A method for synthesizing α,β-unsaturated acetylene amides directly induced by visible light.

Abstract

This invention discloses a visible light-induced method for synthesizing α,β-unsaturated acetylide amides, belonging to the field of organic synthesis. The invention constructs a visible light-responsive aromatization-driven carbamoyl radical precursor—a dihydroquinazolinone derivative precursor containing a carbamoyl segment. Under direct visible light irradiation, a single-electron process is triggered, leading to C-C bond cleavage and aromatization, thereby efficiently releasing a carbamoyl radical in situ. Subsequently, this radical undergoes selective acetylation transfer and coupling with an acetylation-based high-valent iodine reagent, achieving the rapid construction of the target α,β-unsaturated acetylide amide. This process can be completed via a one-pot pathway of "visible light direct-driven—radical generation—acetylation transfer / coupling," avoiding the introduction of additional photocatalysts, making the reaction system simpler, the cost more controllable, and the post-processing more convenient.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing α,β-unsaturated acetylene amides directly induced by visible light. Background Technology

[0002] α,β-Unsaturated acetylides are a class of highly activated molecular structural units possessing characteristics of both acetylide bonds and amide functional groups. Due to the polarization and electronic regulation of the carbon-carbon triple bond by the amide group, these compounds exhibit unique advantages in reaction selectivity, regiocontrol, and subsequent transformations, and have been widely used in heterocycle construction, tandem reactions, cycloaddition reactions, and selective functional group transformations. Furthermore, the α,β-unsaturated acetylide skeleton is frequently found in bioactive molecules, natural product derivatives, and functional materials; therefore, developing efficient, mild synthetic methods with good functional group compatibility is of great significance.

[0003] Currently, the construction of α,β-unsaturated acetylides mainly relies on the following strategies: First, constructing C(sp)-N or C(sp)-C bonds through the coupling reaction of alkynes with amide precursors catalyzed by transition metals (such as Pd, Cu, Ni, etc.); second, forming the acetylide skeleton through carbon monoxide-mediated amino carbonylation reactions or conversion of acetylic acid derivatives; and third, using alkyne activation under strong base or strong oxidant conditions to couple with amine substrates to generate the target product. While these methods have achieved efficient preparation of acetylides to some extent, they generally suffer from the following drawbacks: the reaction conditions are relatively harsh and sensitive to water and oxygen; expensive or highly toxic transition metal catalysts are required; some systems rely on high temperature, high pressure, or carbon monoxide gas, posing safety hazards; furthermore, the problems of strong oxidants or metal residues limit their application in the late-stage modification of complex molecules and in pharmaceutical chemistry.

[0004] In recent years, visible light-driven radical reactions have attracted widespread attention as an important development direction in green synthetic chemistry. Visible light has advantages such as abundant sources, low energy consumption, and environmental friendliness. Through photoinduced single-electron transfer (SET) processes, it can achieve the construction and breaking of various bonds under mild conditions. In the field of acetylide amide construction, researchers have gradually explored strategies to achieve the direct formation of C(sp)-C bonds by coupling carbamoyl radicals with acetylide transfer reagents. In particular, high-valent iodine(III) acetylide reagents (such as EBX or BI-type reagents) have become important tools for constructing acetylide amide structures due to their good functional group compatibility and excellent acetylide transfer ability. However, most existing radical-based acetylide amide synthesis methods still rely on the addition of external photocatalysts (such as Ru, Ir complexes, or organic dyes) and chemical oxidants to initiate the reaction. This not only increases the complexity and cost of the system, but may also trigger side reactions or reduce reaction selectivity. At the same time, the addition of photocatalysts may lead to metal residues or purification difficulties in some complex substrate systems, which is not conducive to scale-up production and drug molecule modification. Therefore, developing a new method for constructing α,β-unsaturated acetylene amides under mild conditions without the need for external photocatalysts has significant application potential.

[0005]

[0006] A method for synthesizing α,β-unsaturated acetylene amides has been reported.

[0007] Therefore, designing a structurally stable, easily prepared precursor molecule capable of directly generating carbamoyl radicals under visible light irradiation, and efficiently coupling it with a high-valent iodoalkynyl reagent to construct α,β-unsaturated alkynylamides without the need for an external photocatalyst, is a pressing technical problem in this field. Achieving this goal would help simplify the reaction system, reduce costs, improve the greenness and practicality of the reaction, and provide a more convenient technical means for the later-stage alkynylation modification of complex molecules. Based on this background, developing a visible light-induced, catalyst-free, mild, and substrate-compatible method for the synthesis of α,β-unsaturated alkynylamides is of great significance for promoting the development of alkynylamide chemistry and visible light organic synthesis. Summary of the Invention

[0008] Given that the synthesis of existing acetylides and their conjugated derivatives often relies on transition metal catalysis, strong bases, or stoichiometric redox systems, which involve relatively harsh conditions, cumbersome steps, and insufficient compatibility with functional groups and scale-up preparation, this invention provides a visible light-induced method for the synthesis of α,β-unsaturated acetylides. This method directly induces the reaction to prepare α,β-unsaturated acetylides under visible light irradiation without the need for an external photosensitizer. This method uses visible light as the sole driving force, exhibits mild reaction conditions, and is highly modular, enabling the rapid construction of structurally diverse α,β-unsaturated acetylide skeletons.

[0009] Based on previous research and mechanistic assumptions, this invention constructs a visible-light-responsive aromatization-driven carbamoyl radical precursor—a dihydroquinazolinone derivative precursor containing a carbamoyl group. Under direct visible light irradiation, this precursor undergoes a single-electron process, triggering C / C bond cleavage and aromatization, thereby efficiently releasing a carbamoyl radical in situ. Subsequently, this radical undergoes selective alkynyl transfer and coupling with a high-valent alkynyl iodine reagent (such as EBX / BI-type alkynyl donors), achieving the rapid construction of the target α,β-unsaturated alkynylamide. This process can be completed via a one-pot pathway of "direct visible light driving—radical generation—alkynyl transfer / coupling," avoiding the introduction of additional photocatalysts, making the reaction system simpler, the cost more controllable, and the post-processing more convenient.

[0010] The present invention provides a method for synthesizing α,β-unsaturated acetylene amides directly induced by visible light, comprising the following steps:

[0011] The dihydroquinazolinone derivative precursor 1 (1 equivalent), containing a carbamoyl fragment, 2 (1.5 equivalents), sodium dihydrogen phosphate (2 equivalents), and a stir bar were added to a photoreaction tube. The N2 was replaced three times through a double-row tube. Anhydrous solvent was added, and the reaction was stirred under blue light or other visible light sources. After the reaction was completed, the target product α,β-unsaturated acetylene amide 3 was obtained by conventional post-processing and separation and purification.

[0012] The solvent is dichloromethane.

[0013] The reaction temperature was room temperature.

[0014] The synthesis route is shown below:

[0015] .

[0016] R in compounds 1 and 2 1 R 2 and R 3Each of the following is independently selected from hydrogen, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C3-C10 cycloalkyl, and substituted or unsubstituted aryl. R 1 R 2 It can also form rings. Substituents used for substitution include one or more of O, N, Si, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, and phenyl.

[0017] The separation and purification are carried out by recrystallization or silica gel column chromatography, with the eluent being petroleum ether and ethyl acetate (volume ratio 5:1-1:1) or dichloromethane and methanol (volume ratio 20:1-10:1).

[0018] This method offers advantages such as mild conditions, simple operation, no need for external photosensitizers / photocatalysts, wide substrate applicability, and good functional group compatibility. In particular, this strategy can cover the generation of different levels (primary / secondary / tertiary) carbamoyl radicals and achieve modular combination with diverse alkyne-based high-valent iodine donors, enabling the convenient preparation of structurally diverse α,β-unsaturated alkyne amides. This provides a new visible light-induced direct synthetic route for the efficient construction of conjugated alkyne amide skeletons and lays the foundation for its further applications in addition, coupling, deprotection, and material / drug fragment derivatization.

[0019] The reaction process may be as follows (see diagram): Under blue LED irradiation, 1a is excited to a photoexcited state. This state allows 1a* to perform a single-electron reduction of 2a, generating an I radical cation, along with the production of a BI radical and phenylacetylene. The I radical cation then cleaves into an amino radical (II), releasing byproduct III. The carbamoyl radical (II) is captured by 2a to form a radical intermediate IV. This intermediate can be further converted to product 3aa and regenerate the BI radical. Ultimately, the BI radical participates in the radical chain propagation, promoting the conversion of 1a* into the radical cation I.

[0020] In the target products of this invention, some compounds themselves have biological activity, or can be used as intermediates to prepare the next target product.

[0021] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0022] 1. The raw materials are stable, widely available, and easy to prepare; they can be obtained through simple conversion or purchased commercially.

[0023] 2. The reaction can be directly driven by visible light, without the need for additional photocatalysts / photosensitizers, thus avoiding the introduction of other components, especially transition metals.

[0024] 3. The reaction conditions are mild and can be carried out at room temperature; the system is simple, requiring only the addition of inorganic salts in addition to the reactants.

[0025] 4. It has broad substrate compatibility and can successfully react with primary, secondary, and tertiary amide radical precursors.

[0026] 5. It is compatible with amino acids, oligopeptides, and bioactive molecules, enabling N-terminal acetylation reactions. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the reaction mechanism of the present invention. Detailed Implementation

[0028] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0029] Example 1:

[0030]

[0031] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 3 as a yellow solid, in 83% yield.

[0032] Other optimization conditions are as follows: a :

[0033]

[0034]

[0035] a Reaction conditions: 1a (0.2 mmol, 1.0 equiv.); 2a (0.24 mmol, 1.2 equiv.); solvent (2 mL); NaH2PO4 (0.4 mmol); blue light 450-465 nm. b Separation yield. c No NaH2PO4. d 2a (0.2 mmol, 1 equiv.). e 2a (0.3 mmol, 1.5 equiv.). f 2a (0.4 mmol, 2 equiv.). gNo photocatalyst, 2a (0.3 mmol, 1.5 equiv.). i No photocatalyst or light.

[0036] First, different photosensitizers were screened. Using acridine-type photosensitizers PC1, PC3, ruthenium tripyridine PC3, and triphenylpyranium PC4, it was found that PC1 yielded product 3aa in 73% yield. Experiments with different solvents, such as 1,2-dichloroethane, ethyl acetate, acetonitrile, and tetrahydrofuran, resulted in decreased yields (27-68%). Reducing the amount of trivalent iodoacetylene reagent 2a to 1.0 equivalent decreased the yield to 70%; increasing 2a to 1.5 equivalent increased the yield to 78%; further increasing 2a to 2.0 equivalent decreased the yield again. When no photosensitizer was added, product 3aa yielded 83%. Control experiments showed that the reaction could not proceed without photosensitizer and under light-free conditions. The optimal reaction conditions were determined to be 1.0 equivalent of substrate 1a, 1.5 equivalent of substrate 2a, and two equivalents of NaH2PO4 under blue light.

[0037] Compound 3 was tested and found to be:

[0038] 1 H NMR (500 MHz, Chloroform-d) δ 7.46-7.42 (m, 2H), 7.40-7.37 (m,1H), 7.37-7.34 (m, 2H), 7.33-7.28 (m, 1H), 7.25-7.20 (m, 2H), 7.15 -7.11 (m,2H), 3.38 (s, 3H).

[0039] 13 C NMR (125 MHz, Chloroform-d) δ 154.2, 143.2, 132.3, 129.8, 129.1, 128.2, 127.9, 127.3, 120.4, 90.8, 82.5, 36.3.

[0040] High resolution: Calculated value: [M+H + ] + 236.1075, measured value: 236.1078.

[0041] Example 2:

[0042]

[0043] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1b (62.6 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and then anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 4 as a white solid in 88% yield.

[0044] Compound 4 was tested and found to be:

[0045] 1 H NMR (500 MHz, Chloroform-d) δ 7.36-7.31 (m, 3H), 7.28-7.23 (m,2H), 7.19-7.11 (m, 4H), 3.36 (s, 3H).

[0046] 13 C NMR (125 MHz, Chloroform-d) δ 161.8 (d, J = 246.4 Hz), 154.2,139.2 (d, J = 3.3 Hz), 132.3, 130.0, 129.2 (d, J = 8.6 Hz), 128.3, 120.2,116.0 (d, J = 22.5 Hz), 91.1, 82.3, 36.4.

[0047] 19 F NMR (471 MHz, Chloroform-d) δ -113.2.

[0048] High resolution: Calculated value: [M+H + ] + 254.0981, measured value: 254.0984.

[0049] Example 3:

[0050]

[0051] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1c (61.9 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and then anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 5 as a yellow solid, in 90% yield.

[0052] Compound 5 was tested:

[0053] 1 H NMR (500 MHz, Chloroform-d) δ 7.47-7.40 (m, 3H), 7.34-7.28 (m,3H), 7.23-7.19 (m, 2H), 7.13-7.05 (m, 2H), 3.87 (q, J = 7.5 Hz, 2H), 1.18 (t,J = 7.5 Hz, 3H).

[0054] 13 C NMR (125 MHz, Chloroform-d) δ 153.9, 141.7, 132.4, 129.8, 129.1, 128.6, 128.2, 128.1, 120.5, 90.7, 82.8, 43.4, 12.9.

[0055] High resolution: Calculated value: [M+H + ] + 250.1232, measured value: 250.1235.

[0056] Example 4:

[0057]

[0058] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1d (60.3 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 6 as a yellow solid, in 50% yield.

[0059] Compound 6 was tested and found to be:

[0060] 1H NMR (500 MHz, Chloroform-d) δ 7.56-7.49 (m, 2H), 7.43-7.31 (m,3H), 4.47-4.22 (m, 1H), 3.14 (s, 1H), 2.89 (s, 2H), 1.91-1.66 (m, 5H), 1.57-1.48 (m, 1H), 1.47-1.31 (m, 3H), 1.17-1.07 (m, 1H).

[0061] 13 C NMR (125 MHz, Chloroform-d) δ 154.3, 154.3, 132.3, 132.2, 129.8,129.8, 128.5, 128.4, 120.8, 120.8, 90.0, 89.8, 82.3, 81.7, 58.6, 52.3, 31.1,30.9, 29.6, 26.9, 25.8, 25.5, 25.5, 25.2.

[0062] High resolution: Calculated value: [M+H + ] + 242.1545, measured value: 242.1548.

[0063] Example 5:

[0064]

[0065] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1e (51.9 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and then anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 7 as a yellow solid, in 98% yield.

[0066] Compound 7 was tested and found to be:

[0067] 1H NMR (500 MHz, Chloroform-d) δ 7.55-7.49 (m, 2H), 7.44-7.37 (m,1H), 7.37-7.30 (m, 2H), 3.72 (t, J = 6.5 Hz, 2H), 3.52 (t, J = 6.5 Hz, 2H),2.01 – 1.86 (m, 4H).

[0068] 13 C NMR (125 MHz, Chloroform-d) δ 152.7, 132.3, 129.9, 128.4, 120.6, 88.6, 82.6, 48.1, 45.3, 25.3, 24.7.

[0069] High resolution: Calculated value: [M+H + ] + 200.1075, measured value: 200.1078.

[0070] Example 6:

[0071]

[0072] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1f (55.1 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 8, a yellow oily substance, in 86% yield.

[0073] Compound 8 was tested and found to be:

[0074] 1 H NMR (500 MHz, Chloroform-d) δ 7.55-7.51 (m, 2H), 7.44-7.39 (m,1H), 7.38-7.33 (m, 2H), 3.85-3.81 (m, 2H), 3.75-3.72 (m, 2H), 3.69 (s, 4H).

[0075] 13C NMR (125 MHz, Chloroform-d) δ 153.1, 132.3, 130.1, 128.5, 120.2, 91.1, 80.7, 66.8, 66.4, 47.3, 41.9.

[0076] High resolution: Calculated value: [M+H + ] + 216.1025, measured value: 216.1028.

[0077] Example 7:

[0078]

[0079] In a dry 10 mL reaction tube, 1 g (64.3 mg, 0.2 mmol) of amide-substituted dihydroquinazolinone, 104.4 mg (0.3 mmol) of high-valent iodothyne 2a, 48.0 mg (4.0 mmol) of sodium dihydrogen phosphate, and a magnetic spool were added. The mixture was purged three times with nitrogen in a double-row tube, and then 2 mL of anhydrous dichloromethane (DCM) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 9 as a yellow oil in 75% yield.

[0080] Compound 9 was tested and found to be:

[0081] 1 H NMR (500 MHz, Chloroform-d) δ 7.61-7.55 (m, 2H), 7.46-7.35 (m,3H), 7.24-7.14 (m, 4H), 4.98 (s, 1H), 4.82 (s, 1H), 4.08 (t, J = 6.0 Hz, 1H), 3.91 (t, J = 6.0 Hz, 1H), 2.98 (t, J = 6.0 Hz, 1H), 2.92 (t, J = 6.0 Hz, 1H).

[0082] 13 C NMR (125 MHz, Chloroform-d) δ 153.7, 134.6, 133.8, 132.4, 132.3,132.3, 130.0, 128.9, 128.6, 128.5, 127.0, 126.7, 126.7, 126.6, 126.5, 126.1,120.5, 90.3, 81.3, 48.6, 44.7, 44.0, 39.6, 29.5, 28.3.

[0083] High resolution: Calculated value: [M+H + ] + 262.1232, measured value: 262.1234.

[0084] Example 8:

[0085]

[0086] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1h (56.3 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 10 as a yellow solid, in 70% yield.

[0087] Compound 10 was tested and found to be:

[0088] 1 H NMR (500 MHz, Chloroform-d) δ 7.77 (s, 1H), 7.57 (t, J = 8.5 Hz, 4H), 7.43 (t, J = 7.5 Hz, 1H), 7.39-7.32 (m, 4H), 7.15 (t, J = 7.5 Hz, 1H).

[0089] 13 C NMR (125 MHz, Chloroform-d) δ 151.0, 137.3, 132.6, 130.3, 129.1, 128.6, 124.9, 119.9, 119.9, 85.7, 83.4.

[0090] High resolution: Calculated value: [M+H + ] + 222,0919, measured value: 222.0918.

[0091] Example 9:

[0092]

[0093] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1i (59.0 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 11 as a yellow solid, in 74% yield.

[0094] Compound 11 was tested and found to be:

[0095] 1 H NMR (500 MHz, Chloroform-d) δ 7.82 (s, 1H), 7.55-7.52 (m, 2H), 7.51-7.48 (m, 2H), 7.44 -7.40 (m, 1H), 7.37-7.33 (m, 2H), 6.88 – 6.84 (m,2H), 3.79 (s, 3H).

[0096] 13 C NMR (100 MHz, DMSO-d6) δ 156.3, 150.4, 132.7, 132.1, 130.9, 129.5, 121.6, 120.2, 114.5, 84.8, 84.5, 55.7.

[0097] High resolution: Calculated value: [M+H + ] + 252.1025, measured value: 252.1019.

[0098] Example 10:

[0099]

[0100] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1j (63.2 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 12 as a yellow oil, in 67% yield.

[0101] Compound 12 was tested and found to be:

[0102] 1H NMR (500 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.70-7.63 (m, 4H), 7.57-7.52 (m, 1H), 7.52 -7.47 (m, 2H), 7.43-7.39 (m, 2H).

[0103] 13 C NMR (100 MHz, DMSO-d6) δ 150.3, 137.4, 132.3, 130.6, 129.1, 128.8, 127.8, 121.2, 119.4, 84.7, 84.0.

[0104] High resolution: Calculated value: [M+H + ] + 256.0529, measured value: 256.0532.

[0105] Example 11:

[0106]

[0107] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (57.5 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 13 as a yellow oil in 86% yield.

[0108] Compound 13 was tested and found to be:

[0109] 1 H NMR (500 MHz, Chloroform-d) δ 7.55-7.50 (m, 2H), 7.41-7.36 (m,1H), 7.36-7.31 (m, 2H), 5.97-5.83 (m, 1H), 3.91-3.83 (m, 1H), 2.02-1.94 (m,2H), 1.76 – 1.69 (m, 2H), 1.65-1.59 (m, 1H), 1.42-1.32 (m, 2H), 1.25-1.16 (m,3H).

[0110] 13C NMR (125 MHz, Chloroform-d) δ 152.5, 132.4, 129.9, 128.4, 120.3, 84.1, 83.3, 48.8, 32.8, 25.4, 24.7.

[0111] High resolution: Calculated value: [M+H + ] + 228.1388, measured value: 228.1391.

[0112] Example 12:

[0113]

[0114] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1L (52.3 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 14 as a yellow solid, in 76% yield.

[0115] Compound 14 was tested and found to be:

[0116] 1 H NMR (500 MHz, Chloroform-d) δ 7.52-7.48 (m, 2H), 7.41-7.36 (m,1H), 7.35-7.30 (m, 2H), 5.83 (s, 1H), 1.40 (s, 9H).

[0117] 13 C NMR (125 MHz, Chloroform-d) δ 152.5, 132.3, 129.7, 128.4, 120.4, 84.1, 82.5, 52.4, 28.6.

[0118] High resolution: Calculated value: [M+ Na] + ] + 224.1051, measured value: 224.1054.

[0119] Example 13:

[0120]

[0121] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1m (41.1 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 15 as a yellow oil, in 92% yield.

[0122] Compound 15 was tested and found to be:

[0123] 1 H NMR (500 MHz, Chloroform-d) δ 7.55-7.52 (m, 2H), 7.44-7.40 (m,1H), 7.37-7.33 (m, 2H), 6.63 (s, 1H), 6.07 (s, 1H).

[0124] 13 C NMR (125 MHz, Chloroform-d) δ 155.6, 132.6, 130.3, 128.5, 119.8, 86.2, 82.2.

[0125] High resolution: Calculated value: [M+H + ] + 146.0606, measured value: 146.0609.

[0126] Example 14:

[0127]

[0128] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1n (58.3 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 16 as a yellow solid in 85% yield.

[0129] Compound 16 was tested and found to be:

[0130] 1H NMR (500 MHz, Chloroform-d) δ 7.55-7.52 (m, 2H), 7.43-7.39 (m,1H), 7.37-7.33 (m, 2H), 6.59 (d, J = 7.5 Hz, 1H), 4.69 (p, J = 7.0 Hz, 1H), 3.78 (s, 3H), 1.47 (d, J = 7.0 Hz, 3H).

[0131] 13 C NMR (125 MHz, Chloroform-d) δ 172.8, 152.7, 132.5, 130.2, 128.5, 120.0, 85.3, 82.6, 52.6, 48.4, 18.3.

[0132] High resolution: Calculated value: [M+ Na] + ] + 254.0793, measured value: 254.0797.

[0133] Example 15:

[0134]

[0135] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1o (63.9 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 17 as a yellow solid, in 75% yield.

[0136] Compound 17 was tested and found to be:

[0137] 1 H NMR (500 MHz, Chloroform-d) δ 7.55-7.52 (m, 2H), 7.42-7.38 (m,1H), 7.36-7.32 (m, 2H), 6.52 (d, J = 9.0 Hz, 1H), 4.65 (dd, J = 9.0, 5.0 Hz,1H), 3.75 (s, 3H), 2.25-2.17 (m, 1H), 0.98 (d, J =7.0 Hz, 3H), 0.95 (d, J =7.0 Hz, 3H).

[0138] 13 C NMR (125 MHz, Chloroform-d) δ 171.8, 153.1, 132.5, 130.1, 128.5, 120.0, 85.5, 82.6, 57.3, 52.3, 31.4, 18.8, 17.8.

[0139] High resolution: Calculated value: [M+ Na] + ] + 282.1106, measured value: 282.1110.

[0140] Example 16:

[0141]

[0142] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1p (66.7 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 18 as a yellow solid, in 71% yield.

[0143] Compound 18 was tested and found to be:

[0144] 1 H NMR (500 MHz, Chloroform-d) δ 7.54-7.51 (m, 2H), 7.43-7.38 (m,1H), 7.37-7.32 (m, 2H), 6.43 (d, J = 9.0 Hz, 1H), 4.76-4.71 (m, 1H), 3.75 (s,3H), 1.74-1.67 (m, 2H), 1.64-1.56 (m, 1H), 0.96 (t, J = 6.5 Hz, 6H).

[0145] 13 C NMR (125 MHz, Chloroform-d) δ 172.9, 152.9, 132.5, 130.1, 128.5, 120.0, 85.5, 82.6, 52.4, 51.0, 41.6, 24.8, 22.7, 21.9.

[0146] High resolution: Calculated value: [M+ Na] + ]+ 296.1263, measured value: 296.1266.

[0147] Example 17:

[0148]

[0149] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1q (73.5 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 19 as a yellow solid, with a yield of 94%.

[0150] Compound 19 was tested and found to be:

[0151] 1 H NMR (500 MHz, Chloroform-d) δ 7.55-7.52 (m, 2H), 7.44-7.40 (m,1H), 7.38-7.30 (m, 4H), 7.28-7.25 (m, 1H), 7.16-7.13 (m, 2H), 6.43 (d, J =8.0 Hz, 1H), 5.01-4.96 (m, 1H), 3.75 (s, 3H), 3.25-3.14 (m, 2H).

[0152] 13 C NMR (125 MHz, Chloroform-d) δ 171.3, 152.7, 135.4, 132.6, 130.2,129.3, 128.6, 128.5, 127.2, 120.0, 85.5, 82.5, 53.5, 52.5, 37.7.

[0153] High resolution: Calculated value: [M+ H + ] + 330.1106, measured value: 330.1109.

[0154] Example 18:

[0155]

[0156] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1r (93.3 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and then anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 20 as a green solid, in 71% yield.

[0157] Compound 20 was tested and found to be:

[0158] 1 H NMR (500 MHz, Chloroform-d) δ 7.52-7.48 (m, 2H), 7.41-7.37 (m,1H), 7.35-7.29 (m, 2H), 7.29-7.20 (m, 5H), 7.03-6.94 (m, 1H), 6.64-6.54 (m,1H), 4.94-4.88 (m, 1H), 4.44 (dd, J = 8.5, 5.0 Hz, 1H), 3.69 (s, 3H), 3.13(d, J = 7.0 Hz, 2H), 2.14-2.06 (m, 1H), 0.87 (d, J = 7.0 Hz, 3H), 0.85 (d, J= 7.0 Hz, 3H).

[0159] 13 C NMR (125 MHz, Chloroform-d) δ 171.5, 170.3, 153.0, 136.0, 132.5,130.1, 129.3, 128.6, 128.4, 127.0, 119.9, 85.7, 82.5, 57.5, 54.8, 52.0, 38.3, 31.0, 18.8, 17.7.

[0160] High resolution: Calculated value: [M+ Na] + ] + 429.1790, measured value: 429.1793.

[0161] Example 19:

[0162]

[0163] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1s (86.9 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 21 as a yellow solid, in 66% yield.

[0164] Compound 21 was tested and found to be:

[0165] 1 H NMR (500 MHz, Chloroform-d) δ 7.54-7.47 (m, 2H), 7.41-7.35 (m,1H), 7.34-7.29 (m, 2H), 7.27-7.18 (m, 1H), 7.08-6.96 (m, 1H), 4.70-4.64 (m,1H), 4.61-4.5 (m, 1H), 3.73 (d, J = 3.0 Hz, 3H), 3.62 (d, J = 3.3 Hz, 3H), 2.47-2.34 (m, 2H), 2.25-2.17 (m, 1H), 2.07-1.96 (m, 1H), 1.44 (d, J = 7.0 Hz, 3H).

[0166] 13 C NMR (125 MHz, Chloroform-d) δ 173.2, 171.8, 152.9, 132.5, 130.1,128.4, 119.9, 85.6, 82.5, 52.5, 51.8, 51.8, 49.1, 29.91, 26.8, 18.5.

[0167] High resolution: Calculated value: [M+ Na] + ] + 397.1376, measured value: 397.1377.

[0168] Example 20:

[0169]

[0170] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1t (72.9 mg, 0.2 mmol), high-valent iodothyne 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 22 as a white solid in 80% yield.

[0171] Compound 22 was tested and found to be:

[0172] H NMR (500 MHz, Chloroform-d) δ 7.56-7.53 (m, 2H), 7.44-7.40 (m, 1H), 7.38-7.34 (m, 2H), 7.03-6.99 (m, 2H), 6.96-6.92 (m, 1H), 6.46 (d, J = 8.5 Hz,1H), 4.48 – 4.42 (m, 1H), 3.87 (dd, J = 9.0, 4.0 Hz, 1H), 3.76 (dd, J = 9.0,3.5 Hz, 1H), 2.30 (s, 6H), 1.48 (d, J = 7.0 Hz, 3H).

[0173] 13 C NMR (100 MHz, DMSO-d6) δ 155.5, 152.4, 132.6, 130.8, 130.7, 129.4, 129.3, 124.2, 120.4, 84.6, 83.5, 74.0, 45.9, 17.3, 16.4.

[0174] High resolution: Calculated value: [M+H + ] + 308.1651, measured value: 308.1653.

[0175] Example 21:

[0176]

[0177] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1u (94.7 mg, 0.2 mmol), high-valent iodoacetylene 2a (104.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 23 as a white solid, in 94% yield.

[0178] Compound 23 was tested and found to be:

[0179] 1 H NMR (500 MHz, Chloroform-d) δ 7.59-7.52 (m, 2H), 7.42-7.38 (m,1H), 7.36-7.32 (m, 2H), 7.20 (d, J = 8.0 Hz, 1H), 7.04-7.00 (m, 1H), 6.94-6.92 (m, 1H), 6.08-6.01 (m, 1H), 3.47-3.32 (m, 1H), 3.23-3.17 (m, 1H), 2.98-2.81 (m, 3H), 2.34-2.29 (m, 1H), 1.96-1.90 (m, 1H), 1.82-1.68 (m, 3H), 1.52-1.47 (m, 2H), 1.44-1.34 (m, 2H), 1.26-1.22 (m, 9H), 0.99 (s, 3H).

[0180] 13 C NMR (100 MHz, Chloroform-d) δ 153.6, 147.0, 145.6, 134.7, 132.4,129.9, 128.4, 126.9, 124.1, 123.8, 120.2, 84.8, 83.2, 50.0, 45.0, 38.2, 37.6,37.4, 36.1, 33.4, 30.1, 29.6, 25.2, 23.9, 18.9, 18.7, 18.5.

[0181] High resolution: Calculated value: [M+H + ] + 414.2797, measured value: 414.2799.

[0182] Example 22:

[0183]

[0184] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodothyne 2b (108.7 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and then anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 24 as a yellow solid, in 63% yield.

[0185] Compound 24 was tested and found to be:

[0186] 1 H NMR (500 MHz, Chloroform-d) δ 7.46-7.41 (m, 2H), 7.39-7.34 (m,3H), 7.05-7.01 (m, 4H), 3.38 (s, 3H), 2.29 (s, 3H).

[0187] 13 C NMR (125 MHz, Chloroform-d) δ 154.4, 143.3, 140.4, 132.3, 129.1, 129.0, 127.8, 127.4, 117.3, 91.2, 82.2, 36.3, 21.5.

[0188] High resolution: Calculated value: [M+H + ] + 250.1232, measured value: 250.1235.

[0189] Example 23:

[0190]

[0191] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodoacetylene 2c (109.8 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic stir bar were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 25 as a yellow solid, in 95% yield.

[0192] Compound 25 was tested and found to be:

[0193] 1H NMR (500 MHz, Chloroform-d) δ 7.46-7.41 (m, 2H), 7.40-7.37 (m,1H), 7.36-7.32 (m, 2H), 7.12-7.08 (m, 2H), 6.91 (t, J=8.5 Hz, 2H), 3.37 (s,3H).

[0194] 13 C NMR (125 MHz, Chloroform-d) δ 163.4 k, 154.1, 143.1, 134.5 (d, J =8.6 Hz), 129.1, 127.9, 127.3, 116.5 (d, J = 3.5 Hz), 115.7 (d, J = 22.3 Hz),89.7, 82.4, 36.2.

[0195] 19 F NMR (471 MHz, Chloroform-d) δ -107.6.

[0196] High resolution: Calculated value: [M+H + ] + 254.0981, measured value: 254.0985.

[0197] Example 24:

[0198]

[0199] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodothyne 2d (114.8 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 26 as a yellow oil, with a yield of 97%.

[0200] Compound 26 was tested and found to be:

[0201] 1 H NMR (500 MHz, Chloroform-d) δ 7.45-7.41 (m, 2H), 7.39-7.36 (m,1H), 7.35-7.32 (m, 2H), 7.21-7.17 (m, 2H), 7.05-7.01 (m, 2H), 3.37 (s, 3H).

[0202] 13 C NMR (125 MHz, Chloroform-d) δ 154.0, 143.0, 136.1, 133.5, 129.1, 128.7, 127.9, 127.3, 118.8, 89.5, 83.3, 36.3.

[0203] High resolution: Calculated value: [M+H + ] + 270.0686, measured value: 270.0688.

[0204] Example 25:

[0205]

[0206] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodoacetylene 2e (111.9 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and then anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 27 as a black solid, in 63% yield.

[0207] Compound 27 was tested and found to be:

[0208] 1 H NMR (500 MHz, Chloroform-d) δ 7.53-7.50 (m, 2H), 7.47-7.42 (m,2H), 7.41-7.37 (m, 1H), 7.35-7.32 (m, 2H), 7.22-7.18 (m, 2H), 3.38 (s, 3H).

[0209] 13 C NMR (125 MHz, Chloroform-d) δ 153.4, 142.8, 132.7, 131.9, 129.2, 128.2, 127.3, 125.2, 117.9, 113.2, 88.1, 85.6, 36.4.

[0210] High resolution: Calculated value: [M+H + ] + 261.1028, measured value: 261.1031.

[0211] Example 26:

[0212]

[0213] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodoacetylene 2f (114.8 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 28 as a yellow oil, in 72% yield.

[0214] Compound 28 was tested and found to be:

[0215] 1 H NMR (500 MHz, Chloroform-d) δ 7.47-7.43 (m, 2H), 7.42-7.38 (m,1H), 7.36-7.33 (m, 2H), 7.30-7.27 (m, 1H), 7.16 (t, J = 8.0 Hz, 1H), 7.06 (t,J = 1.5 Hz, 1H), 7.02 (dt,J = 8.0, 1.5 Hz, 1H), 3.38 (s, 3H).

[0216] 13 C NMR (125 MHz, Chloroform-d) δ 153.9, 143.0, 134.1, 132.0, 130.4, 130.1, 129.5, 129.2, 128.1, 127.3, 122.1, 89.0, 83.3, 36.3.

[0217] High resolution: Calculated value: [M+H + ] + 270.0686, measured value: 270.0689.

[0218] Example 27:

[0219]

[0220] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodothyne 2 g (126.9 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 29 as a yellow oil, with a yield of 73%.

[0221] Compound 29 was tested and found to be:

[0222] 1 H NMR (500 MHz, Chloroform-d) δ 7.47-7.43 (m, 2H), 7.42-7.38 (m,1H), 7.36-7.33 (m, 2H), 7.26 (t, J = 8.0 Hz, 1H), 7.18-7.14 (m, 1H), 7.09-7.06 (m, 1H), 6.93-6.91 (m, 1H), 3.39 (s, 3H).

[0223] 13 C NMR (125 MHz, Chloroform-d) δ 153.8, 148.8(q, J = 1.9 Hz), 143.0,130.6, 129.9, 129.2, 128.1, 127.4, 124.5, 122.5, 122.2, 120.2 (q, J = 256.5Hz), 88.8, 83.4, 36.3.

[0224] 19 F NMR (471 MHz, Chloroform-d) δ -58.0.

[0225] High resolution: Calculated value: [M+H + ] + 320.0898, measured value: 320.0901.

[0226] Example 28:

[0227]

[0228] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodothyne 2h (114.8 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 30 as a yellow oil in 83% yield.

[0229] Compound 30 was tested and found to be:

[0230] 1 H NMR (500 MHz, Chloroform-d) δ 7.44-7.39 (m, 2H), 7.36-7.33 (m,3H), 7.29-7.21 (m, 3H), 7.13 (td, J = 7.5, 1.5 Hz, 1H), 3.38 (s, 3H).

[0231] 13 C NMR (125 MHz, Chloroform-d) δ 153.9, 142.9, 136.6, 134.3, 130.8, 129.3, 129.2, 127.9, 127.4, 126.3, 120.7, 87.0, 86.8, 36.5.

[0232] High resolution: Calculated value: [M+H + ] + 270.0686, measured value: 270.0688.

[0233] Example 29:

[0234]

[0235] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodothyne 2i (98.4 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The mixture was purged three times with nitrogen in a double-row tube, and then anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 31 as a white solid in 68% yield.

[0236] Compound 31 was tested and found to be:

[0237] 1H NMR (500 MHz, Chloroform-d) δ 7.42-7.37 (m, 2H), 7.35-7.31 (m,1H), 7.29-7.26 (m, 2H), 3.32 (s, 3H), 2.09 (t, J = 7.0 Hz, 2H), 1.24-1.19 (m, 2H), 1.10-1.03 (m, 2H), 0.75 (t, J = 7.0 Hz, 3H).

[0238] 13 C NMR (100 MHz, DMSO-d6) δ 153.5, 143.5, 129.5, 128.1, 127.8, 93.6,75.7, 36.3, 29.4, 21.3, 17.9, 13.8.

[0239] High resolution: Calculated value: [M+H + ] + 216.1388, measured value: 216.1390.

[0240] Example 30:

[0241]

[0242] In a dry 10 mL reaction tube, amide-substituted dihydroquinazolinone 1a (59.0 mg, 0.2 mmol), high-valent iodothyne 2j (128.5 mg, 0.3 mmol), sodium dihydrogen phosphate (48.0 mg, 4.0 mmol), and a magnetic bubbling device were added. The tube was purged three times with nitrogen in a double-row configuration, and anhydrous dichloromethane (DCM, 2 mL) was added. After irradiating the reaction tube under blue light for 16 hours, column chromatography yielded compound 32 as a yellow liquid, with a yield of 61%.

[0243] Compound 32 was tested and found to be:

[0244] 1 H NMR (500 MHz, Chloroform-d) δ 7.40-7.35 (m, 2H), 7.32-7.27 (m,3H), 3.31 (s, 3H), 0.92-0.85 (m, 21H).

[0245] 13 C NMR (125 MHz, Chloroform-d) δ 153.6, 143.3, 129.3, 127.9, 127.5, 98.6, 95.1, 36.5, 18.3, 10.8.

[0246] High resolution: Calculated value: [M+H + ] + 316.2097, measured value: 316.2099.

Claims

1. A method for synthesizing α,β-unsaturated acetylene amides directly induced by visible light, characterized in that... Includes the following steps: The dihydroquinazolinone derivative precursor 1 containing carbamoyl fragment, alkynyl high-valent iodine reagent 2, and sodium dihydrogen phosphate were added to a photoreaction tube under nitrogen atmosphere protection, anhydrous solvent was added, and the reaction was stirred under visible light irradiation. After the reaction was completed, the target product α,β-unsaturated alkynylamide 3 was obtained by conventional post-processing and separation and purification. The synthesis route is shown below: 。 2. The synthesis method according to claim 1, characterized in that: R in dihydroquinazolinone derivative precursor 1 and alkynyl hypervalent iodine reagent 2 1 R 2 and R 3 Each is independently selected from hydrogen, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C1-C20 alkoxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl; or R 1 With R 2 Forming a ring.

3. The synthesis method according to claim 1, characterized in that: The solvent is dichloromethane.

4. The synthesis method according to claim 1, characterized in that: The reaction temperature was room temperature.

5. The synthesis method according to claim 1, characterized in that: The visible light source is blue light.

6. The synthesis method according to claim 1, characterized in that: The separation and purification are carried out by recrystallization or silica gel column chromatography, with petroleum ether and ethyl acetate or dichloromethane and methanol as the eluent.

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