(m,1H),7.23(d,J=14.28Hz,1H),6.55(d,J=9.16Hz,1H), 6.18(t,J=6.64Hz,1H),5.81-5.73(m,1H),2.20(q,J=6.96Hz,2H),1.52-1.25(m,6H),0.89(t,J=6.84Hz,3H),ppm.

[0104] 13 C NMR (100MHz, CDCl3) δ161.6,139.3,133.7,126.7,123.6,121.3,106.3,31.3,30.0,29.0,22.4,14.0ppm

[0105] Example 10:

[0106] (E)-1-(Hex-1-en-1-yl)pyridin-2(1H)-one

[0107]

[0108] Under nitrogen, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphatidyl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. This was then added to a 10 mL reaction flask containing pyridone (3 mmol, 1.0 equiv) and 1-hexyne (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford the title compound as a clear liquid (441 mg, calculated yield: 83%).

[0109] NMR data: 1 H NMR (400MHz, CDCl3) δ7.47(dd,J=6.96Hz,1H),7.35-7.28(m,1H),7.24(d,J=14.32Hz,1H),6.56(d,J=9.16Hz,1H),6 .19(td,J=7.00Hz,1H),5.83-5.74(m,1H),2.22(qd,J=7.36Hz,2H),1.50-1.30(m,4H),0.92(t,J=7.16Hz,3H),ppm.

[0110] 13 C NMR (100MHz, CDCl3) δ161.4,139.3,133.7,126.7,123.4,121.2,106.2,31.3,29.6,22.1,13.8ppm.

[0111] Example 11:

[0112] (E)-1-(3-Phenylprop-1-en-1-yl)pyridin-2(1H)-one

[0113]

[0114] Under a nitrogen atmosphere, a ruthenium catalyst, such as Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%), and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. The mixture was then added to a 10 mL reaction vial containing pyridone (3 mmol, 1.0 equiv) and 4-phenyl-1-butyne (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 24 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford 532 mg of the target compound as a clear liquid in a calculated yield of 84%.

[0115] NMR data: 1 H NMR(400MHz, CDCl3) δ7.39(dd,J=6.96Hz,1H),7.34-7.24(m,4H),7.24-7.16(m,3H),6.55(d,J=9.20H z,1H),6.17(t,J=7.52Hz,1H),5.83-5.73(m,1H),2.79(t,J=7.32Hz,2H),2.53(q,J=6.96Hz,2H),ppm.

[0116] 13 C NMR (100MHz, CDCl3) δ161.3,140.8,139.4,133.6,128.4,128.3,127.2,126.0,122.2,121.2,106.3,35.6,31.7ppm.

[0117] Example 12:

[0118] (E)10-(2-oxopyridin-1(2H)-yl)dec-9-en-1-yl(R)-2-(6-methoxynaphthalen-2-yl)propanoate

[0119]

[0120] Under a nitrogen atmosphere, the ruthenium catalyst Ru(methallyl)2COD (47.9 mg, 0.15 mmol, 5.0 mol%) and the ligand 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphoryl)]-5H-dibenzo[b,f]azepine (73.7 mg, 0.18 mmol, 6.0 mol%) were dissolved in 6 mL of 1,4-dioxane and stirred for 10 minutes. The mixture was then added to a 10 mL reaction vial containing a pyridone (R = H) (3 mmol, 1.0 equiv) and a terminal alkyne (R = naproxen natural product fragment) (6 mmol, 2.0 equiv). The reaction mixture was stirred at 90°C for 26 hours. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 4:1) to afford the title compound as a clear liquid (997 mg, calculated yield: 65%).

[0121] NMR data: 1 H NMR (400MHz, CDCl3) δ7.62 (t, J=8.6H Z ,3H),7.46-7.39(m,2H),7.33-7.29(m,1H),7.22(d,J=14.3H Z ,1H),7.15-7.11(m,2H),6.56(d,J=9.2H Z ,1H),6.18(t,J=6.5H Z ,1H),5.79-5.71(m,1H),4.06(t,J=6.6H Z ,2H),3.90(s,3H),3.84(dd,J1=14.3H Z ,J2=7.2Hz,1H),2.16(dd,J1=14.1H Z ,J2=7.0Hz,2H),1.58-1.54(m,5H),1.42-1.36(m,2H),1.25-1.20(m,8H),ppm.

[0122] 13 C NMR(100 MHz, CDCl3)δ174.6,161.9,157.5,147.0,140.0,136.6,135.7,133.5,129.1,128.8,127.0,126.1,125 .8,118.8,117.9,112.3,111.0,105.4,64.8,55.1,45.4,29.3(2C),29.1,29.0,28.4,25.7,24.1,18.4 ppm.

Claims

1. A method for synthesizing a trans-N-alkenylpyridin-2(1H)-one compound, characterized in that: Using pyridone compounds and terminal alkyne compounds as raw materials, a reaction is carried out in an organic solvent in the presence of a ruthenium catalyst and a ligand to obtain a trans-N-alkenylpyridin-2(1H)-one compound; The structural formula of the pyridone compound is: ; The structural formula of terminal alkyne compounds is: The structural formula of trans-N-alkenylpyridin-2(1H)-one compounds is: ; Wherein R1 is one of hydrogen, alkyl, fluorine, chlorine, bromine, and methoxy; R2 is one of aryl and alkyl; The ruthenium catalyst is one of bis-(2-methylallyl)cycloocta-1,5-dieneruthenium, ruthenium trichloride, bis(tricyclohexylphosphine)benzylideneruthenium dichloride, ruthenium iodide, and ruthenium acetate; Among them, the ligands are 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphinoheptayl)]-5H-dibenzo[b,f]azepine, bipyridine, (2S,4S)-(-)-2,4-bis(diphenylphosphino)pentane, Xantphos, triisopropylphosphine, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (Binap), 1,4-bis(diphenylphosphino)butane (dppb), (6,6'-dimethoxy-[1,1'-biphenyl]-2,2'-diyl)bis(diphenylphosphine) , dppf, dppa, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos), 2-dicyclohexylphosphino-2',6'-dimethoxy-biphenyl (Sphos), N, N-dimethyldinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphine-4-amine, tricyclohexylphosphine, bis(dicyclohexylphosphino)methane, 1,2-bis(dicyclohexylphosphino)-ethane, 1,3-bis(dicyclohexylphosphino)propane, 1,4-bis(dicyclohexylphosphino)butane.

2. The method for synthesizing trans-N-alkenylpyridin-2(1H)-one compounds according to claim 1, characterized in that: The organic solvent is one of toluene, xylene, nitrobenzene, chlorobenzene, fluorobenzene, 1,4-dioxane, trifluorotoluene, and mesitylene.

3. The method for synthesizing trans-N-alkenylpyridin-2(1H)-one compounds according to claim 1, characterized in that: The reaction temperature is 80~120℃, and the reaction time is 15~26h.

4. The method for synthesizing trans-N-alkenylpyridin-2(1H)-one compounds according to claim 1, characterized in that: The equivalent ratio of the ruthenium catalyst, the ligand, the pyridone compound and the terminal alkyne compound is (0.05-0.10):(0.06-0.12):(1):(1-2).

5. The method for synthesizing trans-N-alkenylpyridin-2(1H)-one compounds according to claim 4, characterized in that: The equivalent ratio of the ruthenium catalyst, the ligand, the pyridone compound and the terminal alkyne compound is 0.05:0.06:1:

2.

6. The method for synthesizing trans-N-alkenylpyridin-2(1H)-one compounds according to claim 1, characterized in that: The catalyst is bis-(2-methylallyl)cycloocta-1,5-dieneruthenium; the ligand is 5-[6-(dibenzo[d,f][1,3,2]dioxaphosphaheptyl)]-5H-dibenzo[b,f]azepine; and the organic solvent is 1,4-dioxane.

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