Preparation method for synthesizing amide compound through photochemical driving

Abstract

The invention discloses a preparation method for synthesizing an amide compound through photochemical driving, which comprises the following steps of: reacting a compound 1 as a raw material in acetonitrile under illumination for time t, and reacting through a dichloromethane system of iodine, triphenylphosphine and triethylamine to obtain a product 1; according to the method, the reaction conditions are relatively mild, and photochemical driving is utilized, so that the energy consumption and harsh condition requirements of the traditional thermal reaction are reduced; precise conversion of a compound with a specific alpha-aminoketone structure can be realized, a new path is provided for synthesis and modification of amide compounds, and preparation methods of the amide compounds in organic synthesis and related application fields are expanded.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and more specifically, relates to a method for preparing amide compounds through photochemical-driven synthesis. Background Technology

[0002] Amide compounds are a very important class of organic compounds. As crucial intermediates in organic synthesis, they are widely found in the molecular structures of drugs, natural products, and functional materials, and have broad applications in fields such as medicine. However, traditional methods for synthesizing amides involve thermal reactions, resulting in high energy consumption and demanding reaction conditions, which limits the further application of amide compounds. Therefore, developing a new, efficient, and universal method for synthesizing amides is of great significance for the development of organic synthetic chemistry and its applications in drug molecule modification. Summary of the Invention

[0003] To address the aforementioned deficiencies or improvement needs of existing technologies, this invention provides a photochemical-driven method for preparing amide compounds. It proposes a synthetic route that utilizes photochemical driving to reduce the energy consumption and stringent conditions required by traditional thermal reactions. This method enables the precise conversion of compounds with specific α-aminoketone structures, providing a new pathway for the synthesis and modification of amide compounds and expanding the preparation methods for amide compounds in organic synthesis and related applications.

[0004] To achieve the above objectives, in one embodiment of the present invention, the present invention provides a method for preparing a photochemically driven synthesis of an amide compound, using compound 1 of general formula as a raw material, reacting it in acetonitrile under light irradiation for time t, and then reacting it in a dichloromethane system of iodine, triphenylphosphine, and triethylamine to obtain product 1;

[0005] The general reaction formula is as follows:

[0006]

[0007] Among them, R 1 It is selected from hydrogen, halogen, alkyl with 1 to 12 carbon atoms, alkoxy with 1 to 12 carbon atoms, cycloalkyl with 3 to 12 carbon atoms, halogen-substituted alkyl with 1 to 6 carbon atoms, halogen-substituted alkoxy with 1 to 6 carbon atoms, halogen-substituted cycloalkyl with 1 to 6 carbon atoms, aryl with 6 to 30 carbon atoms, and heteroaryl with 3 to 30 carbon atoms;

[0008] R 2 Selected from alkyl groups having 3 to 12 carbon atoms and cycloalkyl groups having 3 to 12 carbon atoms;

[0009] R 3 It is selected from alkyl groups having 1 to 12 carbon atoms and aryl groups having 6 to 30 carbon atoms;

[0010] R 4 Selected from furanyl, thiopheneyl, aryl groups with 6 to 30 carbon atoms, and heteroaryl groups with 6 to 30 carbon atoms;

[0011] If compound 1 is in the form of a hydrochloride salt, then the raw material needs to be added with a strong base in a molar ratio of 1:1 to compound 1;

[0012] The molar ratio of the general formula compound 1, iodine, triphenylphosphine, and triethylamine is 1:1-10:1-10:1.6-16; (wherein, the amount of triethylamine is always slightly higher than the amount of general formula compound 1, iodine, and triphenylphosphine).

[0013] The solvent is selected from at least one or a mixture of multiples of acetonitrile, chloroform, 1,2-dichloroethane, diethyl ether, and tetrahydrofuran;

[0014] The light used for illumination is selected from the visible light region.

[0015] In an optional embodiment of the invention, the R 2 It is selected from secondary alkyl groups, tertiary alkyl groups, and cycloalkyl groups with 3 to 12 carbon atoms.

[0016] In an optional embodiment of the invention, the R 2 For tert-butyl;

[0017] The R 3 It is selected from alkyl groups having 1 to 12 carbon atoms and aryl groups having 6 to 30 carbon atoms;

[0018] In an optional embodiment of the invention, the R 3 It is methyl;

[0019] The R 2 It is selected from secondary alkyl groups, tertiary alkyl groups, cyclopentyl groups, and cyclohexyl groups with 3 to 12 carbon atoms.

[0020] In an optional embodiment of the invention, the R 4 Selected from furanyl, thiopheneyl, and arylene groups with 6 to 30 carbon atoms;

[0021] R 1 It is selected from hydrogen, halogen, alkyl with 1 to 12 carbon atoms, alkoxy with 1 to 12 carbon atoms, cycloalkyl with 3 to 12 carbon atoms, halogen-substituted alkyl with 1 to 6 carbon atoms, halogen-substituted alkoxy with 1 to 6 carbon atoms, halogen-substituted cycloalkyl with 1 to 6 carbon atoms, aryl with 6 to 30 carbon atoms, and heteroaryl with 3 to 30 carbon atoms.

[0022] Preferably, in an optional embodiment of the present invention, the R 4 Selected from furanyl, thiopheneyl, and phenylene.

[0023] In an optional embodiment of the invention, the wavelength range of the illumination is 385–400 nm.

[0024] In an optional embodiment of the present invention, the reaction time t is selected from 12 to 30 hours.

[0025] In an optional embodiment of the present invention, the solvent is selected from at least one of acetonitrile, chloroform, 1,2-dichloroethane, diethyl ether, and tetrahydrofuran.

[0026] In an optional embodiment of the present invention, the solvent is selected from any one of acetonitrile, chloroform, 1,2-dichloroethane, diethyl ether, and tetrahydrofuran. Preferably, the solvent is acetonitrile.

[0027] In an optional embodiment of the present invention, the molar ratio of the general formula compound 1, iodine, triphenylphosphine, and triethylamine is 1:1:1:1.6.

[0028] Furthermore, in an optional embodiment of the present invention, a synthetic route is proposed for preparing compound 3 as shown:

[0029]

[0030] In step (1) of the above reaction, compound 2 (and sodium hydroxide if compound 2 is in hydrochloride form) and solvent are added to the reaction flask. The reaction system is then placed at room temperature (preferably 25°C) and stirred in a 385–400 nm light-irradiated reaction module for 12–30 hours to obtain the intermediate product.

[0031] In step (2) of the above reaction, under normal temperature conditions, a dichloromethane solution of iodine and triphenylphosphine is added to the above intermediate product system. The reaction system is placed at room temperature (preferably 25°C), and after stirring for 5 minutes in a parallel reaction module, triethylamine is added. The reaction endpoint is detected by TLC, and the target compound 3 is directly obtained by column chromatography with a volume ratio of petroleum ether to ethyl acetate of 50:1 to 3:1.

[0032] Furthermore, in an optional embodiment of the present invention, a method for synthesizing amides using 2-(tert-butylamino)-1-phenylethane-1-one hydrochloride as a raw material is provided:

[0033]

[0034] (1) Add compound 4, solvent and sodium hydroxide to the reaction flask, place the reaction system under 385–400 nm light irradiation and stir at room temperature for 12 hours to obtain intermediate product;

[0035] (2) Under normal temperature conditions, add a dichloromethane solution of iodine and triphenylphosphine to the above intermediate product system, stir the reaction at room temperature for 5 minutes, add triethylamine, place the reaction system at room temperature and stir the reaction, detect the reaction endpoint by TLC, and obtain the target compound 5 by separation and purification of the reaction system.

[0036] The molar ratio of compound 4 and sodium hydroxide shown in step (1) is 1:1.

[0037] The feeding sequence of step (1) of the present invention is the compound shown in Formula I, sodium hydroxide, and solvent.

[0038] The feeding sequence in step (2) is to add a dichloromethane solution of iodine and triphenylphosphine to the intermediate product system after the reaction in step (1), stir the reaction at room temperature for five minutes, and then add triethylamine.

[0039] The solvents used in this invention include acetonitrile, chloroform, 1,2-dichloroethane, diethyl ether, and tetrahydrofuran. Acetonitrile is preferred. If the organic solvent of the reaction system is chloroform, 1,2-dichloroethane, diethyl ether, or tetrahydrofuran, under the same other reaction conditions, the yield of compound 5 shown is slightly lower than that of the acetonitrile solution system.

[0040] The molar ratio of compound 4, iodine, triphenylphosphine, and triethylamine in step (2) is 1:1:1:1.6.

[0041] In this invention, the separation and purification of target compound 5 includes: silica gel column chromatography separation and purification of the compound represented by formula II, wherein a mixture of petroleum ether and ethyl acetate is used as the separating phase, and the volume ratio of petroleum ether to ethyl acetate is 50:1 to 10:1.

[0042] Furthermore, in an optional embodiment of the present invention, a method for synthesizing amides using α-aminoarylacetone compounds as raw materials is provided:

[0043] (1) Add compound 6 and solvent as shown to the reaction flask, and stir the reaction system at room temperature under 385–400 nm light for 12–30 hours to obtain the intermediate product.

[0044] (2) Under normal temperature conditions, add a dichloromethane solution of iodine and triphenylphosphine to the above intermediate product system, stir the reaction at room temperature for 5 minutes, add triethylamine, place the reaction system at room temperature and stir the reaction, detect the reaction endpoint by TLC, and obtain the target compound 7 by separation and purification of the reaction system.

[0045] The molar ratio of compound 6, iodine, triphenylphosphine, and triethylamine in step (2) is 1:1:1:1.6.

[0046] The general reaction formula is:

[0047]

[0048] R1 is selected from hydrogen, methyl, methoxy or halogen, and R1 can also be selected from derivative structures of drug molecules such as ibuprofen and naproxen; R2 is selected from secondary alkanes and tertiary alkanes.

[0049] In embodiments of the present invention, the structures of amide derivatives can be obtained, including but not limited to:

[0050]

[0051]

[0052] The feeding sequence in step (2) is as follows: add a dichloromethane solution of iodine and triphenylphosphine to the intermediate product system after the reaction in step (1), stir the reaction at room temperature for five minutes, and then add triethylamine.

[0053] In this invention, the separation and purification of the target compound 7 includes: silica gel column chromatography separation and purification of the compound 7, wherein a mixture of petroleum ether and ethyl acetate is used as the separating phase, and the volume ratio of petroleum ether to ethyl acetate is 50:1 to 3:1.

[0054] Furthermore, in an optional embodiment of the present invention, a method for synthesizing amides using α-tert-butylamine aromatic ketone compounds as raw materials is provided, the reaction steps of which are the same as those in the above embodiments, and the general reaction formula is:

[0055]

[0056] R1 is selected from hydrogen, methyl, sulfonyl, etc., and the position of R1 is not fixed; R3 is selected from propyl, butyl, phenylethyl, phenylpropyl.

[0057] In embodiments of the present invention, amide derivatives can be obtained, including but not limited to:

[0058]

[0059] In summary, compared with the prior art, the above-described technical solutions conceived by this invention can achieve the following beneficial effects:

[0060] 1. The method for preparing amide compounds of the present invention proposes a synthetic route, providing a new, efficient and convenient method for the synthesis of amide compounds. The method of the present invention has relatively mild reaction conditions and utilizes photochemical driving, reducing the energy consumption and harsh conditions required by traditional thermal reactions.

[0061] 2. The preparation method of the amide compounds of the present invention can achieve precise conversion of specific α-aminoketone structures, providing a new route for the synthesis and modification of amide compounds, and expanding the preparation methods of amide compounds in organic synthesis and related application fields.

[0062] 3. The method for preparing amide compounds of the present invention has a certain degree of substrate applicability, and can effectively convert various α-amino ketone structures containing different substituents (such as alkyl, alkoxy, halogen, trifluoromethyl, etc.). At the same time, it can use drug molecules such as ibuprofen, naproxen, gemfibrozil, probenecid, etc. as starting materials to achieve derivatization through reaction, expand the diversity of drug molecule structures, and provide technical support for the subsequent synthesis of drug intermediates, functional material precursors, etc. Attached Figure Description

[0063] Figure 1 For compound II-1 in CDCl3 1 H NMR.

[0064] Figure 2 For compound II-1 in CDCl3 13 C NMR.

[0065] Figure 3 Compound II-25 in CDCl3 1 H NMR.

[0066] Figure 4 Compound II-25 in CDCl3 13 C NMR.

[0067] Figure 5 For compound II-26 in CDCl3 1 H NMR.

[0068] Figure 6 For compound II-26 in CDCl3 13 C NMR.

[0069] Figure 7 For compound II-27 in CDCl3 1 H NMR.

[0070] Figure 8 For compound II-27 in CDCl3 13 C NMR.

[0071] Figure 9 For compound II-28 in CDCl3 1 H NMR.

[0072] Figure 10 For compound II-28 in CDCl3 13 C NMR. Detailed Implementation

[0073] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0074] Throughout this specification, unless otherwise specified, the terminology used herein should be understood as having the meaning commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In the event of any conflict, this specification shall prevail.

[0075] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0076] Unless otherwise specified, all materials, reagents, instruments, etc. used in the following examples are commercially available.

[0077] In the embodiments of the present invention, unless otherwise specified, the melting points of the compounds in the following reactions are determined using a melting point apparatus, the NMR spectra are determined using a 400 MHz or 600 MHz NMR spectrometer, the tests are performed using deuterated chloroform or deuterated dimethyl sulfoxide as solvents, the HRMS mass spectrometry is performed on a mass spectrometer, and the infrared spectrometry is performed on an FTIR-650.

[0078] In the embodiments of the present invention, unless otherwise specified, "room temperature" and "normal temperature" should be regarded as conventional temperatures between 20 and 30 degrees Celsius, that is, the reaction described in the embodiments of the present invention can proceed normally at this temperature without additional heating.

[0079] In the embodiments of the present invention, unless otherwise specified, the separation and purification of the products are carried out by column chromatography, wherein a mixture of petroleum ether and ethyl acetate is used as the separating phase, and the volume ratio of petroleum ether to ethyl acetate is 50:1 to 3:1.

[0080] As used in this invention, the term "halogen group" may include fluorine, chlorine, bromine or iodine.

[0081] As used in this invention, the term "C1-C12 alkyl" refers to a monovalent substituent derived from a straight-chain or branched saturated hydrocarbon having 1 to 12 carbon atoms, examples of which include, but are not limited to, methyl, ethyl, propyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, and hexyl.

[0082] As used herein, the term "C3-C12 cycloalkyl" refers to a monovalent substituent derived from a monocyclic or polycyclic nonaromatic hydrocarbon having 3 to 12 carbon atoms. Examples of such cycloalkyl groups include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclohexane, norbornyl, adamantane, etc.

[0083] As used herein, the term "alkoxy" refers to a straight-chain, branched, or cyclic chain. The number of carbon atoms in an alkoxy group is not particularly limited, but it is preferred to have 1 to 12 carbon atoms. Specific examples include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, i-propyloxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentoxy, neopentoxy, isopentoxy, n-hexyloxy, and benzyloxy.

[0084] As used herein, the term "C6-C30 aryl" refers to a monovalent substituent derived from an aromatic hydrocarbon having a single ring or a combination of two or more rings and having 6 to 30 carbon atoms. Further, such an aryl group may have two or more rings simply side-attached to or fused together with each other. Examples of such aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, phenanthryl, anthracene, pyrene, triphenylene, fluoranthyl, dimethyl-9,9-dimethylfluorene, 9,9-diphenylfluorene, spirodifluorene, etc.

[0085] As used in this invention, the term "arylene" refers to a divalent aryl group derived by removing one hydrogen atom from an "aryl" group, for example, a phenyl group by removing one hydrogen atom to form a phenylene group, and a naphthyl group by removing one hydrogen atom to form a naphthylene group.

[0086] As used in this invention, the term "C3-C30 heteroaryl" refers to a monovalent substituent derived from a monoheterocyclic or polyheterocyclic aromatic hydrocarbon having 3 to 30 carbon atoms. In this connection, at least one carbon in the ring, preferably 1 to 3 carbons, is substituted with a heteroatom, such as N, O, S, P, B, or Si. Furthermore, such a heteroaryl can have a form in which two or more rings are simply side-attached to each other, fused together, or fused with an aryl group. Examples of such heteroaryl groups include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, indoleazinyl, indoleyl, indolepyridinyl, purineyl, phenanthrolinel, quinolinyl, isoquinolinyl, quinazolinyl, quinoxolinyl, thiazolyl, imidazolyl, oxazolyl, furanyl, thiophene, benzofuranyl, benzothiophene, benzothiazolyl, benzoimidazolyl, benzooxazolyl, carbazole, dibenzofuranyl, dibenzothiophene, etc., but the present invention is not limited thereto.

[0087] As used in this invention, the term "hybrid aryl" refers to a divalent heteroaryl derived by removing a hydrogen atom from a "heteroaryl", for example, a pyridyl group by removing a hydrogen atom to form a pyridyl group.

[0088] As used in this invention, the term "heterocyclic group" refers to a saturated heterocyclic group or an unsaturated heterocycle containing heteroatoms.

[0089] As used in this invention, the expression "Z group with XY carbon atoms" or "Z group with C(XY)" means the number of carbon atoms in the Z group when it is unsubstituted, excluding the number of carbon atoms in the substituents when substituted. For example, an aryl group with C6-C60 means that when unsubstituted, the number of carbon atoms in the aryl group is any integer from 6 to 60. That is, when unsubstituted, the number of carbon atoms can be 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20...60.

[0090] Effect of the solvent used in the preparation of Example 1 on the reaction

[0091]

[0092] 2-(tert-butylamino)-1-phenylethane-1-one hydrochloride (0.5 mmol, 1.0 eq.), sodium hydroxide (0.5 mmol, 1.0 eq.), and solvent (2.5 mL) were added sequentially to a reaction flask. The reaction system was placed under light at a wavelength of 385–400 nm and stirred at room temperature for 12 hours to obtain an intermediate product. A dichloromethane solution of iodine and triphenylphosphine was added to the above intermediate product system, and the mixture was stirred at room temperature for 5 minutes. Triethylamine was then added, and the reaction system was stirred at room temperature. The reaction endpoint was detected by TLC (thin-layer chromatography). The reaction system was separated and purified to obtain the target compound represented by Formula II. The solvents used and the yields are shown in Table 1 below.

[0093] Table 1 Effect of solvent on reaction yield

[0094]

[0095] In the photocatalytically induced reaction of the present invention, the solvents used include acetonitrile, chloroform, 1,2-dichloroethane, diethyl ether, and tetrahydrofuran. Acetonitrile is preferred. If the organic solvent of the reaction system is chloroform, 1,2-dichloroethane, diethyl ether, or tetrahydrofuran, the yield of the compound shown in Formula II is slightly lower than that of the acetonitrile solution system, under the same other reaction conditions.

[0096] Example 2: Synthesis of amide compound II-1 using compounds containing an α-aminoketone structure

[0097] 2-(tert-butylamino)-1-phenylprop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 72%.

[0098] Detection via proton and carbon NMR spectra (e.g.) Figure 1 and Figure 2 As shown in the figure, the obtained product is the target compound II-1. The 1H and 1C NMR spectra of compound II-1 are as follows:

[0099] 1 H NMR (400MHz, CDCl3) δ7.71 (d, J = 7.0Hz, 2H), 7.46 (t, J = 7.3Hz, 1H), 7.40 (t, J = 7.3Hz, 2H), 5.97 (s, 1H), 1.47 (s, 9H);

[0100] 13 C NMR (101MHz, CDCl3) δ167.1,136.0,131.2,128.6,126.8,51.7,29.0.

[0101] Example 3: Synthesis of amide compound II-1 using hydrochloride containing an α-aminoketone structure

[0102] 2-(tert-butylamino)-1-phenylethane-1-one hydrochloride (0.5 mmol, 1.0 eq.), sodium hydroxide (0.5 mmol, 1.0 eq.), and acetonitrile (2.5 mL) were added sequentially to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product was obtained by separation and purification, and was a white solid with a yield of 56%.

[0103] Example 4 Synthesis of amide compound II-2

[0104]

[0105] 2-(tert-butylamino)-1-(2-methoxyphenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 41%.

[0106] The product obtained by detection using 1H and 1C NMR spectra was the target compound II-2. The 1H and 1C NMR spectra of compound II-2 are as follows:

[0107] 1 H NMR (400MHz, CDCl3) δ8.16(d,J=7.9Hz,1H),7.83(s,1H),7.50–7.33(m,1H),7.04(t,J=7.5Hz,1H),6.93(d,J=8.4Hz,1H),3.92(s,3H),1.45(s,9H);

[0108] 13 C NMR (101 MHz, CDCl3) δ 164.3, 157.3, 132.4, 132.0, 122.8, 121.4, 111.4, 56.0, 51.1, 29.0. Example 5: Synthesis of amide compound II-3

[0109]

[0110] 2-(tert-butylamino)-1-(3-methoxyphenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 19 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 59%.

[0111] The product obtained by detection using 1H and 1C NMR spectra was the target compound II-3. The 1H and 1C NMR spectra of compound II-3 are as follows:

[0112] 1 H NMR (400MHz, CDCl3) δ7.32(s,1H),7.30(t,J=7.8Hz,1H),7.21(d,J=7.7Hz,1H),7.00(d,J=8.2Hz,1H),5.96(s,1H),3.84(s,3H),1.46(s,9H);

[0113] 13 C NMR (101MHz, CDCl3) δ166.8,159.9,137.5,129.5,118.5,117.5,112.3,55.6,51.8,29.0.

[0114] Example 6 Synthesis of amide compound II-4

[0115]

[0116] 2-(tert-butylamino)-1-(4-methoxyphenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 68%.

[0117] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-4. The 1H and 1C NMR spectra are shown below:

[0118] 1 H NMR (400MHz, CDCl3) δ7.68 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 5.86 (s, 1H), 3.84 (s, 3H), 1.46 (s, 9H);

[0119] 13 C NMR (151MHz, CDCl3) δ166.6,162.0,128.6,128.3,113.7,55.5,51.6,29.1.

[0120] Example 7 Synthesis of amide compound II-5

[0121]

[0122] 2-(tert-butylamino)-1-(m-tolyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 59%.

[0123] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-5. The 1H and 1C NMR spectra are shown below:

[0124] 1 H NMR (400MHz, CDCl3) δ7.47 (s, 1H), 7.41 (d, J = 6.2Hz, 1H), 7.24–7.16 (m, 2H), 5.87 (s, 1H), 2.31 (s, 3H), 1.40 (s, 9H);

[0125] 13 C NMR (101MHz, CDCl3) δ167.2,138.4,136.0,131.9,128.4,127.6,123.8,51.7,29.0,21.5.

[0126] Example 8 Synthesis of amide compound II-6

[0127]

[0128] 2-(tert-butylamino)-1-(p-tolyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 48%.

[0129] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-6. The 1H and 1C NMR spectra are shown below:

[0130] 1 H NMR (400MHz, CDCl3) δ7.61 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 7.9 Hz, 2H), 5.93 (s, 1H), 2.37 (s, 3H), 1.46 (s, 9H);

[0131] 13 C NMR (101MHz, CDCl3) δ167.1,141.5,133.1,129.2,126.8,51.7,29.0,21.5.

[0132] Example 9 Synthesis of amide compound II-7

[0133]

[0134] 2-(tert-butylamino)-1-(4-ethylphenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 52%.

[0135] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-7. The 1H and 1C NMR spectra are shown below:

[0136] 1 H NMR (400MHz, CDCl3) δ7.64(d,J=8.2Hz,2H),7.22(d,J=8.0Hz,2H),5.96(s,1H),2.67(q,J=7.6Hz,2H),1.46(s,9H),1.23(t,J=7.6Hz,3H);

[0137] 13 C NMR (101MHz, CDCl3) δ167.1,147.8,133.3,128.0,126.9,51.6,29.0,28.8,15.5.

[0138] Example 10 Synthesis of amide compound II-8

[0139]

[0140] 2-(tert-butylamino)-1-(3-fluorophenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 44%.

[0141] The product obtained by detection using 1H NMR, 1C NMR, and fluorine NMR spectra was identified as the target compound II-8. The 1H NMR, 1C NMR, and fluorine NMR spectra are shown below:

[0142] 1 H NMR (400MHz, CDCl3) δ7.48–7.40(m,2H),7.40–7.33(m,1H),7.19–7.11(m,1H),5.95(s,1H),1.46(s,9H);

[0143] 13 C NMR (101MHz, CDCl3) δ165.7 (d, J = 2.5Hz), 162.9 (d, J = 247.4Hz), 138.4 (d, J = 6.6Hz), 130. 2(d,J=7.8Hz),122.3(d,J=3.1Hz),118.2(d,J=21.3Hz),114.3(d,J=22.7Hz),52.0,28.9;

[0144] 19 F NMR (376MHz, CDCl3) δ-112.1.

[0145] Example 11 Synthesis of amide compound II-9

[0146]

[0147] 2-(tert-butylamino)-1-(4-fluorophenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 68%.

[0148] The product obtained by detection using 1H NMR, 1C NMR, and fluorine NMR spectra was identified as the target compound II-9. The 1H NMR, 1C NMR, and fluorine NMR spectra are shown below:

[0149] 1 H NMR (400MHz, CDCl3) δ7.77–7.64(m,2H),7.05(t,J=8.1Hz,2H),5.97(s,1H),1.44(s,9H);

[0150] 13 C NMR (101MHz, CDCl3) δ165.8, 164.4 (d, J = 251.0Hz), 132.0 (d, J = 3.2Hz), 128.9 (d, J = 8.8Hz), 115.3 (d, J = 21.8Hz), 51.6, 28.8;

[0151] 19 F NMR (376MHz, CDCl3) δ-109.1.

[0152] Example 12 Synthesis of amide compound II-10

[0153]

[0154] 2-(tert-butylamino)-1-(3-chlorophenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 19 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 66%.

[0155] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-10. The 1H and 1C NMR spectra are shown below:

[0156] 1 H NMR (400MHz, CDCl3) δ7.68(s,1H),7.57(d,J=7.7Hz,1H),7.42(d,J=8.0Hz,1H),7.32(t,J=7.8Hz,1H),5.95(s,1H),1.46(s,9H);

[0157] 13 C NMR (101MHz, CDCl3) δ165.7,137.8,134.7,131.2,129.9,127.2,125.0,52.0,28.9.

[0158] Example 13 Synthesis of amide compound II-11

[0159]

[0160] 2-(tert-butylamino)-1-(4-chlorophenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 69%.

[0161] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-11. The 1H and 1C NMR spectra are shown below:

[0162] 1 H NMR (400MHz, CDCl3) δ7.64 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 5.96 (s, 1H), 1.45 (s, 9H);

[0163] 13 C NMR (101MHz, CDCl3) δ166.0,137.3,134.4,128.8,128.3,51.9,28.9.

[0164] Example 14 Synthesis of amide compound II-12

[0165]

[0166] 2-(tert-butylamino)-1-(3-bromophenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 63%.

[0167] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-12. The 1H and 1C NMR spectra are shown below:

[0168] 1H NMR (400MHz, CDCl3) δ7.77(s,1H),7.56(d,J=7.8Hz,1H),7.51(d,J=8.0Hz,1H),7.20(t,J=7.9Hz,1H),5.87(s,1H),1.39(s,9H);

[0169] 13 C NMR (101MHz, CDCl3) δ165.5,138.1,134.1,130.2,130.1,125.5,122.8,52.0,28.9.

[0170] Example 15 Synthesis of amide compound II-13

[0171]

[0172] 2-(tert-butylamino)-1-(4-bromophenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 16 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 66%.

[0173] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-13. The 1H and 1C NMR spectra are shown below:

[0174] 1 H NMR (400MHz, CDCl3) δ7.61–7.55(m,2H),7.55–7.49(m,2H),5.91(s,1H),1.46(s,9H);

[0175] 13 C NMR (101MHz, CDCl3) δ166.0,134.9,131.8,128.5,125.8,51.9,28.9.

[0176] Example 16 Synthesis of amide compound II-14

[0177]

[0178] 2-(tert-butylamino)-1-(3-(trifluoromethyl)phenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 19 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 60%.

[0179] The product obtained by detection using 1H NMR, 1C NMR, and fluorine NMR spectra was identified as the target compound II-14. The 1H NMR, 1C NMR, and fluorine NMR spectra are shown below:

[0180] 1 H NMR (400MHz, CDCl3) δ7.96(s,1H),7.87(d,J=7.8Hz,1H),7.69(d,J=7.8Hz,1H),7.51(t,J=7.8Hz,1H),6.07(s,1H),1.47(s,9H);

[0181] 13 C NMR (101MHz, CDCl3) δ165.6, 136.8, 131.1 (q, J = 32.7Hz), 130.1 (d, J = 1.4Hz), 12 9.2,127.7(q,J=3.7Hz),123.9(q,J=3.8Hz),123.9(q,J=272.5Hz),52.1,28.9;

[0182] 19 F NMR (376MHz, CDCl3) δ-62.7.

[0183] Example 17 Synthesis of amide compound II-15

[0184]

[0185] 2-(tert-butylamino)-1-(4-(trifluoromethyl)phenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 41%.

[0186] The product obtained by detection using 1H NMR, 1C NMR, and fluorine NMR spectra was identified as the target compound II-15. The 1H NMR, 1C NMR, and fluorine NMR spectra are shown below:

[0187] 1 H NMR (400MHz, CDCl3) δ7.80 (d, J = 8.1Hz, 2H), 7.64 (d, J = 8.1Hz, 2H), 6.03 (s, 1H), 1.47 (s, 9H);

[0188] 13 C NMR (101MHz, CDCl3) δ165.8, 139.4, 132.9 (q, J = 32.5Hz), 127.3, 125.6 (q, J = 3.7Hz), 123.8 (q, J = 272.5Hz), 52.1, 28.9;

[0189] 19 F NMR (376MHz, CDCl3) δ-62.9.

[0190] Example 18 Synthesis of amide compound II-16

[0191]

[0192] 2-(tert-butylamino)-1-(furan-2-yl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 58%.

[0193] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-16. The 1H and 1C NMR spectra are shown below:

[0194] 1 H NMR (600MHz, CDCl3) δ7.37 (d, J = 0.8Hz, 1H), 7.02 (d, J = 3.4Hz, 1H), 6.48–6.42 (m, 1H), 6.20 (s, 1H), 1.43 (s, 9H);

[0195] 13 C NMR (101MHz, CDCl3) δ157.9,148.9,143.4,113.5,112.2,51.5,29.0.

[0196] Example 19 Synthesis of amide compound II-17

[0197]

[0198] 2-(tert-butylamino)-1-(thiophen-2-yl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 42%.

[0199] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-17. The 1H and 1C NMR spectra are shown below:

[0200] 1 H NMR (400MHz, CDCl3) δ7.46–7.38(m,2H),7.07–6.99(m,1H),5.82(s,1H),1.45(s,9H);

[0201] 13 C NMR (101 MHz, CDCl3) δ 161.4, 140.7, 129.5, 127.6, 127.5, 52.1, 29.0. Example 20: Synthesis of amide compound II-18

[0202]

[0203] 2-(cyclohexylamino)-1-(thiophen-2-yl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 35%.

[0204] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-18. The 1H and 1C NMR spectra are shown below:

[0205] 1 H NMR(400MHz, CDCl3)δ7.47(d,J=3.7Hz,1H),7.44(d,J=5.0Hz,1H),7.14–6.99(m,1H),5.82(s,1H),4.05–3 .86(m,1H),2.10–1.97(m,2H),1.83–1.69(m,2H),1.69–1.60(m,1H),1.50–1.35(m,2H),1.28–1.18(m,3H)

[0206] 13 C NMR (101 MHz, CDCl3) δ 161.1, 139.6, 129.7, 127.8, 127.6, 48.9, 33.4, 25.7, 25.0. Example 21: Synthesis of amide compound II-19

[0207]

[0208] 2-(cyclopentanamino)-1-(4-methoxyphenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was placed under 385–400 nm light and stirred at 10 °C for 30 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product was obtained by separation and purification of the reaction system. It was a white solid with a yield of 57%.

[0209] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-19. The 1H and 1C NMR spectra are shown below:

[0210] 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.8Hz,2H),6.90(d,J=8.7Hz,2H),6.04(s,1H),4.38( q,J=6.9Hz,1H),3.83(s,3H),2.19–1.97(m,2H),1.86–1.56(m,4H),1.56–1.39(m,2H);

[0211] 13 C NMR (101MHz, CDCl3) δ166.9,162.2,128.8,127.1,113.8,55.5,51.8,33.4,23.9.

[0212] Example 22 Synthesis of amide compound II-20

[0213]

[0214] 2-(cyclohexylamino)-1-(4-methoxyphenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was placed under 385–400 nm light and stirred at 10 °C for 30 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product was obtained by separation and purification of the reaction system. It was a white solid with a yield of 49%.

[0215] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-20. The 1H and 1C NMR spectra are shown below:

[0216] 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.8Hz,2H),6.89(d,J=8.8Hz,2H),5.97(s,1H),4.05–3.88(m,1H),3.83 (s,3H),2.06–1.93(m,2H),1.80–1.69(m,2H),1.69–1.58(m,1H),1.50–1.34(m,2H),1.30–1.12(m,3H);

[0217] 13 C NMR (101 MHz, CDCl3) δ 166.2, 162.1, 128.7, 127.5, 113.8, 55.5, 48.7, 33.5, 25.7, 25.1. Example 23: Synthesis of amide compound II-21

[0218]

[0219] 2-(sec-butylamino)-1-(4-methoxyphenyl)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was placed under 385–400 nm light and stirred at 10 °C for 30 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product was obtained by separation and purification, and was a white solid with a yield of 41%.

[0220] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-21. The 1H and 1C NMR spectra are shown below:

[0221] 1 H NMR (400MHz, CDCl3) δ7.71 (d, J = 8.7Hz, 2H), 6.85 (d, J = 8.7Hz, 2H), 6.11 (s, 1H), 4.18–3. 99(m,1H),3.79(s,3H),1.61–1.44(m,2H),1.17(d,J=6.6Hz,3H),0.91(t,J=7.4Hz,3H);

[0222] 13C10 NMR (101 MHz, CDCl3) δ 166.5, 162.0, 128.7, 127.3, 113.6, 55.4, 47.0, 29.8, 20.6, 10.5. Example 24: Synthesis of amide compound II-22

[0223]

[0224] 0.5 mmol (1.0 eq.) of 1-(4-methoxyphenyl)-2-(pentan-3-ylamino)prop-1-one and 2.5 mL of acetonitrile were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. A dichloromethane solution (2.5 mL) of iodine (0.5 mmol (1.0 eq.) and triphenylphosphine (0.5 mmol (1.0 eq.)) was added to the above intermediate product system. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol (1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 44%.

[0225] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-22. The 1H and 1C NMR spectra are shown below:

[0226] 1 H NMR (400MHz, CDCl3) δ7.73(d,J=8.6Hz,2H),6.91(d,J=8.5Hz,2H),5.86(s,1H),4.07– 3.93(m,1H),3.84(s,3H),1.73–1.57(m,2H),1.55–1.40(m,2H),0.94(t,J=7.4Hz,6H);

[0227] 13 C NMR (151MHz, CDCl3) δ166.9,162.2,128.7,127.5,113.9,55.6,52.5,27.8,10.4.

[0228] Example 25 Synthesis of amide compound II-23

[0229]

[0230] 1-(4-methoxyphenyl)-2-((2,4,4-trimethylpentan-2-yl)amino)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. A dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added to the above intermediate product system. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product was obtained by separation and purification, and was a white solid with a yield of 43%.

[0231] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-23. The 1H and 1C NMR spectra are shown below:

[0232] 1 H NMR (400MHz, CDCl3) δ7.63 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 5.95 (s, 1H), 3.78 (s, 3H), 1.83 (s, 2H), 1.48 (s, 6H), 1.00 (s, 9H);

[0233] 13 C NMR (101 MHz, CDCl3) δ 166.3, 161.8, 128.5, 128.4, 113.7, 55.39, 55.36, 51.7, 31.7, 31.6, 29.4. Example 26: Synthesis of amide compound II-24

[0234]

[0235] 1-(4-methoxyphenyl)-2-((4-phenylbutan-2-yl)amino)prop-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was placed under 385–400 nm light and stirred at 10 °C for 30 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product was obtained by separation and purification, and was a white solid with a yield of 33%.

[0236] The product obtained by detection using 1H and 1C NMR spectra is the target compound II-24. The 1H and 1C NMR spectra are shown below:

[0237] 1 H NMR(400MHz, CDCl3) δ7.58(d,J=8.9Hz,2H),7.22–7.17(m,2H),7.16–7.07(m,3H),6.82(d,J=8.8Hz,2H),5.82( s,1H),4.28–4.09(m,1H),3.76(s,3H),2.64(t,J=7.9Hz,2H),1.81(q,J=8.6,8.2Hz,2H),1.20(d,J=6.6Hz,3H);

[0238] 13 C NMR (101 MHz, CDCl3) δ 166.5, 162.2, 141.9, 128.7, 128.6, 128.5, 127.2, 126.0, 113.8, 55.5, 45.8, 38.8, 32.7, 21.3. Example 27: Synthesis of amide compound II-25

[0239]

[0240] 0.5 mmol (1.0 eq.) of 4-(tert-butylcarbamoyl)phenyl 2-(4-isobutylphenyl)propionate and 2.5 mL of acetonitrile were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. A dichloromethane solution (2.5 mL) of iodine (0.5 mmol (1.0 eq.) and triphenylphosphine (0.5 mmol (1.0 eq.)) was added to the above intermediate product system. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol (1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 47%.

[0241] Detection is performed using nuclear magnetic resonance hydrogen and carbon spectra, such as Figure 3 and Figure 4 As shown, the obtained product is the target compound II-25, and its proton and carbon NMR spectra are as follows:

[0242] 1H NMR (400MHz, CDCl3) δ7.69(d,J=8.6Hz,2H),7.29(d,J=8.1Hz,2H),7.15(d,J=8.1Hz,2H),7.03(d,J=8.6Hz,2H),5.89(s,1H) ,3.94(q,J=7.2Hz,1H),2.47(d,J=7.2Hz,2H),1.92–1.82(m,1H),1.60(d,J=7.1Hz,3H),1.45(s,9H),0.91(d,J=6.6Hz,6H).

[0243] 13 C NMR (101MHz, CDCl3) δ173.0,166.2,153.1,141.1,137.1,133.6,129.7,128.2,127.3,121.6,51.8,45.4,45.2,30.3,29.0,22.5,18.6;

[0244] The melting point of the product, as determined by a melting point apparatus, is:

[0245] MP: 84.9-85.2℃;

[0246] The infrared spectral data of the detected product are as follows:

[0247] IR:2955,1705,1511,1460,1203,847cm -1 ;

[0248] The mass spectrometry results of the product are as follows:

[0249] HRMS(ESI)m / z:C 24 H 31 NO3[M+H] + Calculated value: 382.2377, measured value: 382.2393.

[0250] Example 28 Synthesis of amide compound II-26

[0251]

[0252] 0.5 mmol (1.0 eq.) of 4-(tert-butylcarbamoyl)phenyl 2-(7-methoxynaphth-2-yl)propionate and 2.5 mL of acetonitrile were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. A dichloromethane solution (2.5 mL) of iodine (0.5 mmol (1.0 eq.) and triphenylphosphine (0.5 mmol (1.0 eq.)) was added to the above intermediate product system. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol (1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 36%.

[0253] Detection is performed using nuclear magnetic resonance hydrogen and carbon spectra, such as Figure 5 and Figure 6 As shown, the obtained product is the target compound II-26, and its proton and carbon NMR spectra are as follows:

[0254] 1 H NMR (600MHz, CDCl3) δ7.77(s,1H),7.76(d,J=4.3Hz,1H),7.74(d,J=8.9Hz,1H),7.68(d,J=8.7Hz,2H),7.49(d,J=8.5Hz,1H),7.17(d ,J=8.9Hz,1H),7.14(s,1H),7.03(d,J=8.7Hz,2H),5.86(s,1H),4.13–4.08(m,1H),3.93(s,3H),1.69(d,J=7.2Hz,3H),1.45(s,9H);

[0255] 13 C NMR (151MHz, CDCl3) δ173.0,166.2,158.0,153.1,135.0,134.0,133.6,129.5,129 .1,128.2,127.6,126.3,126.2,121.6,119.3,105.8,55.5,51.8,45.7,29.0,18.6;

[0256] The melting point of the product, as determined by a melting point apparatus, is:

[0257] MP: 144.8-145.0℃;

[0258] The infrared spectral data of the detected product are as follows:

[0259] IR:3418,2970,1753,1662,1198,856cm -1 ;

[0260] The mass spectrometry results of the product are as follows:

[0261] HRMS(ESI)m / z:C 25 H 27 NO4[M+H] + Calculated value: 406.2013, measured value: 406.2013.

[0262] Example 29 Synthesis of amide compound II-27

[0263]

[0264] 4-(tert-butylcarbamoyl)phenyl 5-(2,5-dimethylphenoxy)-2,2-dimethylvalerate (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 50%.

[0265] Detection is performed using nuclear magnetic resonance hydrogen and carbon spectra, such as Figure 7 and Figure 8 As shown, the obtained product is the target compound II-27, and its proton and carbon NMR spectra are as follows:

[0266] 1 H NMR (400MHz, CDCl3) δ7.73(d,J=8.6Hz,2H),7.06(d,J=8.6Hz,2H),7.01(d,J=7.4Hz,1H),6.68(d,J=7.6Hz,1H),6.63 +

[0267] 13C NMR (101MHz, CDCl3) δ176.1,166.2,156.9,153.2,136.6,133.5,130.4,128.2,1 23.6,121.7,120.9,112.0,67.7,51.8,42.6,37.2,28.9,25.3,25.2,21.5,15.9.

[0268] The melting point of the product, as determined by a melting point apparatus, is:

[0269] MP: 82.2-82.7℃;

[0270] The infrared spectral data of the detected product are as follows:

[0271] IR:3453,2924,1750,1684,1507,1100cm -1 ;

[0272] The mass spectrometry results of the product are as follows:

[0273] HRMS(ESI)m / z:C 26 H 35 NO4[M+H] + Calculated value: 426.2639, measured value: 426.2639.

[0274] Example 30 Synthesis of amide compound II-28

[0275]

[0276] 4-(2-(tert-butylamino)pentanoyl)-N,N-dipropylbenzenesulfonamide (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 19 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The product was obtained by separation and purification. It was a white solid with a yield of 33%.

[0277] Detection is performed using nuclear magnetic resonance hydrogen and carbon spectra, such as Figure 9 and Figure 10 As shown, the obtained product is the target compound II-28, and its proton and carbon NMR spectra are as follows:

[0278] 1H NMR (400MHz, CDCl3) δ7.87–7.73(m,4H),6.08(s,1H),3.08–3.01(m,4H),1.55–1.49(m,4H),1.47(s,9H),0.85(t,J=7.4Hz,6H);

[0279] 13 C NMR (151 MHz, CDCl3) δ 165.7, 142.5, 139.6, 127.6, 127.3, 52.2, 50.0, 28.9, 22.0, 11.3. Example 31: Synthesis of amide compound II-1

[0280] 2-(tert-butylamino)-1-phenylpentan-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 19 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product, amide compound II-1, was obtained by separation and purification. It was a white solid with a yield of 55%.

[0281] Example 32 Synthesis of amide compound II-1

[0282] 2-(tert-butylamino)-1,4-diphenylbutane-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 12 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product, amide compound II-1, was obtained by separation and purification. It was a white solid with a yield of 69%.

[0283] Example 33 Synthesis of amide compound II-1

[0284] 2-(tert-butylamino)-1,5-diphenylpentan-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 19 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature, and the reaction endpoint was detected by TLC. The product, amide compound II-1, was obtained by separation and purification. It was a white solid with a yield of 52%.

[0285] Example 34 Synthesis of amide compound II-6

[0286] 2-(tert-butylamino)-1-(p-tolyl)hexane-1-one (0.5 mmol, 1.0 eq.) and acetonitrile (2.5 mL) were added to a reaction flask. The reaction system was stirred at room temperature under 385–400 nm light for 19 hours to obtain an intermediate product. To the above intermediate product system, a dichloromethane solution (2.5 mL) of iodine (0.5 mmol, 1.0 eq.) and triphenylphosphine (0.5 mmol, 1.0 eq.) was added. After stirring at room temperature for 5 minutes, triethylamine (0.8 mmol, 1.6 eq.) was added. The reaction system was stirred at room temperature. The reaction endpoint was detected by TLC. The reaction system was separated and purified to obtain the target compound II-6, a white solid, with a yield of 61%.

[0287] This invention provides a method for synthesizing amides using α-aminoarylacetone compounds, α-tert-butylamine arylacetone compounds, and their derivatives as raw materials. This method enables precise conversion of compounds with specific α-aminoketone structures, utilizes photochemical driving to reduce the energy consumption and stringent conditions required by traditional thermal reactions, provides a new pathway for the synthesis and modification of amide compounds, and expands the preparation methods for amide compounds in organic synthesis and related applications. The substrate applicability of this invention is somewhat expandable, enabling the derivatization of drug molecules such as ibuprofen, naproxen, gemfibrozil, and probenecid through reaction, expanding the diversity of drug molecule structures and providing technical support for the subsequent synthesis of drug intermediates and functional material precursors.

[0288] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0289] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing amide compounds through photochemical-driven synthesis, characterized in that, Using compound 1 of general formula as a raw material, after reacting in acetonitrile under light for time t, it is then reacted in a dichloromethane system of iodine, triphenylphosphine, and triethylamine to obtain product 1; The general reaction formula is as follows: Among them, R 1 It is selected from hydrogen, halogen, alkyl with 1 to 12 carbon atoms, alkoxy with 1 to 12 carbon atoms, cycloalkyl with 3 to 12 carbon atoms, halogen-substituted alkyl with 1 to 6 carbon atoms, halogen-substituted alkoxy with 1 to 6 carbon atoms, halogen-substituted cycloalkyl with 1 to 6 carbon atoms, aryl with 6 to 30 carbon atoms, and heteroaryl with 3 to 30 carbon atoms; R 2 Selected from alkyl groups having 3 to 12 carbon atoms and cycloalkyl groups having 3 to 12 carbon atoms; R 3 It is selected from alkyl groups having 1 to 12 carbon atoms and aryl groups having 6 to 30 carbon atoms; R 4 Selected from furanyl, thiopheneyl, aryl groups with 6 to 30 carbon atoms, and heteroaryl groups with 6 to 30 carbon atoms; If general formula compound 1 is in the form of hydrochloride salt, then the raw material needs to be added with a strong base in a molar ratio of 1:1 to general formula compound 1; the molar ratio of general formula compound 1, iodine, triphenylphosphine, and triethylamine is 1:1-10:1-10:1.6-16; The solvent is selected from at least one or a mixture of multiples of acetonitrile, chloroform, 1,2-dichloroethane, diethyl ether, and tetrahydrofuran.

2. The method for preparing the amide compound according to claim 1, characterized in that, The R 2 It is selected from secondary alkyl groups, tertiary alkyl groups, and cycloalkyl groups with 3 to 12 carbon atoms.

3. The method for preparing the amide compound according to claim 2, characterized in that, The R 2 For tert-butyl; The R 3 It is selected from alkyl groups having 1 to 12 carbon atoms and aryl groups having 6 to 30 carbon atoms; If compound 1 is in the form of hydrochloride, then sodium hydroxide in a molar ratio of 1:1 with compound 1 is added to the raw material.

4. The method for preparing the amide compound according to claim 1, characterized in that, The R 3 It is methyl; The R 2 It is selected from secondary alkyl groups, tertiary alkyl groups, cyclopentyl groups, and cyclohexyl groups with 3 to 12 carbon atoms.

5. The method for preparing the amide compound according to claim 1, characterized in that, The R 4 Selected from furanyl, thiopheneyl, and arylene groups with 6 to 30 carbon atoms; R 1 It is selected from hydrogen, halogen, alkyl with 1 to 12 carbon atoms, alkoxy with 1 to 12 carbon atoms, cycloalkyl with 3 to 12 carbon atoms, halogen-substituted alkyl with 1 to 6 carbon atoms, halogen-substituted alkoxy with 1 to 6 carbon atoms, halogen-substituted cycloalkyl with 1 to 6 carbon atoms, aryl with 6 to 30 carbon atoms, and heteroaryl with 3 to 30 carbon atoms.

6. The method for preparing the amide compound according to claim 5, characterized in that, R 4 Selected from furanyl, thiopheneyl, and phenylene; R 1 It is selected from hydrogen, halogen, alkyl with 1 to 12 carbon atoms, alkoxy with 1 to 12 carbon atoms, cycloalkyl with 3 to 12 carbon atoms, halogen-substituted alkyl with 1 to 6 carbon atoms, halogen-substituted alkoxy with 1 to 6 carbon atoms, halogen-substituted cycloalkyl with 1 to 6 carbon atoms, aryl with 6 to 30 carbon atoms, and heteroaryl with 3 to 30 carbon atoms.

7. The method for preparing the amide compound according to any one of claims 1-5, characterized in that, The wavelength range of the illumination is 385–400 nm.

8. The method for preparing the amide compound according to any one of claims 1-5, characterized in that, The reaction time t is selected from 12 to 30 hours.

9. The method for preparing the amide compound according to any one of claims 1-5, characterized in that, The solvent is selected from at least one of acetonitrile, chloroform, 1,2-dichloroethane, diethyl ether, and tetrahydrofuran.

10. The method for preparing the amide compound according to any one of claims 1-5, characterized in that, The molar ratio of the general formula compound 1, iodine, triphenylphosphine, and triethylamine is 1:1:1:1.6.

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