A method for the synthesis of n-alkylated pyridin-2-one derivatives

Abstract

The application belongs to the field of organic chemical medicine, and relates to a synthesis method of N-alkylated pyridine-2-ketone derivatives. The application takes a sulfuryl hydrazone derivative and a pyridine-2-ketone derivative as raw materials, takes a rhodium salt as a catalyst, takes a base as an additive, further adds a proper solvent, seals argon gas reaction, reacts for a certain time at a certain temperature, removes the solvent by reducing pressure after the reaction is finished, and separates the target product through silica gel column chromatography or recrystallization. The synthesis of N-alkylated pyridine-2-ketone derivatives is realized. The method has the following advantages: the raw material is easy to obtain, the stable sulfuryl hydrazone derivative is used as a carbene precursor, and the method is safer; the substrate has wide adaptability, the reaction operation is simple, the reaction efficiency is high, the method is more in line with the requirements of green chemistry, and the derivative product has certain enantioselectivity.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical and pharmaceutical industries, and relates to a method for synthesizing N-alkylated pyridine-2-one derivatives using sulfonylhydrazone and pyridine-2-one as raw materials and rhodium salt as a catalyst. Background Technology

[0002] Pyridin-2-one structures are widely found in drug molecules and many natural products (Elmarrouni A, et al. J. Organic Letters, 2017, 19, 3071-3074. Healy AR, et al. JJ Am Chem Soc, 2016, 138, 5426-5432). Given the widespread distribution of N-alkylpyridin-2-ones in biomolecules (Hiort J, et al. J. Journal of Natural Products, 2005, 68: 1821-1821. Li L, et al. J. ACS medicinal chemistry letters, 2017, 8: 407-412.) and their unique biological activities, developing new methods for synthesizing more complex N-alkylpyridin-2-one derivatives is a prerequisite for their use in further efficient drug screening.

[0003] Because tautomerism can occur between 2-hydroxypyridine and 2-pyridone, direct N-alkylation of 2-pyridone is difficult to achieve, often resulting in a mixture of N- and O-alkylated products, making it impossible to obtain the target product with high chemoselectivity. Summary of the Invention

[0004] To address the problems in the background art, this invention provides a method for synthesizing N-alkylated pyridine-2-one derivatives using sulfonylhydrazones and pyridine-2-ones as raw materials and rhodium salts as catalysts. This invention uses sulfonylhydrazone derivatives and pyridine-2-one compounds as raw materials. First, the sulfonylhydrazone is situ-generated in situ under alkaline conditions with a base additive to form the corresponding diazo compound. Then, the rhodium catalyst activates the compound to generate a vinylrhodium carbene intermediate. Next, the lone pair electrons on the N-oxide of the 2-oxycarbonylpyridine electrophilically attack the vinylrhodium carbene to generate a nitrogen ylide intermediate. Finally, the product undergoes a five-membered ring transition state, i.e., intramolecular 1,4-acyl migration and rearrangement, to generate the final product. This method achieves the synthesis of N-alkylated pyridine-2-one derivatives using inexpensive and readily available raw materials. It has advantages such as readily available raw materials, broad substrate adaptability, simple reaction operation, and high reaction efficiency, and is more in line with the requirements of green chemistry.

[0005] To achieve the above technical objectives, the adopted technical solution is as follows:

[0006] This invention relates to a method for synthesizing N-alkylated pyridin-2-one derivatives. The reaction begins with the addition of a sulfonylhydrazone derivative, a pyridin-2-one derivative, and a rhodium catalyst, followed by the addition of a base additive, then an appropriate amount of solvent, and under argon protection. The reaction is carried out at 25°C-45°C for 8-12 hours. After the reaction is complete, the solvent is removed under reduced pressure, and the product is adsorbed onto silica gel. Separation is achieved by column chromatography or recrystallization with a mixed solvent to obtain the target product, the N-alkylated pyridin-2-one derivative.

[0007] The method for synthesizing N-alkylated pyridin-2-one derivatives is as follows:

[0008]

[0009] The Ar group consists of: 2-nitrobenzene, 2,4,6-triisopropylbenzene; the R1 group consists of: phenyl, 4-fluorophenyl, 4-dimethylaminophenyl, 4-methoxyphenyl, 4-methylphenyl, 2-methoxyphenyl, 2-bromophenyl, methyl, cyclohexyl, furan-2-yl; the R2 group consists of: hydrogen, 3-chloro, 3-methyl, 4-methyl, 5-methyl, 5-bromo, 5-trifluoromethyl; the R3 group consists of: diethylaminocarbonyl, valeryl, ethoxycarbonyl, benzyloxycarbonyl, benzoyl, acetyl; the R4 group consists of: hydrogen, phenyl; the R5 group consists of: hydrogen, methyl, phenyl; the R6 group consists of: hydrogen, methyl, phenylethynyl.

[0010] The rhodium catalysts used include: Rh2(OAc)4, Rh2(PTTL)4, Rh2(esp)2, Rh2(Oct)4, Rh2(OPiv)4, Rh2(S-TBPTTL)4, Rh2(s-TFPTTL)4, Rh2(s-PTV)4, Rh2(s-TCPTA)4, Rh2(s-PTAP)4, and Rh2(s-TBPTAP)4; the amount used is 0.5-2% of the molar number of the sulfonylhydrazone derivative, with Rh2(esp)2 being the optimal catalyst and the optimal amount used being 1% of the molar number of the sulfonylhydrazone compound.

[0011] The additive used is LiO t One of Bu, DIPEA, Et3N, DBU, DABCO, DMAP, and NaH is used in an amount of 0.5-2.5 equivalents of the amount of the sulfonylhydrazone derivative.

[0012] The sulfonylhydrazone derivatives have the following structures:

[0013]

[0014] Pyridin-2-one compounds include the following structures:

[0015]

[0016] The amount of pyridine-2-one compound used is 1 to 2.5 equivalents of the amount of sulfonylhydrazone derivative used.

[0017] The solvent used is one of dichloromethane, n-hexane, acetonitrile, diethyl ether, chloroform, toluene, tetrahydrofuran, or 1,2-dichloroethane, and the concentration of the sulfonylhydrazone derivative in the solvent is 0.05-0.2 mol / L.

[0018] First, add sulfonylhydrazone derivatives and pyridin-2-one derivatives and a rhodium catalyst, then add an alkaline additive, followed by an appropriate amount of solvent and argon protection. React at 25℃-45℃ for 8-12 hours. After the reaction, evaporate the solvent under reduced pressure. The product is purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5], or by recrystallization purification using an EA / PE system.

[0019] The reaction solvent is an organic solvent. Specifically, the organic solvent is one of dichloromethane, acetonitrile, diethyl ether, chloroform, toluene, tetrahydrofuran, and 1,2-dichloroethane.

[0020] The concentration of sulfonylhydrazone derivatives in solvents is 0.05–0.2 mol / L.

[0021] This invention synthesizes N-alkylated pyridin-2-one with high chemoselectivity under Rh catalysis by structural design using sulfonylhydrazone derivatives and pyridin-2-one derivatives as raw materials and careful screening of reaction conditions.

[0022] This invention achieves highly chemoselective synthesis of N-alkylated pyridine-2-one derivatives using sulfonylhydrazone and pyridine-2-one as starting materials and rhodium salt as a catalyst. The structures of all products are described in [the following text is missing from the original extract]. 1 H NMR, 13 Confirmed by C NMR, HRMS, and melting point. The reaction is simple to feed and has a wide range of substrates.

[0023] Beneficial effects:

[0024] 1) The reaction raw materials are readily available and easy to prepare.

[0025] 2) The reaction conditions are relatively mild.

[0026] 3) The substrate has wide adaptability and the yield is moderate to high.

[0027] 4) It has a certain degree of enantioselectivity, reaching 89% ee. Attached Figure Description

[0028] Figure 1 For compound 3aa 1 1H-NMR (H1N1 NMR);

[0029] Figure 2For compound 3aa 13 C-NMR (carbon nuclear magnetic resonance spectroscopy);

[0030] Figure 3 For compound 5 1 1H-NMR (H1N1 NMR);

[0031] Figure 4 For compound 5 13 C-NMR (carbon nuclear magnetic resonance spectroscopy);

[0032] Figure 5 HPLC (High Performance Liquid Chromatography) of compound 5. Detailed Implementation

[0033] The present invention will be further described below with reference to embodiments, but is not limited thereto.

[0034] Example 1

[0035]

[0036] 1. o-Nitrobenzenesulfonyl chloride was dissolved in tetrahydrofuran (THF). The reaction system was cooled to -15°C and stirred before adding 85% hydrazine hydrate (2 equivalents). The reaction was allowed to proceed overnight, then brought to room temperature. The mixture was extracted four times with ethyl acetate, dried over anhydrous magnesium sulfate, and slightly desaturated by vacuum distillation before crystallization with petroleum ether. The resulting yellow solid was filtered and washed three times with petroleum ether to obtain o-nitrobenzenesulfonamide.

[0037] 2. Mix the o-nitrobenzenesulfonamide (2.0 mmol) obtained in step 1 with methanol (5 mL), add cinnamaldehyde (1.0 eq), and stir at room temperature. After 1-2 hours of reaction, a solid precipitate was observed to form in the system. After the reaction was complete, filter using a Buchner funnel to obtain the solid. Some products did not form a solid precipitate; these could be purified by dry silica gel column chromatography. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 3] to give 1.2 g of yellow solid 1a, yield 90%; mp 120-121℃. 1 HNMR(400MHz,Chloroform-d)δ8.38-8.31(m,1H),8.30-8.26(m,1H),7.87-7.83(m,1H),7.79-7.75(m,2 H),7.70(d,J=8.7Hz,1H),7.29(d,J=8.0Hz,2H),7.14(d,J=8.0Hz,2H),6.86-6.70(m,2H),2.33(s,3H). 13C NMR (101MHz, CDCl3) δ152.49,148.21,141.53,139.84,134.35,133.02,132.92, 132.60,131.76,129.64,127.20,125.31,122.82,21.41.HRMS(ESI):calculated for C 16 H 16 N3O4S[M+Na]+m / z346.0856; found:346.0857

[0038]

[0039] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), catalyst Rh2 (esp) 21.6 mg (0.002 mmol), and 4 mL THF were added sequentially to the reaction tube. The reaction was sealed and purged with argon gas at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3aa 55.8 mg, yield 90%; mp: 98-100 °C. 1 H NMR(400MHz,Chloroform-d)δ(ppm)7.43–7.39(m,3H),7.38–7.29(m,4H),6.67–6.59(m,2H),6.4 0(dd,J=16.1,6.8Hz,1H),6.21(td,J=6.8,1.4Hz,1H),6.14(dd,J=6.8,1.5Hz,1H),1.50(s,9H). 13 C NMR (101MHz, CDCl3) δ (ppm) 168.12, 162.29, 139.77, 136.35, 136.03, 135.54, 128. 76,126.79,121.94,120.51,105.84,83.16,60.30,27.99.HRMS(ESI):calculated for C 25 H 25 NO3Na[M+Na]+:410.1727; Found:410.1721.

[0040] Example 1-1

[0041] Scale-up reaction: Sulfonylhydrazone derivatives 1a (1.192 g, 3.6 mmol), 2a (1.405 g, 7.2 mmol), and sodium hydride (0.129 g, 5.4 mmol) were added sequentially to a 100 mL reaction tube, followed by catalyst Rh2(esp) 227.3 mg (0.036 mmol) and 75 mL of THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was removed by vacuum distillation, and the product was purified by recrystallization to obtain a white solid 3aa (1.01 g), with a yield of 89%. The scale-up reaction showed good results and has certain industrial production value.

[0042] Example 2

[0043] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (PTTL) 42.4 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 19.9 mg of white solid 3aa, yield 32%.

[0044] Example 3

[0045] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 55.8 mg of white solid 3aa, yield 90%.

[0046] Example 4

[0047] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (Oct) 41.5 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 24.8 mg of white solid 3aa, yield 40%.

[0048] Example 5

[0049] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL LCM were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3aa 40.4 mg, yield 65%.

[0050] Example 6

[0051] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 97.5 mg (0.5 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 48.5 mg of white solid 3aa, yield 78%.

[0052] Example 7

[0053] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 50 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 41.0 mg of white solid 3aa, yield 66%.

[0054] Example 8

[0055] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), lithium tert-butoxide 24 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 47.9 mg of white solid 3aa, yield 77%.

[0056] Example 9

[0057] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 16 mg (0.4 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3aa 50.3 mg, yield 81%.

[0058] Example 10

[0059]

[0060] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 292 mg (2.0 mmol) of p-methylcinnamaldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain 630 mg of yellow solid 1b, with a yield of 88%; mp: 128-129 °C. 1 H NMR(400MHz,Chloroform-d)δ8.38-8.31(m,1H),8.30-8.26(m,1H),7.87-7.83(m,1H),7.79-7.75(m,2 H),7.70(d,J=8.7Hz,1H),7.29(d,J=8.0Hz,2H),7.14(d,J=8.0Hz,2H),6.86-6.70(m,2H),2.33(s,3H). 13C NMR (101MHz, CDCl3) δ152.49,148.21,141.53,139.84,134.35,133.02,132.92, 132.60,131.76,129.64,127.20,125.31,122.82,21.41.HRMS(ESI):calculated for C 16 H 16 N3O4S[M+Na]+m / z 346.0856; found:346.0857.

[0061]

[0062] Sulfonylhydrazone derivative 1b 69.1 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ab 45.5 mg, yield 70%; mp: 121-123 °C. 1 H NMR(400MHz,Chloroform-d)δ7.43–7.40(m,1H),7.35(ddd,J=8.9,6.6,2.1Hz,1H),7.30(d,J=8.1Hz,2H),7.15(d,J=7.9Hz,2H),6.62(d,J=11 .4Hz,1H),6.60–6.57(m,1H),6.33(dd,J=16.0,6.9Hz,1H),6.20(td,J=6.8,1.4Hz,1H),6.11(dd,J=6.9,1.4Hz,1H),2.35(s,3H),1.50(s,9H). 13 C NMR (101MHz, CDCl3) δ168.26,162.33,139.73,138.75,136.43,136.01,132.77,129 .45,126.71,120.74,120.47,105.78,83.08,60.34,27.98.HRMS(ESI):calculated for C 20 H 23 NO3Na[M+Na]+:348.1570; Found:348.1570.

[0063] Example 11

[0064]

[0065] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 324 mg (2.0 mmol) of p-methoxycinnamate, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain a yellow solid of 1 c 642 mg, yield 90%; mp: 146-147 °C. 1 H NMR (400MHz, Chloroform-d) δ8.31 (s, 1H), 8.29-8.25 (m, 1H), 7.88-7.81 (m, 1H), 7.79-7.73 (m, 2H), 7.70 (d, J = 9. 1Hz,1H),7.36-7.31(m,2H),6.85-6.84(m,2H),6.81(d,J=16.0Hz,1H),6.67(dd,J=16.0,9.1Hz,1H),3.80(s,3H). 13 C NMR (101MHz, CDCl3) δ160.73,152.80,148.21,141.23,134.32,133.05,132.91, 131.78,128.75,128.10,125.32,121.56,114.36,55.39.HRMS(ESI):calculated for C 16 H 16 N3O5S[M+H]+m / z 362.0805; found:362.0804..

[0066]

[0067] Sulfonylhydrazone derivative 1c 69.1 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ac 49.1 mg, yield 72%; mp: 123-125 °C. 1H NMR (400MHz, Chloroform-d): δ7.42(m,1H),7.37-7.32(m,3H),6.88(m,2H),6.63-6. 56(m,2H),6.27-6.18(m,2H),6.09(dd,J=7.0,1.4Hz,1H),3.82(s,3H),1.50(s,9H). 13 C NMR (101MHz, CDCl3): δ168.35,162.35,160.05,139.71,136.13,135.98,128.11,119.38,114.15,105.78,83.03,60.46,55.37,27.99.HRMS(ESI):calculated forC 20 H 23 NO4Na[M+Na]+:364.1519; Found:364.1519.

[0068] Example 12

[0069]

[0070] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 300 mg (2.0 mmol) of p-fluorocinnamaldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain a yellow solid of 620 mg 1 d, yield 88%; mp: 163-164 °C. 1 H NMR(400MHz,Chloroform-d)δ8.31-8.24(m,1H),7.88-7.81(m,1H),7.79-7.74(m,2H),7.72(d,J=9.3Hz,1H),7 .40(dd,J=7.7,1.7Hz,1H),7.28(td,J=7.8,1.6Hz,1H),7.19(d,J=16.2Hz,1H),6.94-6.82(m,3H),3.84(s,3H). 13 C NMR (101MHz, CDCl3) δ157.40,153.22,148.20,136.81,134.35,133.02,132.92,131. 75,130.72,127.61,125.31,124.27,120.81,111.07,55.50.HRMS(ESI):calculated forC 16 H 16N3O5S[M+H]+m / z 362.0805; found:362.0805

[0071]

[0072] Sulfonylhydrazone derivative 1d 69.8 mg (0.2 mmol), pyridine-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), followed by catalyst Rh2(esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was removed by vacuum distillation. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 49.2 mg of white solid 3ad, yield 75%; mp: 119-120 °C; 1H NMR (400 MHz, Chloroform-d) δ 7.41-7.39 (m, 1H), 7.38 (m, 2H), 7.35 (m, 1H), 7.03 (m, 2H), 6.61-6.59 (d, J = 8.7 Hz) 1H),6.60-6.56(dd,J=16.0,5.6Hz,1H),6.34(dd,J=16.0,6.7Hz,1H),6.22(td,J=6.8,1.4Hz,1H),6.10(dd,J=6.8,1.4Hz,1H),1.50(s,9H).13C NMR (101MHz, CDCl3) δ (ppm) 168.02, 162.24, 139.77, 136.00, 134.98, 128. 47,128.39,121.79,120.58,115.84,115.62,105.90,83.23,60.34,27.97.

[0073] 19F NMR (282MHz, CDCl3): δ (ppm)-112.10.

[0074] HRMS(ESI): calculated for C 19 H 20 FNO3Na[M+Na]+m / z 352.1319; found:352.1319.

[0075] Example 13

[0076]

[0077] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 350 mg (2.0 mmol) of p-dimethylaminocinnamaldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain 630 mg of yellow solid 1e, with a yield of 84%; mp: 124-125 °C. 1 H NMR(400MHz,Chloroform-d)δ8.29-8.24(m,1H),8.20(s,1H),7.86-7.82(m,1H),7.77-7.73(m,2H),7.69(d, J=9.3Hz,1H),7.32-7.27(m,2H),6.78(d,J=15.9Hz,1H),6.65-6.61(m,2H),6.61-6.55(m,1H),2.98(s,6H). 13 C NMR (101MHz, CDCl3) δ154.07,151.20,142.36,134.21,133.11,132.86,131.89, 129.69,128.76,125.29,123.27,118.83,111.96,40.21.HRMS(ESI):calculated for C 17 H 18 N4O4SNa[M+Na]+m / z 397.0941; found:397.0940.

[0078]

[0079] Sulfonylhydrazone derivative 1e 74.8 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a yellow solid 3ae 55.2 mg, yield 78%; mp: 103-104 °C. 1 H NMR(400MHz,Chloroform-d)δ7.47(m,1H),7.37-7.33(m,1H),7.31(m,2H),6.69(m,1H),6.67(m,1H),6.62-6.58(m,1H),6.57(m 1H),6.18(td,J=6.8,1.4Hz,1H),6.12(dd,J=15.7,7.3

[0080] Hz, 1H), 6.03 (dd, J = 7.3, 1.1Hz, 1H), 2.98 (s, 6H), 1.49 (s, 9H). 13 C NMR (101MHz, CDCl3)δ

[0081] 168.68,162.44,139.63,137.09,135.95,127.92,120.34,112.29,105.60,82.78,60.71,40.51,27.99.HRMS(ESI):calculated for C 21 H 26 N2O3Na[M+Na]+:377.1836; Found:377.1834.

[0082] Example 14

[0083]

[0084] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 324 mg (2.0 mmol) of o-methoxycinnamate, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain 1 f 642 mg of yellow solid, yield 90%; mp: 161-162 °C. 1 H NMR(400MHz,Chloroform-d)δ8.31-8.24(m,1H),7.88-7.81(m,1H),7.79-7.74(m,2H),7.72(d,J=9.3Hz,1H),7 .40(dd,J=7.7,1.7Hz,1H),7.28(td,J=7.8,1.6Hz,1H),7.19(d,J=16.2Hz,1H),6.94-6.82(m,3H),3.84(s,3H). 13 C NMR (101MHz, CDCl3) δ157.40,153.22,148.20,136.81,134.35,133.02,132.92,131. 75,130.72,127.61,125.31,124.27,120.81,111.07,55.50.HRMS(ESI):calculated forC 16 H 16 N3O5S[M+H]+m / z 362.0805; found:362.0805.

[0085]

[0086] Sulfonylhydrazone derivative 1f 72.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3af 58.6 mg, yield 75%; mp: 176-177 °C; 1 H NMR(400MHz,Chloroform-d)δ7.48-7.42(m,2H),7.35(m,1H),7.31-7.27(m,1H),7.02(dd,J=16.2,1.5Hz,1H),6.94(m,1H),6.89(m ,1H),6.59(m,1H),6.39(dd,J=16.2,6.9Hz,1H),6.20(td,J=6.8,1.4Hz,1H),6.13(dd,J=6.9,1.5Hz,1H),3.84(s,3H),1.51(s,9H). 13 C NMR (101MHz, CDCl3) δ168.39,162.38,157.04,139.71,136.12,131.85,129.80,127.25,124.48 ,122.17,120.67,120.37,110.97,105.68,82.96,60.64,55.45,27.96.HRMS(ESI):calculated for C 20 H 23 NO4Na[M+Na]+:364.1519; Found:364.1518.

[0087] Example 15

[0088]

[0089] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 422 mg (2.0 mmol) of o-bromocinnamaldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the product was filtered to obtain 1 g (730 mg) of yellow solid, with a yield of 89%; mp: 184-185 °C. 1H NMR (400MHz, Chloroform-d) δ8.31–8.24(m,1H),7.89–7.82(m,1H),7.81–7.74(m,3H),7.56(dd,J=8.0,1. 3Hz,1H),7.52(dd,J=7.9,1.6Hz,1H),7.30–7.21(m,3H),7.17-7.12(m,1H),6.76(dd,J=16.0,9.2Hz,1H). 13 C NMR(100MHz,DMSO-d6)δ149.47,147.85,137.13,134.76,134.71,133.05,132.77,131 .16,130.67,130.25,128.15,127.61,127.57,124.76,123.59.HRMS(ESI):calculated for C 15 H 13 BrN3O4S[M+H]+m / z 409.9805; found:409.9810.

[0090]

[0091] 1 g (82 mg, 0.2 mmol) of sulfonylhydrazone derivative, 78 mg (0.4 mmol) of pyridin-2-one derivative 2a, and 12 mg (0.3 mmol) of sodium hydride were added sequentially to the reaction tube, followed by 21.6 mg (0.002 mmol) of catalyst Rh2 (esp) and 4 mL of THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 3] to give 3 ag (59.2 mg) of yellow solid, yield 76%; mp: 116-117 °C. 1 H NMR(400MHz,Chloroform-d)δ7.58-7.51(m,2H),7.44-7.36(m,2H),7.30(m,1H),7.18-7.08(m,2H),6.99(dd, J=16.0,1.7Hz,1H),6.63-6.59(m,1H),6.35(dd,J=16.0,6.2Hz,1H),6.23(qd,J=6.6,1.6Hz,2H),1.52(s,9H). 13C NMR (101MHz, CDCl3) δ167.71,162.25,139.92,136.27,134.50,133.08,129.85,127 .71,127.29,125.33,120.54,105.96,83.43,60.08,28.03.HRMS(ESI):calculated for C 19 H 20 BrNO3Na[M+Na]+:412.0519; Found:412.0514.

[0092] Example 16

[0093]

[0094] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 244 mg (2.0 mmol) of the corresponding aldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain a yellow solid of 400 mg per 1 h, with a yield of 75%; mp: 123-124 °C. 1 H NMR(400MHz,DMSO-d6)δ12.05(s,1H),8.06-8.00(m,1H),8.00-7.95(m,1H),7.94-7.86(m,2H),7.83(d ,J=9.6Hz,1H),7.79-7.70(m,1H),6.92(d,J=15.9Hz,1H),6.72(m,1H),6.57(m,1H),6.55-6.46(m,1H). 13 C NMR (75MHz, CDCl3) δ151.94,151.54,148.17,144.15,134.36,133.04,132.92,131.67,128.05,125.28,121.79,112.55,112.24.HRMS(ESI): calculated for C 13 H 12 N3O5S[M+H]+m / z 322.0492; found:322.0493.

[0095]

[0096] Sulfonylhydrazone derivative 1h 64.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 3ah 25.8 mg of yellow solid, yield 43%; mp: 121-123 °C. 1 H NMR(400MHz,Chloroform-d)δ7.44-7.38(m,2H),7.38-7.33(m,1H),6.60(d,J=9.2Hz,1H),6.47-6. 39(m,2H),6.36-6.28(m,2H),6.22(td,J=6.8,1.5Hz,1H),6.13(dd,J=6.7,1.2Hz,1H),1.49(s,9H). 13 C NMR (101MHz, CDCl3) δ168.01,162.31,151.16,142.92,139.84,135.99,124.22,120 .43,120.05,111.63,110.20,105.94,83.24,59.88,27.97.HRMS(ESI):calculated for C 17 H 19 NO4Na[M+Na]+:324.1206; Found:324.1206.

[0097] Example 17

[0098]

[0099] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 140 mg (2.0 mmol) of the corresponding aldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the product was filtered to obtain 1 i 274 mg of yellow solid, yield 51%; mp: 107-109 °C. 1H NMR(400MHz,DMSO-d6)δ11.79(s,1H),8.06–7.98(m,1H),7.97–7.91(m,1H),7.89(dd,J=6.4,3.0Hz,2H), 7.68(d,J=9.2Hz,1H), 6.18(dd,J=15.4,6.9Hz,1H), 6.04(dd,J=15.7,9.2Hz,1H), 1.79(d,J=6.6Hz,3H). 13 C NMR(75MHz, CDCl3)δ152.69,148.13,140.93,134.36,132.89,131.61,127.53,125.23,119.61,18.60.HRMS(ESI):calculated for C 10 H 12 N3O4S[M+H]+m / z 270.0543; found:270.0544

[0100]

[0101] Sulfonylhydrazone derivative 1i 53.8 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ai 33.8 mg, yield 68%; mp: 89-90 °C; 1 HNMR(400MHz,Chloroform-d)δ7.33-7.23(m,2H),6.50(m,1H),6.13(m,1H),5.83(d,J=6.6Hz,1H ),5.75(dd,J=15.2,6.8Hz,1H),5.62(dd,J=15.5,6.7Hz,1H),1.73(d,J=6.3Hz,3H),1.40(s,9H). 13 C NMR (101MHz, CDCl3) δ168.47,162.30,139.59,135.91,133.60,123.83,120.35,105.58,82.75,60.16,27.93,18.17.HRMS(ESI):calculated for C 14 H 19NO3Na[M+Na]+:272.1257; Found:272.1257

[0102] Example 18

[0103]

[0104] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 276 mg (2.0 mmol) of the corresponding aldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain 1621 mg of white solid, yield 92%; mp: 130-131 °C. 1 H NMR(400MHz,Chloroform-d)δ8.24(m,1H),7.84(m,1H),7.77-7.73(m,2H),7.53(m,1H),6.09-6.04(m,2H),2.1 1-2.00(m,1H),1.74-1.66(m,4H),1.26(m,1H),1.23(m,1H),1.21-1.15(m,1H),1.11(m,1H),1.08-0.99(m,2H). 13 C NMR (101MHz, CDCl3) δ153.17,151.46,148.19,134.29,133.01,132.91,131.76,125.28,123.72,40.84,31.96,25.93,25.74.HRMS(ESI): calculated for C 15 H 19 N3O4S[M+H]+m / z 338.1169; found:338.1168

[0105]

[0106] Sulfonylhydrazone derivative 1j 67.5 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3aj 22.8 mg, yield 36%; mp: 93-94 °C; 1HNMR(400MHz,Chloroform-d)δ7.33-7.22(m,2H),6.54-6.46(m,1H),6.11(td,J =6.8,1.4Hz,1H),5.83(d,J=6.7Hz,1H),5.69(ddd,J=15.8,6.7,1.3Hz,1H),5.5 3(ddd,J=15.7,6.8,1.3Hz,1H),2.05-1.90(m,1H),1.71-1.56(m,5H),1.39(s,9 H),1.27-1.21(m,1H),1.21-1.17(m,1H),1.15(m,1H),1.09(m,1H),1.04(m,1H). 13 C NMR (101MHz, CDCl3) δ168.54,162.31,144.52,139.52,135.76,120.26,105.50, 82.52,59.98,40.61,32.41,32.36,27.91,25.95,25.77.HRMS(ESI):calculated for C 19 H 27 NO3Na[M+Na]+:340.1883; Found:340.1882

[0107] Example 19

[0108]

[0109] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 416 mg (2.0 mmol) of the corresponding aldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain 1 kJ of white solid (730 mg), yield 89%; mp: 148-149 °C. 1 H NMR(400MHz,Chloroform-d)δ8.33-8.30(m,1H),7.89-7.86(m,1H),7.82-7.79(m,2H),7.59(d,J=9.6Hz,1H),7.4 6-7.43(m,3H),7.42-7.37(m,1H),7.35-7.30(m,3H),7.29-7.26(m,2H),7.20-7.16(m,2H),6.80(d,J=9.7Hz,1H). 13C NMR (101MHz, CDCl3) δ152.37,150.86,148.16,140.33,137.71,134.34,133.00,132.92,131. 83,130.23,129.16,128.74,128.57,128.46,127.97,125.29,122.27.HRMS(ESI):calculated forC 21 H 18 N3O4S[M+H]+m / z408.1013; found:408.1616

[0110]

[0111] Sulfonylhydrazone derivative 1k 81.4 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ak 51.9 mg, yield 80%; mp: 102-104 °C. 1 H NMR (300MHz, Chloroform-d): δ (ppm) 7.42-7.34 (m, 3H), 7.34-7.25 (m, 6H), 7.22 (dd, J = 7.1, 1.7Hz, 1H), 7.18-7.11 (m,2H),6.52(d,J=9.3,1H),6.46(d,J=9.6Hz,1H),6.13(td,J=6.8,1.3Hz,1H),5.38(d,J=9.6Hz,1H),1.47(s,9H). 13 C NMR (75MHz, CDCl3): δ (ppm) 168.3, 162.1, 149.5, 140.9, 139.6, 138.3, 136.2, 129.4, 128.8, 1 28.5,128.4,128.3,127.7,120.9,120.1,105.8,82.7,61.5,28.0.HRMS(ESI):calculatedfor C 25 H 25 NO3Na[M+Na]+:410.1727; Found:410.1721

[0112] Example 20

[0113]

[0114] Add 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 292 mg (2.0 mmol) of the corresponding aldehyde, and 5 mL of CH3OH to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain 1 L of white solid (587 mg), yield 85%; mp: 168-169 °C. 1 H NMR(400MHz,Chloroform-d)δ8.32-8.29(m,1H),7.89-7.84(m,1H),7.82-7.78(m,2H),7.73(s,1H) ),7.40(m,1H),7.38-7.34(m,3H),7.34-7.29(m,1H),6.75(d,J=1.7Hz,1H),2.04(d,J=1.3Hz,3H). 13 C NMR (101MHz, CDCl3) δ155.63,148.29,139.35,135.96,134.34,133.48,133.06,132.65,131.57,129.44,128.45,128.14,125.19,12.87.

[0115]

[0116] Sulfonylhydrazone derivative 1L 69.1 mg (0.2 mmol), pyridin-2-one derivative 2A 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give 3Al 57.9 mg of white solid, yield 89%; mp: 121-122 °C. 1 H NMR(400MHz,Chloroform-d)δ7.46(m,1H),7.43-7.32(m,3H),7.36-7.27(m,3H),6.61(d d,J=9.4,1.4Hz,2H),6.58(s,1H),6.26-6.18(m,2H),1.87(d,J=1.4Hz,3H),1.52(s,9H). 13CNMR(101MHz,CDCl3)δ168.38,162.84,139.82,136.17,135.30,132.05,132.00,128.9 9,128.42,127.57,120.33,105.79,83.05,63.93,28.03,17.23.HRMS(ESI):calculated for C 20 H 23 NO3Na[M+Na]+:348.1570; Found:348.1570

[0117] Example 21

[0118]

[0119] 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 292 mg (2.0 mmol) of the corresponding ketone, and 5 mL of CH3OH were added to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain 1 mL of 440 mg of white solid, with a yield of 63%; mp: 106-107 °C. 1 H NMR(400MHz,Chloroform-d)δ8.35-8.31(m,1H),8.23(s,1H),7.87-7.83(m,1H),7.78(m,2H),7. 44-7.38(m,2H),7.37-7.27(m,3H),6.90(d,J=16.6Hz,1H),6.80(d,J=16.5Hz,1H),2.11(s,3H). 13 C NMR (101MHz, CDCl3) δ155.69,148.24,135.73,135.16,134.36,133.21,132.91, 131.78,129.00,128.87,127.87,127.12,125.34,11.49.HRMS(ESI):calculated for C 16 H 16 N3O4S[M+H]+m / z 346.0856; found:346.0855

[0120]

[0121] Sulfonylhydrazone derivative 1m 69.1 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3am 41.6 mg, yield 64%; mp: 153-154 °C. 1 H NMR(400MHz,Chloroform-d)δ7.48(m,1H),7.47-7.43(m,2H),7.37(m,1H),7.35(m,1H),7.33(m,1H),7.31(m,1H),6.75(d, J=16.3Hz,1H),6.57(dd,J=9.2,1.4Hz,1H),6.52(d,J=16.3Hz,1H),6.16(td,J=6.8,1.5Hz,1H),1.85(s,3H),1.47(s,9H). 13 C NMR (101MHz, CDCl3) δ168.95,162.08,139.28,135.74,134.21,134.03,128.83,128.70 ,127.92,126.91,121.32,105.77,81.95,68.02,27.85,20.25.HRMS(ESI):calculated for C 20 H 23 NO3Na[M+Na]+:348.1570; Found:348.1569

[0122] Example 22

[0123]

[0124] 434 mg (2.0 mmol) of nitrobenzenesulfonyl chloride, 412 mg (2.0 mmol) of the corresponding ketone, and 5 mL of CH3OH were added to a 50 mL reaction tube. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the mixture was filtered to obtain a white solid of 1n 586 mg, yield 68%; mp: 159-160 °C. 1H NMR(400MHz,Chloroform-d)δ9.38(s,1H),8.27-8.23(m,1H),7.86-7.80(m,2H) ),7.76-7.70(m,1H),7.69-7.60(m,4H),7.42-7.34(m,3H),7.33-7.28(m,3H). 13 CNMR(101MHz,CDCl3)δ148.28,138.32,134.51,133.64,132.98,132.54,132.52,130 .73,130.61,128.89,128.55,126.85,125.41,120.09,105.60HRMS(ESI):calculated forC 21 H 15 N3O4S[M+H]+m / z 406.0856; found:406.0858

[0125]

[0126] Sulfonylhydrazone derivative 1n 86.2 mg (0.2 mmol), pyridin-2-one derivative 2a 78 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3an 20.7 mg, yield 40%; mp: 149-150 °C; 1 H NMR(400MHz,Chloroform-d)δ7.81(m,1H),7.79(m,1H),7.54(m,2H),7.49-7.44 (m,2H),7.43(m,2H),7.39-7.35(m,3H),6.63(m,1H),6.15(m,1H),1.52(s,9H). 13 C NMR (101MHz, CDCl3) δ164.96,162.08,139.60,134.93,134.79,131.99,129.16,129.05,128.94,128.5 0,128.50,128.35,121.96,121.21,105.62,88.85,85.52,83.20,69.21,27.69.HRMS(ESI):calculated for C 25H 23 NO3Na[M+Na]+:408.1570; Found:408.1568.

[0127] Example 23

[0128]

[0129] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2b 83.6 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ba 52.6 mg, yield 80%; mp: 135-136 °C. 1 H NMR(400MHz,Chloroform-d)δ7.42-7.38(m,2H),7.37-7.32(m,2H),7.32-7.28(m,2H),7.24-7.20(m,1H),6.63(dd,J=1 6.1,1.4Hz,1H),6.41(dd,J=16.0,6.8Hz,1H),6.17(dd,J=6.8,1.4Hz,1H),6.16-6.11(m,1H),2.17(s,3H),1.50(s,9H). 13 CNMR(101MHz,CDCl3)δ168.39,162.68,137.00,136.12,135.65,133.30,129.46,128.7 6,128.62,126.78,122.27,105.53,83.05,60.50,28.03,17.44.HRMS(ESI):calculated forC 20 H 23 NO3Na[M+Na]+:348.1570; Found:348.1569.

[0130] Example 24

[0131]

[0132] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2c 91.8 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ca 56.0 mg, yield 81%; mp: 134-135 °C. 1 H NMR(400MHz,Chloroform-d)δ7.50(m,1H),7.36-7.31(m,3H),7.29-7.28(m,1H),7.28-7.26(m,1H),7.25-7.22(m,1H), 6.61(dd,J=16.0,1.4Hz,1H),6.30(dd,J=16.0,7.0Hz,1H),6.14-6.11(m,1H),6.09(dd,J=7.0,1.4Hz,1H),1.43(s,9H). 13 C NMR (101MHz, CDCl3) δ167.74,158.80,137.82,137.05,134.67,128.89,128.82,126.84,121.34,105.04,83.54,61.39,28.01.HRMS(ESI):calculated for C 19 H 20 ClNO3Na[M+Na]+:368.1024; Found:368.1024.

[0133] Example 25

[0134]

[0135] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2d 91.8 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3da 55.2 mg, yield 85%; mp: 114-116 °C. 1H NMR(400MHz,Chloroform-d)δ7.34-7.31(m,2H),7.29(m,1H),7.25(m,2H),7.22(m,1H),6.55(dd,J=16.0,1.4Hz,1 H),6.38(m,1H),6.31(dd,J=16.0,6.6Hz,1H),6.06(dd,J=6.6,1.4Hz,1H),6.01(m,1H),2.13(s,3H),1.43(s,9H). 13 C NMR (101MHz, CDCl3) δ168.32,162.23,151.49,136.02,135.62,134.88,128.74,12 6.76,122.20,118.77,108.44,83.08,59.72,27.99,21.35.HRMS(ESI):calculated for C 20 H 23 NO3Na[M+Na]+:348.1570; Found:348.1569.

[0136] Example 26

[0137]

[0138] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2e 91.8 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ea 56.5 mg, yield 87%; mp: 162-163 °C. 1 H NMR(400MHz,Chloroform-d)δ7.44-7.39(m,2H),7.38-7.29(m,3H),7.22(dd,J=9.2,2.5Hz,1H),7.17-7.15(m,1H),6.64(dd,J =16.1,1.4Hz,1H),6.56(d,J=9.3Hz,1H),6.40(dd,J=16.0,6.8Hz,1H),6.13(dd,J=6.8,1.5Hz,1H),2.08(s,3H),1.50(s,9H). 13C NMR (101MHz, CDCl3) δ168.30,161.58,142.49,136.13,135.64,133.22,128.75,128.63 ,126.79,122.22,120.05,114.80,83.07,60.15,28.00,17.36.HRMS(ESI):calculated for C 20 H 23 NO3Na[M+Na]+:348.1570; Found:348.1568.

[0139] Example 27

[0140]

[0141] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2f 109.6 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3fa 63.0 mg, yield 81%; mp: 150-151 °C. 1 H NMR(400MHz,Chloroform-d)δ7.52(m,1H),7.43(m,2H),7.39(m,1H),7.37-7.33(m,3H),6.69(dd,J=1 6.1,1.4Hz,1H),6.53(m,1H),6.34(dd,J=16.0,7.0Hz,1H),6.03(dd,J=7.0,1.5Hz,1H),1.51(s,9H). 13 C NMR (101MHz, CDCl3) δ167.69,160.78,142.97,137.41,135.94,135.22,129.00,12 8.86,126.93,121.59,120.96,98.10,83.58,60.68,27.99.HRMS(ESI):calculated for C 19 H 20 BrNO3Na[M+Na]+:412.0519; Found:412.0520

[0142] Example 28

[0143]

[0144] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridine-2-one derivative 2 g 105.2 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ga 63.0 mg, yield 89%; mp: 110-111 °C. 1 H NMR(400MHz,Chloroform-d)δ7.81(m,1H),7.48(m,1H),7.43(m,2H),7.40-7.33(m,3H),6.75-6.69(dd,J=16.0,7. 1Hz, 1H), 6.68-6.65 (d, J=16.0, 9.6Hz, 1H), 6.35 (dd, J=16.0, 7.1Hz, 1H), 6.06 (dd, J=7.1, 1.4Hz, 1H), 1.51 (s, 9H). 13 C NMR (101MHz, CDCl3) δ167.47,161.58,137.83,135.79,135.74,135.37,135.36,135.10,13 5.10,129.10,128.88,126.95,121.02,120.50,83.80,77.38,77.07,76.75,60.83,27.96.

[0145] 19F NMR (282MHz, CDCl3): δ (ppm)-62.37

[0146] HRMS(ESI): calculated for C 20 H 20 F3NO3Na[M+Na]+:402.1287; Found:402.1286.

[0147] Example 29

[0148]

[0149] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2i 70.5 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ia 32.8 mg, yield 58%; mp: 128-129 °C. 1 H NMR(400MHz,Chloroform-d)δ7.42(m,3H),7.39-7.36(m,1H),7.36-7.32(m,2H),7.32-7.29(m,1H),6.65(dd,J=16.0,1.3Hz,1H),6.61(dd,J=9.2,1 .3Hz,1H),6.43(dd,J=16.0,7.0Hz,1H),6.23(td,J=6.8,1.5Hz,1H),6.15 (dd, J=7.1, 1.3Hz, 1H), 4.29 (qd, J=7.3, 2.0Hz, 2H), 1.31 (t, J=7.2Hz, 3H). 13 C NMR(101MHz, CDCl3)δ169.05,162.26,139.91,136.85,135.92,135.37,128.78,126.86,121.32,120.58,106.11,62.21,60.24,14.15.HRMS(ESI): calculated for C 17 H 17 NO3Na[M+Na]+:306.1100; Found:306.1100.

[0150] Example 30

[0151]

[0152] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2j 91.7 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3ja 38.6 mg, yield 56%. 1 HNMR(400MHz,Chloroform-d)δ7.35-7.29(m,2H),7.28(m,4H),7.25(m,2H),7.24(m,3H),7.23-7.19(m,2H),6.59-6.51(m,1H),6.48(d d,J=16.0,1.3Hz,1H),6.32(dd,J=16.0,6.9Hz,1H),6.13(dd,J=6.8,5.3Hz,2H),5.22(d,J=12.3Hz,1H),5.18-5.12(d,J=12.3Hz,1H). 13 C NMR (101MHz, CDCl3) δ168.95,162.30,139.98,137.09,135.85,128.94,128.85,128.77,128.66, 128.51,128.40,128.19,126.86,120.99,120.59,106.16,67.72,60.18.HRMS(ESI):calculated for C 22 H 19 NO3Na[M+Na]+:368.1256; Found:368.1256.

[0153] Example 31

[0154]

[0155] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2k 54.8 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid of 3 kJ 38.6 mg, yield 56%.1 HNMR(400MHz,Chloroform-d)δ7.47(m,1H),7.34(m,2H),7.29(mz,2H),7.25-7.18(m,2H),7.02( d,J=16.0Hz,1H),6.71(m,1H),6.30(td,J=6.7,1.4Hz,1H),6.02(d,J=16.1Hz,1H),2.32(s,3H). 13 C NMR (101MHz, CDCl3) δ168.95,162.30,139.98,137.09,135.85,128.94,128.85,128.77,128.66, 128.51,128.40,128.19,126.86,120.99,120.59,106.16,67.72,60.18.HRMS(ESI):calculated for C 16 H 16 NO2[M+H]+:254.1176Found:254.1173

[0156] Example 32

[0157]

[0158] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2l 71.7 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol) were added sequentially to the reaction tube, followed by catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF. The reaction was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3la 23.6 mg, yield 40%. 1 HNMR(400MHz,Chloroform-d)δ7.48-7.41(m,2H),7.40-7.33(m,4H),6.76(d,J=15.9Hz,1H),6.60(dd,J=9.7,1.3Hz,1H),6.33(dd,J=15.9,8.5 Hz,1H),6.23(td,J=6.8,1.3Hz,1H),6.06(d,J=8.5Hz,1H),2.82-2.63(m,2H),1.69-1.60(m,2H),1.34(q,J=7.4Hz,2H),0.90(t,J=7.3Hz,3H). 13C NMR (101MHz, CDCl3) δ205.09,162.30,139.91,139.16,135.68,135.22,129.11,128.88,12 6.89,120.37,120.33,106.03,66.10,40.73,25.48,22.24,13.86.HRMS(ESI):calculated for C 19 H 21 NO2Na[M+Na]+:318.1465; Found:318.1463

[0159] Example 33

[0160]

[0161] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2m 79.6 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 5] to give a white solid 3mA 42.8 mg, yield 68%. 1 HNMR(400MHz,Chloroform-d)δ8.13(m,2H),7.60(m,1H),7.50(m,4H),7.41-7.37(m,3H),7.33(m,3H ), 6.70 (d, J = 16.2Hz, 1H), 6.62 (d, J = 9.2Hz, 1H), 6.45 (dd, J = 16.1, 7.5Hz, 1H), 6.26 (t, J = 6.8Hz, 1H). 13 C NMR (101MHz, CDCl3) δ195.37,162.18,139.98,138.82,136.00,135.30,135.06,134.01,129. 02,129.00,128.94,128.82,126.88,121.67,120.29,106.15,60.41.HRMS(ESI):calculated for C 21 H 18 NO2[M+H]+:316.1332Found:316.1332.

[0162] Example 34

[0163]

[0164] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridine-2-one derivative 2o 83.3 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2(esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h, and no product spot was formed.

[0165] Example 35

[0166]

[0167] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridine-2-one derivative 2p 85.3 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2(esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h, and no product spot was formed.

[0168] Example 36

[0169]

[0170] Sulfonylhydrazone derivative 1a 66.2 mg (0.2 mmol), pyridin-2-one derivative 2n 79.6 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 3] to give a yellow solid 3na 45.2 mg, yield 73%. 1HNMR(400MHz,Chloroform-d)δ7.62(m,1H),7.43-7.39(m,2H),7.34(m,4H),6.74- 6.68(m,2H),6.56(m,1H),6.36(dd,J=16.4,6.2Hz,1H),6.20(td,J=6.8,1.5Hz,1H ),3.59(dq,J=14.2,7.1Hz,1H),3.52(dd,J=7.2,2.7Hz,1H),3.49(dd,J=7.2,2.6H z,1H),3.31(dq,J=14.1,7.1Hz,1H),1.31(t,J=7.2Hz,3H),1.18(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ167.32,162.34,139.95,136.94,136.89,135.41,128.85,128.82,12 6.85,122.87,119.70,105.86,55.30,42.36,41.10,14.29,12.94.HRMS(ESI):calculated forC 19 H 22 N2O2Na[M+Na]+:333.1573; Found:333.1569

[0171] Example 37

[0172]

[0173] The template substrate 3aa 62.3 mg (0.2 mmol), Pd / C 6.23 mg (10 wt%), and 3 mL of methanol were added sequentially to the reaction tube. The tube was sealed and filled with a hydrogen balloon for the reaction. The reaction was carried out at 25 °C for 2 h. After the reaction was completed, the diatomaceous earth was filtered, and the solvent was evaporated to give 462.5 mg of white solid, yield 99%, mp: 144-146 °C. 1 H NMR(400MHz,Chloroform-d)δ7.36-7.32(m,1H),7.32-7.27(m,3H),7.22-7.20(m,1H),7.17-7.13(m,2H),6.59(dt,J=9.0,1.0Hz,1H),6.22( td,J=6.8,1.4Hz,1H),5.52(dd,J=10.0,5.0Hz,1H),2.71-2.61(m,1H) ,2.61-2.52(m,1H),2.52-2.43(m,1H),2.25-2.14(m,1H),1.45(s,9H). 13C NMR (101MHz, CDCl3) δ169.4,162.6,140.4,139.4,135.4,128.6,128.4,126.4,120.7,106.0,82.7,57.8,33.0,32.2,28.0.HRMS(ESI): calculated for C 19 H 23 NO3[M+H]+:314.1751Found:314.1750.

[0174] Example 38

[0175]

[0176] 1. Sulfonylhydrazone derivative 10.98 mg (0.2 mmol), pyridine-2-one derivative 20.796 mg (0.4 mmol), sodium hydride 12 mg (0.3 mmol), and catalyst Rh2 (esp) 21.6 mg (0.002 mmol) and 4 mL THF were added sequentially to the reaction tube. The tube was sealed and purged with argon gas. The reaction was carried out at 40 °C for 10 h. After the reaction, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 3] to obtain 539 mg of a transparent oil, yield 50%. HPLC detection: 0% ee; HPLC conditions: Daicel Chiralpak IA column, n-hexane / i-PrOH = 80 / 20, flow rate 2.0 mL / min, λ = 215 nm, t R = 19.66min and 33.32min

[0177] 2. Add 10.98 mg (0.2 mmol) of sulfonylhydrazone derivative, 279.6 mg (0.4 mmol) of pyridin-2-one derivative, and 12 mg (0.3 mmol) of sodium hydride sequentially to the reaction tube. Then add 43.6 mg (0.002 mmol) of catalyst Rh2 (s-TBPTTL) and 4 mL of 2-MeTHF. Seal the tube and purge with argon gas. The reaction is carried out at -10 °C for 10 h. After the reaction, the solvent is removed by vacuum distillation. The product is purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 3] to obtain 519.5 mg of a transparent oil, yield 25%. 11H NMR (400 MHz, Chloroform-d) δ 7.95–7.90 (m, 2H), 7.77–7.68 (m, 3H), 7.49–7.41 (m, 4H), 7.40–7.34 (m, 4H), 7.34–7.27 (m, 4H), 6.49 (dd, J = 9.1, 1.4 Hz, 1H), 6.28 (td, J = 6.8, 1.4 Hz, 1H). 13 13C NMR (101 MHz, CDCl3) δ 188.66, 161.93, 140.06, 135.93, 135.06, 134.87, 131.88, 131.78, 129.48, 129.28, 129.16, 128.76, 128.74, 128.47, 127.89, 106.95, 92.88, 85.73, 72.06. HPLC detection: 89% ee; HPLC conditions: Daicel Chiralpak IA column, n-hexane / i-PrOH = 80 / 20, flow rate 2.0 mL / min, λ = 215 nm, t R = 18.98 min (minor) and 32.17 min (major).

Claims

1. A method for synthesizing an N-alkylated pyridin-2-one derivative, characterized in that: Using sulfonylhydrazone derivative 1o and pyridin-2-one derivative 2m as raw materials, under the catalysis of Rh2(S-TBPTTL)4, with the addition of an alkaline additive, at -10℃, an enantioselective N-alkylated pyridin-2-one derivative of formula (1) was synthesized. ； ； 。 2. The method for synthesizing the N-alkylated pyridin-2-one derivative as described in claim 1, characterized in that: The reaction was first carried out by adding sulfonylhydrazone derivative 1o, pyridine-2-one derivative 2m and Rh2(S-TBPTTL)4 catalyst, adding base additive, adding solvent, and protecting with argon gas. The reaction was stirred at -10℃. After the reaction was completed, the solvent was removed by vacuum distillation, and the target product of N-alkylated pyridine-2-one derivative was obtained by column chromatography or recrystallization.

3. The method for synthesizing the N-alkylated pyridin-2-one derivative as described in claim 1, characterized in that: The amount of pyridine-2-one derivative used is 0.5-2.0 equivalents of the amount of sulfonylhydrazone derivative used.

4. The method for synthesizing the N-alkylated pyridin-2-one derivative as described in claim 1, characterized in that: The amount of rhodium catalyst used is 0.5-2.5% of the molar amount of the sulfonylhydrazone derivative.

5. The method for synthesizing the N-alkylated pyridin-2-one derivative as described in claim 1, characterized in that: The solvent used is one of dichloromethane, n-hexane, acetonitrile, diethyl ether, chloroform, toluene, tetrahydrofuran, or 1,2-dichloroethane, and the concentration of the sulfonylhydrazone derivative in the solvent is 0.05-0.2 mol / L.

6. The method for synthesizing the N-alkylated pyridin-2-one derivative as described in claim 1, characterized in that: The alkali additive used is LiO t One of Bu, DIPEA, Et3N, DBU, DABCO, DMAP, and NaH is used in an amount of 0.5-2.5 equivalents of the amount of the sulfonylhydrazone derivative.

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