Azo / deuterated imidazo buprofezin compound, synthetic method and application

Abstract

The invention belongs to the field of organic synthesis methods, and discloses an azo / deuterated imidazo buprofezin compound as well as a synthesis method and application thereof. According to the method, at the room temperature, aryl diazonium tetrafluoroborate or deuterium water, acryloyl chloride and 2-mercapto benzimidazole or 2-mercapto imidazole compounds are used as raw materials, and the azo / deuterated imidazo buprofezin compounds with medical application prospects are synthesized in the air atmosphere in the presence of alkali. Compared with a previously reported preparation method, the method has the advantages of being green, environmentally friendly, safe, efficient and energy-saving, the substrate application range is wide, the product functional group compatibility is good, raw materials are easy to obtain, operation is easy and convenient, and potential industrial application prospects are achieved.

Description

Technical Field

[0001] The present invention relates to the academic field of organic synthesis methods, and more specifically to a method for synthesizing and applying an azo / dideuterated compound containing an imidazothiazinone skeleton. Background Art

[0002] Imidazothiazinone derivatives have a wide range of applications due to their superior structural advantages and biological activities, and are one of the most important nitrogen- and sulfur-containing heterocyclic compounds. Imidazothiazinone derivatives have many functions in pharmaceutical applications, such as inhibiting the activity of tuberculosis bacteria, antiviral activity, antitumor activity, etc. For example, 7,8,9-trifluoro-2,3-dihydro-5H-benzo[e]imidazo[2,1-b][1,3]thiazin-5-one and 2,4,8,9-tetrafluoro-1,3-bis(4-methylpiperidin-1-yl)-12H-benzo[e]benzo[4,5]imidazo[2,1-b][1,3]thiazin-5-one have good anti-tuberculosis bacterial activity; 1,3-dimethyl-6H-benzo[5,6][1,3]thiazino[2,3-f]purine-2,4,6-(1H,3H)-trione and 9,10,11,12-tetrafluoro-13H-benzo[5,6][1,3]thiazino[3,2-a]purin-13-one have excellent antitumor activity; N-(4-(benzofuran-2-yl))benzyl)-4-oxo-3,4-dihydro-2H-imidazo[5,1-b][1,3]thiazine-3-carboxamide can be used as an ALK inhibitor; 4-oxo-N-(thiazol-2-yl)-3,4-dihydro-1H-benzo[4,5]imidazo[2,1-c][1,4]thiazine-8-carboxamide has good anti-HSV-1 activity; (Z)-2-(3-((4-chlorobenzyl)oxy)benzylidene)-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3(2H)-one is a good GPR18 antagonist.

[0003] Due to the importance of imidazothiazinone derivatives, numerous synthesis methods have been developed. The synthesis methods mainly use transition metal catalysts (such as copper, palladium, iron, etc.) under high-temperature reaction conditions (110°C, 130°C) or use expensive NHC reagents at room temperature. These synthesis methods have relatively harsh reaction conditions and high reaction risks.

[0004] Therefore, developing a method for green and efficient synthesis of imidazothiazinone derivatives without using transition metal catalysts and oxidants under mild reaction conditions will be a more attractive and challenging goal.

[0005] Azo compounds are an important class of organic compounds, which widely exist in natural products, drugs, agrochemicals, functional materials and the field of synthesis. Generally, the reactions for synthesizing azo compounds include diazo coupling reaction, Mills reaction, Wallach reaction, and the reduction coupling reaction of aromatic nitro compounds, oxidation reaction of aniline, dehydrogenation reaction of aromatic hydrazine, dimerization reaction of diazonium salts and rearrangement reaction of triazene developed in recent years. At present, the most commonly used method is to diazotize aromatic primary amines at low temperature first and then react with nucleophiles to synthesize azo compounds. However, this reaction is sensitive to temperature, which to a certain extent limits the practical application of this synthesis strategy. Aryl diazonium tetrafluoroborate has become one of the most commonly used azoating reagents because its raw materials are easily available and the preparation is simple.

[0006] Deuterium is an isotope of hydrogen and only differs from hydrogen by one neutron. Its abundance on the earth is 0.015%, and most of it exists in seawater and ordinary water in the form of heavy water. Deuterated compounds refer to new compounds obtained by replacing hydrogen atoms in compounds with their isotope deuterium. They are a class of chemicals with high added value and show good application prospects in the fields of biological metabolism analysis, nuclear magnetic resonance, intermediate labeling, pollution source tracking, etc. Deuterium water has become one of the most commonly used deuterated reagents because it is relatively cheap and has a low cost.

[0007] However, in the previous methods for synthesizing imidazothiazinone compounds, most of them need to add transition metal catalysts (such as silver, gold, chromium, copper, iridium, etc.) or be carried out under high-temperature reaction (110 °C, 130 °C) conditions or photocatalytic conditions. These synthesis methods have relatively harsh reaction conditions and require specific reaction vessels, which are not conducive to large-scale preparation.

[0008] Therefore, it is an urgent problem for those skilled in the art to study a method for efficiently, greenly and environmentally friendly preparing azoated / deuterated imidazothiazinone compounds and being easy to scale up. Summary of the Invention

[0009] Aiming at the above problems, the purpose of the present invention is to provide a method for simply and conveniently preparing azoated / deuterated imidazothiazinone compounds by using a room-temperature reaction, and synthesizing azoated / deuterated imidazothiazinone through aryl diazonium tetrafluoroborate / deuterium water, acryloyl chloride and 2-mercaptoimidazole or 2-mercaptobenzimidazole compounds. This method does not require a metal catalyst, nor does it need to add an oxidant or a reductant. It has the advantages of energy conservation, environmental protection, easily available raw materials, mild and safe reaction conditions, simple reaction device, wide adaptability, etc.

[0010] One of the purposes of the present invention is to provide a class of azoated / deuterated imidazothiazinone compounds, and its chemical structural formula is:

[0011]

[0012] Wherein,

[0013] R 1 is a phenylazo group, naphthylazo group, benzo[d][1,3]dioxolyl group, benzothiazolyl group, substituted phenylazo group or deuterium atom;

[0014] R 2 is phenyl or substituted phenyl.

[0015] Preferably, in R 1 , the substituent of the substituted phenylazo group is one of methyl, isopropyl, tert-butyl, trifluoromethyl, benzyl, ethoxy or halogen atom, and the number of substituents is 1 or 2; in R 2 , the substituent of the substituted phenyl is one of methyl, ethoxy or halogen atom, and the number of substituents is 1 or 2.

[0016] More preferably, the halogen atom in the R 1 is selected from one of fluorine atom, chlorine atom, bromine atom and iodine atom; the halogen atom in the R 2 is selected from fluorine atom or bromine atom.

[0017] The second object of the present invention is to provide a method for synthesizing azo / diazotized imidazo[2,1-b][1,3]thiazin-4(3H)-one compounds, and the synthesis route is as follows:

[0018]

[0019] Under room temperature conditions, using aryl diazonium tetrafluoroborate / deuterium water as raw materials, adding reaction base, reacting with acryloyl chloride 3 and 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives 4 to generate azo / diazotized imidazo[2,1-b][1,3]thiazin-4(3H)-one compounds 1. Among them, the aryl diazonium tetrafluoroborate in the synthesis route can be replaced by deuterium water.

[0020] The reaction mechanism of the present invention is as follows: First, under the action of cesium carbonate, 2-mercaptobenzimidazole compounds or 2-mercaptoimidazole compounds 4 react with acryloyl chloride 3 to generate a sulfur anion intermediate, and then an intramolecular cyclization reaction occurs to generate a carbanion intermediate B. After that, intermediate B reacts with aryl diazonium tetrafluoroborate / deuterium water to generate azo / diazotized imidazo[2,1-b][1,3]thiazin-4(3H)-one compounds.

[0021] Furthermore, the synthesis method is as follows:

[0022] At room temperature, in a Schlenk reaction tube, aryl diazonium tetrafluoroborate or deuterium water, acryloyl chloride, 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives, base and reaction solvent are added in sequence, and the reaction is carried out in an air atmosphere for 3-5 h; after the reaction is completed, volatile components are removed under reduced pressure, and then the product is separated and characterized by silica gel column chromatography to obtain azo / diazotized imidazo[2,1-b][1,3]thiazin-4(3H)-one compounds.

[0023] Preferably, the molar ratio of the aromatic diazo tetrafluoroborate, acryloyl chloride, 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives, and the base is 0.1:0.2:0.2:0.1;

[0024] The molar ratio of deuterated water, acryloyl chloride, 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives, and base is 2:0.2:0.2:0.1.

[0025] Preferably, the reaction solvent is one of N,N-dimethylformamide, 1,2-dichloroethane, and acetonitrile; the base is one of pyridine, cesium carbonate, potassium tert-butoxide, and triethylamine; and the concentration of the base in the reaction solvent is 0.025 mmol / mL.

[0026] Further preferably, the solvent is acetonitrile, the base is cesium carbonate, and the optimal reaction time is 4 hours.

[0027] The role of the base in the reaction is to use the alkalinity of cesium carbonate to remove hydrogen from NH and SH to generate corresponding negative ions.

[0028] Preferably, the reaction temperature is 10-50°C, and the optimal reaction temperature is 25°C.

[0029] The third object of the present invention is to provide an application of an azo / deuterated imidazothiazinone compound.

[0030] The imidazothiazinone skeleton, azo structure and deuterium atom of the synthesized azo / deuterated imidazothiazinone compounds are important components of many drugs. Therefore, based on the existing research results, it is reasonable to speculate that the synthesized azo / deuterated imidazothiazinone compounds have excellent medical prospects and can be used as important pharmaceutical intermediates.

[0031] It can be seen from the above technical solution that, compared with the prior art, the beneficial effects achieved by the present invention are:

[0032] 1) High efficiency: the synthesis method has short reaction time and high yield;

[0033] 2) Environmental protection: The room temperature method is used, and no catalyst or oxidant is required, which reduces environmental harm;

[0034] 3) Easy to scale up: The reaction device is simple and easy to realize industrial production;

[0035] 4) Mild conditions: The reaction conditions are mild, without the need for harsh conditions such as high temperature and high pressure;

[0036] 5) Raw materials are readily available: The raw materials used are easily available and inexpensive;

[0037] 6) Simple operation: The operation is simple and easy to realize laboratory and industrial production.

[0038] In summary, this method does not require the addition of any oxidizing agent or reducing agent, has mild conditions, is energy-saving and environmentally friendly, the raw materials are cheap and easily available, the operation is simple, safe and reliable, easy to scale up for preparation, and the product yield is relatively high. Specific implementation mode

[0039] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0040] Example 1

[0041]

[0042] In a 10 mL Schlenk reaction tube, phenyl diazonium tetrafluoroborate 5 (19.2 mg, 0.1 mmol), methacryloyl chloride 6 (21.0 μL, 0.2 mmol), 2-mercaptobenzimidazole 7 (30.0 mg, 0.2 mmol), cesium carbonate (32.6 mg, 0.1 mmol) and 4 mL of acetonitrile were added in sequence. The reaction tube was stirred at room temperature of 25 °C for 4 h. After the reaction was completed, the volatile components were removed under reduced pressure, and then separated by silica gel column chromatography (the eluent was petroleum ether (60 - 90 °C) / ethyl acetate, v / v = 3:1) to obtain the target product 8 (28.7 mg, yield 89%) as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0043] 3-Methyl-3-(phenyldiazenyl)-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (8): New compound, 28.5 mg, 89% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.30 - 8.29 (m, 1H), 7.63 - 7.59 (m, 3H), 7.45 - 7.30 (m, 3H), 7.37 - 7.32 (m, 2H), 3.88 (d, J = 13.9 Hz, 1H), 3.78 (d, J = 13.8 Hz, 1H), 1.90 (s, 3H). 13 CNMR(CDCl 3, 150 MHz) δ 167.7, 151.0, 150.1, 143.2, 132.9, 132.0, 129.2, 125.7, 124.7, 122.8, 118.7, 115.7, 74.5, 34.8, 21.4. HRMS(ESI) m / z Calcd for C 17 H 15 N 4 OS[M + H] + : 323.0961; Found: 323.0961.

[0044] Example 2

[0045] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that the reaction solvent was replaced with methanol. The reaction was stopped, and the target product 8 (3.0 mg, yield 9%) was obtained after post-treatment. It shows that changing the solvent is not conducive to the reaction.

[0046] Example 3

[0047] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that the reaction time was 3 h. The reaction was stopped, and the target product 8 (15.1 mg, yield 47%) was obtained after post-treatment. It shows that reducing the time is not conducive to the reaction.

[0048] Example 4

[0049] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that cesium carbonate was not added during the reaction. The reaction was stopped, and the target product 8 (9.0 mg, yield 28%) was obtained after post-treatment. It shows that not adding a base is not conducive to the reaction.

[0050] Example 5

[0051] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that the reaction base was replaced with triethylamine. The reaction was stopped, and the target product 8 (13.5 mg, yield 42%) was obtained after post-treatment. It shows that changing the base is not conducive to the reaction.

[0052] Example 6

[0053]

[0054] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 3 - tolyldiazonium tetrafluoroborate 9 (20.6 mg, 0.1 mmol) was added to the reaction system. After post-treatment, the target product 10 (26.7 mg, yield 79%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0055] 3-Methyl-3-(m-tolyldiazenyl)-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (10): New compound, 26.7 mg, 79% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.30 - 8.29 (m, 1H), 7.60 - 7.59 (m, 1H), 7.43 - 7.41 (m, 2H), 7.37 - 7.32 (m, 2H), 7.31 - 7.28 (m, 1H), 7.26 - 7.24 (m, 1H), 3.87 (d, J=13.8 Hz, 1H), 3.77 (d, J=13.8 Hz, 1H), 2.36 (s, 3H), 1.89 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.7, 151.1, 150.2, 143.2, 139.2, 132.9, 132.7, 129.0, 125.7, 124.7, 123.2, 120.2, 118.7, 115.7, 74.4, 34.8, 21.4, 21.3. HRMS(ESI) m / z Calcd for C 18 H 17 N 4 OS[M + H] + : 337.1118; Found: 337.1111.

[0056] Example 7

[0057]

[0058] The reaction steps and operations were the same as in Example 1, except that 4 - tolyldiazonium tetrafluoroborate 11 (20.6 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post - treatment, the target product 12 (28.3 mg, yield 84%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high - resolution mass spectrometry.

[0059] 3 - Methyl - 3-(p - tolyldiazenyl)-2,3 - dihydro - 4H - benzo[4,5]imidazo[2,1 - b][1,3]thiazin - 4 - one (12): New compound, 28.3 mg, 84% yield. Pale yellow oil. 1 HNMR(CDCl 3, 600 MHz) δ 8.30 - 8.28 (m, 1H), 7.60 - 7.58 (m, 1H), 7.53 - 7.51 (m, 2H), 7.37 - 7.31 (m, 2H), 7.20 (d, J = 8.3 Hz, 2H), 3.85 (d, J = 13.7 Hz, 1H), 3.76 (d, J = 13.8 Hz, 1H), 2.37 (s, 3H), 1.88 (s, 3H). 13 C NMR (CDCl 3 , 150 MHz) δ 167.8, 150.3, 149.1, 143.1, 142.7, 132.9, 129.8, 125.7, 124.7, 122.9, 118.6, 115.7, 74.2, 34.8, 21.6, 21.4. HRMS (ESI) m / z Calcd for C 18 H 17 N 4 OS [M + H] + : 337.1118;

[0060] Found: 337.1111.

[0061] Example 8

[0062]

[0063] The reaction steps and operations were the same as in Example 1, except that 4 - isopropylphenyldiazonium tetrafluoroborate 13 (23.4 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post - treatment, the target product 14 (33.3 mg, yield 91%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high - resolution mass spectrometry.

[0064] 3 - ((4 - Isopropylphenyl)diazenyl)-3 - methyl - 2,3 - dihydro - 4H - benzo[4,5]imidazo[2,1 - b][1,3]thiazin - 4 - one (14): New compound, 33.3 mg, 91% yield. Pale yellow oil. 1 H NMR (CDCl 3, 600 MHz) δ 8.30 - 8.28 (m, 1H), 7.59 - 7.56 (m, 3H), 7.36 - 7.31 (m, 2H), 7.27 - 7.25 (m, 2H), 3.86 (d, J = 13.7 Hz, 1H), 3.76 (d, J = 13.8 Hz, 1H), 2.92 (p, J = 6.8 Hz, 1H), 1.87 (s, 3H), 1.24 (d, J = 6.9 Hz, 6H). 13 C NMR (CDCl 3 , 150 MHz) δ 167.8, 153.5, 150.2, 149.3, 143.2, 132.9, 127.2, 125.6, 124.7, 123.0, 118.6, 115.6, 74.2, 34.8, 34.2, 23.9, 21.4. HRMS (ESI) m / z Calcd for C 20 H 21 N 4 OS [M + H] + : 365.1431; Found: 365.1422.

[0065] Example 9

[0066]

[0067] The reaction steps and operations were the same as in Example 1, except that 4-tert-butylphenyl diazonium tetrafluoroborate 15 (24.8 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and the target product 16 (28.3 mg, yield 75%) was obtained after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0068] 3-((4-(tert-Butyl)phenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (16): New compound, 28.3 mg, 75% yield. Pale yellow oil. 1 H NMR (CDCl 3 , 600 MHz) δ 8.30 - 8.29 (m, 1H), 7.60 - 7.56 (m, 3H), 7.44 - 7.42 (m, 2H), 7.36 - 7.31 (m, 2H), 3.87 (d, J = 13.8 Hz, 1H), 3.77 (d, J = 13.8 Hz, 1H), 1.88 (s, 3H), 1.31 (s, 9H). 13 C NMR (CDCl3 , 150 MHz) δ 167.8, 155.7, 150.2, 148.9, 143.2, 132.9, 126.1, 125.6, 124.7, 122.6, 118.6, 115.7, 74.2, 35.1, 34.8, 31.3, 21.4. HRMS(ESI) m / z Calcd for C 21 H 23 N 4 OS [M + H] + : 379.1587; Found: 379.1594.

[0069] Example 10

[0070]

[0071] The reaction steps and operations were the same as in Example 1, except that 4-ethoxyphenyldiazonium tetrafluoroborate 17 (23.6 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 18 (31.4 mg, yield 86%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0072] 3-((4-Ethoxyphenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (18): New compound, 31.4 mg, 86% yield. Pale yellow oil. 1 1H NMR (CDCl 3 , 600 MHz) δ 8.30 - 8.28 (m, 1H), 7.61 - 7.58 (m, 3H), 7.36 - 7.31 (m, 2H), 6.88 - 6.85 (m, 2H), 4.05 (q, J = 7.0 Hz, 2H), 3.82 (d, J = 13.7 Hz, 1H), 3.74 (d, J = 13.8 Hz, 1H), 1.86 (s, 3H), 1.41 (t, J = 7.0 Hz, 3H). 13 13C NMR (CDCl 3 , 150 MHz) δ 168.1, 162.2, 150.4, 145.0, 143.2, 132.9, 125.6, 124.9, 124.6, 118.6, 115.7, 114.6, 73.8, 64.0, 34.9, 21.5, 14.8. HRMS(ESI) m / z Calcd for C 19 H 19 N4 O 2 S[M+H] + : 367.1223; Found: 367.1215.

[0073] Example 11

[0074]

[0075] The reaction steps and operations were the same as those in Example 1, except that 4-fluorophenyl diazonium tetrafluoroborate 19 (21.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 20 (30.0 mg, yield 88%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0076] 3-((4-Fluorophenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (20): New compound, 30.0 mg, 88% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.33 - 8.27 (m, 1H), 7.66 - 7.63 (m, 2H), 7.60 - 7.58 (m, 1H), 7.337 - 7.31 (m, 2H), 7.10 - 7.07 (m, 2H), 3.85 (d, J = 13.7 Hz, 1H), 3.77 (d, J = 13.8 Hz, 1H), 1.88 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.5, 164.9 (d, J =

[0077] 252.0 Hz), 150.1, 147.4 (d, J = 3.0 Hz), 143.2, 132.8, 125.7, 125.1 (d, J = 9.0 Hz), 124.8, 118.7, 116.2, 116.1, 115.7, 74.4, 34.8, 21.4. 19 FNMR(565 MHz, CDCl 3 ) δ: 29.7. HRMS(ESI) m / z Calcd for C 17 H 14 FN 4 OS[M+H] + : 341.0867; Found: 341.0862.

[0078] Example 12

[0079]

[0080] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 3-chlorophenyldiazonium tetrafluoroborate 21 (22.6 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 22 (21.5 mg, yield 60%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0081] 3-((3-Chlorophenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (22): New compound, 21.5 mg, 60% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.29 - 8.27 (m, 1H), 7.62 - 7.59 (m, 2H), 7.54 - 7.52 (m, 1H), 7.43 - 7.41 (m, 1H), 7.37 - 7.34 (m, 3H), 3.88 (d, J = 13.9 Hz, 1H), 3.79 (d, J = 13.9 Hz, 1H), 1.90 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.3, 151.7, 149.9, 143.1, 135.3, 132.8, 131.8, 130.3, 125.8, 124.9, 122.4, 121.9, 118.7, 115.7, 74.8, 34.8, 21.4. HRMS(ESI) m / z Calcd for C 17 H 14 ClN 4 OS[M + H] + : 357.0571; Found: 357.0563.

[0082] Example 13

[0083]

[0084] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 4-chlorophenyl diazonium tetrafluoroborate 23 (22.6 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 24 (20.7 mg, yield 58%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0085] 3-((4-Chlorophenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (24): New compound, 20.7 mg, 58% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.29 - 8.27 (m, 1H), 7.60 - 7.56 (m, 3H), 7.40 - 7.37 (m, 2H), 7.35 (td, J = 7.3, 1.5 Hz, 2H), 3.86 (d, J = 13.8 Hz, 1H), 3.77 (d, J = 13.8 Hz, 1H), 1.89 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.4, 150.0, 149.3, 143.2, 138.2, 132.8, 129.5, 129.3, 125.8, 124.8, 124.2, 124.0, 118.7, 115.7, 74.6, 34.8, 21.4. HRMS(ESI) m / z Calcd for C 17 H 14 ClN 4 OS[M + H] + : 357.0571; Found: 357.0563.

[0086] Example 14

[0087]

[0088] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 3-bromophenyl diazonium tetrafluoroborate 25 (27.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 26 (17.6 mg, yield 44%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0089] 3-((3-Bromophenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (26): New compound, 17.6 mg, 44% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.29 - 8.27 (m, 1H), 7.77 (t, J = 2.0 Hz, 1H), 7.59 - 7.56 (m, 3H), 7.36 - 7.34 (m, 2H), 7.30 (d, J = 8.0 Hz, 1H), 3.88 (d, J = 13.9 Hz, 1H), 3.78 (d, J = 13.9 Hz, 1H), 1.90 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ

[0090] 167.3, 151.7, 150.0, 143.0, 134.7, 132.8, 130.6, 125.8, 124.9, 124.7, 123.2, 122.9, 118.7, 115.7, 74.8, 34.8, 21.4. HRMS(ESI) m / z Calcd for C 17 H 14 BrN 4 OS[M + H] + : 401.0066; Found: 401.0057.

[0091] Example 15

[0092]

[0093] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 4-bromophenyl diazonium tetrafluoroborate 27 (27.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and the target product 28 (20.8 mg, yield 52%) was obtained as a pale yellow liquid after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0094] 3-((4-Bromophenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (28): New compound, 20.8 mg, 52% yield. Pale yellow oil. 1HNMR(CDCl 3 , 600 MHz) δ 8.29 - 8.27 (m, 1H), 7.60 - 7.59 (m, 1H), 7.56 - 7.54 (m, 2H), 7.51 - 7.49 (m, 2H), 7.37 - 7.32 (m, 2H), 3.86 (d, J=13.9 Hz, 1H), 3.77 (d, J=13.9 Hz, 1H), 1.89 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.4, 150.0, 149.6, 143.2, 132.8, 132.5, 132.3, 126.7, 125.8, 124.8, 124.4, 118.7, 115.7, 74.7, 34.8, 21.4. HRMS(ESI) m / z Calcd for C 17 H 14 BrN 4 OS[M + H] + : 401.0066; Found: 401.0059.

[0095] Example 16

[0096]

[0097] The reaction steps and operations were the same as in Example 1, except that 3 - iodophenyl diazonium tetrafluoroborate 29 (31.8 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post - treatment, the target product 30 (27.9 mg, yield 65%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high - resolution mass spectrometry.

[0098] 3 - ((3 - iodophenyl)diazenyl)-3 - methyl - 2,3 - dihydro - 4H - benzo[4,5]imidazo[2,1 - b][1,3]thiazin - 4 - one (30): New compound, 27.9 mg, 65% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.28 - 8.27 (m, 1H), 7.95 (t, J=1.7 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.61 - 7.59 (m, 2H), 7.37 - 7.32 (m, 2H), 7.15 (t, J=7.9 Hz, 1H), 3.87 (d, J=13.8 Hz, 1H), 3.78 (d, J=13.9 Hz, 1H), 1.90 (s, 3H).13 CNMR (CDCl 3 , 150 MHz) δ 167.3, 151.6, 149.9, 143.1, 140.6, 132.8, 130.6, 125.8, 124.8, 123.5, 118.7, 115.7, 74.8, 34.8, 21.4. HRMS (ESI) m / z Calcd for C 17 H 14 IN 4 OS[M + H] + : 448.9928; Found: 448.9933.

[0099] Example 17

[0100]

[0101] The reaction steps and operations were the same as those in Example 1, except that 4-iodophenyl diazonium tetrafluoroborate 31 (31.8 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 32 (22.2 mg, yield 50%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0102] 3-((4-Iodophenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (32): New compound, 22.2 mg, 50% yield. Pale yellow oil. 1 HNMR (CDCl 3 , 600 MHz) δ 8.29 - 8.27 (m, 1H), 7.78 - 7.76 (m, 2H), 7.59 - 7.58 (m, 1H), 7.37 - 7.32 (m, 4H), 3.86 (d, J = 13.9 Hz, 1H), 3.77 (d, J = 13.9 Hz, 1H), 1.89 (s, 3H). 13 CNMR (CDCl 3 , 150 MHz) δ 167.4, 150.2, 150.0, 143.2, 139.0, 138.5, 134.4, 132.8, 125.8, 124.8, 124.4, 118.7, 115.7, 99.1, 74.7, 34.8, 21.4. HRMS (ESI) m / z Calcd for C 17 H 14 IN 4 OS[M + H]+ : 448.9928; Found: 448.9919.

[0103] Example 18

[0104]

[0105] The reaction steps and operations were the same as those in Example 1, except that 4-(trifluoromethyl)phenyl diazonium tetrafluoroborate 33 (26.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and the target product 34 (22.3 mg, yield 57%) was obtained as a pale yellow liquid after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0106] 3-Methyl-3-((4-(trifluoromethyl)phenyl)diazenyl)-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (34): New compound, 22.3 mg, 57% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.29 - 8.28 (m, 1H), 7.70 (q, J = 8.6 Hz, 4H), 7.60 - 7.59 (m, 1H), 7.38 - 7.33 (m, 2H), 3.90 (d, J = 14.0 Hz, 1H), 3.80 (d, J = 13.9 Hz, 1H), 1.93 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.1, 152.7, 149.8, 143.2, 133.4 (q, J = 31.5 Hz), 132.8, 126.4 (q, J = 4.5 Hz), 125.9, 124.9, 123.7 (q, J = 270.0 Hz), 123.1, 118.8, 115.7, 75.1, 34.7, 21.4. 19 FNMR(565 MHz, CDCl 3 ) δ: 15.1. HRMS(ESI) m / z Calcd for C 18 H 14 F 3 N 4 OS[M + H] + : 391.0835; Found: 391.0828.

[0107] Example 19

[0108]

[0109] The reaction steps and operations were the same as those in Example 1, except that 2-benzylphenyl diazonium tetrafluoroborate 35 (28.2 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 36 (27.6 mg, yield 67%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0110] 3-((2-Benzylphenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (36): New compound, 27.6 mg, 67% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.24 (d, J = 7.9 Hz, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.31 - 7.27 (m, 2H), 7.26 - 7.23 (m, 2H), 7.04 - 7.03 (m, 3H), 6.83 - 6.82 (m, 2H), 4.00 (d, J = 6.1 Hz, 2H), 3.82 (d, J = 13.7 Hz, 1H), 3.74 (d, J = 13.8 Hz, 1H), 1.84 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.8, 149.9, 148.6, 143.1, 140.7, 140.6, 132.8, 132.3, 131.2, 129.0, 128.6, 128.4, 128.3, 127.2, 125.9, 125.6, 124.8, 118.7, 115.8, 115.5, 74.8, 36.5, 34.7, 21.4. HRMS(ESI) m / z Calcd for C 24 H 21 N 4 OS[M + H] + : 413.1431; Found: 413.1424.

[0111] Example 20

[0112]

[0113] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 4-benzylphenyl diazonium tetrafluoroborate 37 (28.2 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 38 (34.1 mg, yield 83%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0114] 3-((4-Benzylphenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (38): New compound, 34.1 mg, 83% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.29 - 8.27 (m, 1H), 7.59 - 7.57 (m, 1H), 7.55 - 7.53 (m, 2H), 7.35 - 7.30 (m, 2H), 7.27 - 7.25 (m, 2H), 7.22 - 7.17 (m, 3H), 7.13 (d, J = 7.1 Hz, 2H), 3.98 (s, 2H), 3.84 (d, J = 13.7 Hz, 1H), 3.74 (d, J = 13.8 Hz, 1H), 1.86 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.7, 150.2, 149.4, 145.6, 143.2, 140.3, 132.9, 129.7, 129.0, 128.7, 126.5, 125.7, 124.7, 123.1, 118.6, 115.7, 74.3, 41.8, 34.8, 21.4. HRMS(ESI) m / z Calcd for C 24 H 21 N 4 OS[M + H] + : 413.1431; Found: 413.1422.

[0115] Example 21

[0116]

[0117] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 3,4-dimethylphenyl diazonium tetrafluoroborate 39 (22.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 40 (32.8 mg, yield 94%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0118] 3-((3,4-Dimethylphenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (40): New compound, 32.8 mg, 94% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.31 - 8.29 (m, 1H), 7.60 - 7.58 (m, 1H), 7.40 - 7.40 (m, 1H), 7.37 - 7.31 (m, 3H), 7.15 (d, J = 8.0 Hz, 1H), 3.85 (d, J = 13.8 Hz, 1H), 3.76 (d, J = 13.8 Hz, 1H), 2.27 (s, 3H), 2.26 (s, 3H), 1.87 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.9, 150.3, 149.4, 143.2, 141.4, 137.6, 132.9, 130.2, 125.6, 124.7, 123.7, 120.7, 118.6, 115.7, 74.2, 34.9, 21.4, 20.0, 19.8. HRMS(ESI) m / z Calcd for C 19 H 19 N 4 OS[M + H] + : 351.1274; Found: 351.1262.

[0119] Example 22

[0120]

[0121] The reaction steps and operations were the same as those in Example 1, except that 3,5-dimethylphenyl diazonium tetrafluoroborate 41 (22.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 42 (12.4 mg, yield 35%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0122] 3-((3,5-Dimethylphenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imida zo[2,1-b][1,3]thiazin-4-one(42): New compound, 12.4 mg, 35% yield. Pale yellow oil. 1 HNMR(CDCl 3 , 600 MHz) δ 8.31 - 8.29(m, 1H), 7.60 - 7.59(m, 1H), 7.37 - 7.32(m, 2H), 7.23(s, 2H), 7.08(s, 1H), 3.86(d, J=13.8 Hz, 1H), 3.77(d, J=13.8 Hz, 1H), 2.32(s, 6H), 1.88(s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.8, 151.2, 150.2, 143.2, 139.0, 133.6, 132.9, 125.7, 124.7, 120.6, 118.7, 115.7, 74.4, 34.8, 21.4, 21.2. HRMS(ESI) m / z Calcd for C 19 H 19 N 4 OS[M + H] + : 351.1274;Found: 351.1269.

[0123] Example 23

[0124]

[0125] The reaction steps and operations were the same as in Example 1, except that 2,6-dimethylphenyl diazonium tetrafluoroborate 43 (22.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 44 (12.4 mg, yield 35%) as a pale yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0126] 3-((2,6-Dimethylphenyl)diazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imida zo[2,1-b][1,3]thiazin-4-one(44): New compound, 12.4 mg, 35% yield. Pale yellow oil. 1 HNMR(CDCl 3, 600 MHz) δ 8.27 - 8.26 (m, 1H), 7.60 - 7.59 (m, 1H), 7.36 - 7.30 (m, 2H), 7.09 (t, J = 7.7 Hz, 1H), 6.99 (d, J = 7.6 Hz, 2H), 3.91 - 3.84 (m, 2H), 2.05 (s, 6H), 1.96 (s, 3H). 13 C NMR(CDCl 3 , 150 MHz) δ 167.9, 150.0, 149.3, 143.2, 132.8, 130.8, 129.3, 129.2, 125.7, 124.8, 118.7, 115.5, 76.0, 34.3, 21.7, 18.6. HRMS(ESI) m / z Calcd for C 19 H 19 N 4 OS[M + H] + : 351.1274; Found: 351.1268.

[0127] Example 24

[0128]

[0129] The reaction steps and operations were the same as in Example 1, except that 1-naphthyldiazonium tetrafluoroborate 45 (24.2 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product 46 (40.2 mg, yield 95%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0130] 3-Methyl-3-(naphthalen-1-yldiazenyl)-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (46): New compound, 40.2 mg, 95% yield. Pale yellow oil. 1 H NMR(CDCl 3, 600 MHz) δ 8.37 - 8.35 (m, 1H), 8.01 (dd, J = 8.5, 1.1 Hz, 1H), 7.94 - 7.93 (m, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.62 - 7.60 (m, 1H), 7.55 (dd, J = 7.5, 1.3 Hz, 1H), 7.48 - 7.44 (m, 2H), 7.38 - 7.36 (m, 2H), 7.34 - 7.3 (m, 1H), 3.97 (d, J = 13.8 Hz, 1H), 3.85 (d, J = 13.9 Hz, 1H), 1.98 (s, 3H). 13 CNMR(CDCl 3 , 150 MHz) δ 167.9, 150.1, 146.2, 143.3, 134.1, 132.9, 132.3, 130.5, 127.9, 127.4, 126.7, 125.7, 125.3, 124.8, 122.7, 118.7, 115.6, 112.5, 75.1, 34.6, 21.4. HRMS(ESI) m / z Calcd for C 21 H 17 N 4 OS[M + H] + : 373.1118; Found: 373.1111.

[0131] Example 25

[0132]

[0133] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that 1 - benzo[d][1,3]dioxol - 2 - diazonium tetrafluoroborate 47 (23.6 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post - treatment, the target product 48 (17.6 mg, yield 75%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high - resolution mass spectrometry.

[0134] 3 - (Benzo[d][1,3]dioxol - 5 - yldiazenyl) - 3 - methyl - 2,3 - dihydro - 4H - benzo[4,5]imidazo[2,1 - b][1,3]thiazin - 4 - one (48): New compound, 17.6 mg, 75% yield. Pale yellow oil. 1 HNMR(CDCl 3, 600 MHz) δ 8.29 - 8.28 (m, 1H), 7.60 - 7.58 (m, 1H), 7.36 - 7.31 (m, 2H), 7.26 - 7.24 (m, 1H), 7.15 (d, J=1.9 Hz, 1H), 6.80 (d, J=8.2 Hz, 1H), 6.01 (s, 2H), 3.82 (d, J=13.7 Hz, 1H), 3.75 (d, J=13.8 Hz, 1H), 1.86 (s, 3H). 13 C NMR (CDCl 3 , 150 MHz) δ 167.9, 151.1, 150.3, 148.8, 146.6, 143.2, 132.9, 125.7, 124.7, 124.2, 118.7, 115.7, 107.9, 102.3, 98.9, 73.8, 34.9, 21.5. HRMS (ESI) m / z Calcd for C 18 H 15 N 4 O 3 S [M + H] + : 367.0860; Found: 367.0853.

[0135] Example 26

[0136]

[0137] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that benzothiazol-5-yl-diazonium tetrafluoroborate 49 (24.9 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and the target product 50 (31.5 mg, yield 83%) was obtained as a pale yellow liquid after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0138] 3-(benzo[d]thiazol-6-yldiazenyl)-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one (50): New compound, 31.5 mg, 83% yield. Pale yellow oil. 1 H NMR (CDCl 3, 600 MHz) δ 9.04 (s, 1H), 8.37 (d, J = 1.7 Hz, 1H), 8.31 - 8.30 (m, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.75 (dd, J = 8.6, 1.8 Hz, 1H), 7.60 - 7.59 (m, 1H), 7.37 - 7.32 (m, 2H), 3.91 (d, J = 13.8 Hz, 1H), 3.80 (d, J = 13.9 Hz, 1H), 1.93 (s, 3H). 13 C NMR (CDCl 3 , 150 MHz) δ 167.6, 156.0, 153.7, 150.1, 149.8, 143.1, 137.3, 132.8, 125.8, 124.8, 122.3, 119.5, 119.1, 118.7, 115.7, 74.6, 34.8, 21.4. HRMS (ESI) m / z Calcd for C 18 H 14 N 5 OS 2 [M + H] + : 380.0635; Found: 380.0634.

[0139] Example 27

[0140]

[0141] The reaction steps and operations were the same as in Example 1, except that 3,4 - dimethyl - 1H - benzimidazole - 2 - thiol 51 (35.6 mg, 0.2 mmol) was added to the reaction system. The reaction was stopped, and after post - treatment, the target product 52 (24.3 mg, yield 69%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high - resolution mass spectrometry.

[0142] 3,7,8 - Trimethyl - 3 - (phenyldiazenyl) - 2,3 - dihydro - 4H - benzo[4,5]imidazo[2,1 - b][1,3]thiazin - 4 - one (52): New compound, 24.3 mg, 69% yield. Pale yellow oil. 1 H NMR (CDCl 3, 600 MHz) δ 8.07 (s, 1H), 7.62 - 7.61 (m, 2H), 7.45 - 7.39 (m, 3H), 7.34 (s, 1H), 3.85 (d, J=13.9 Hz, 1H), 3.75 (d, J=13.8 Hz, 1H), 2.38 (s, 3H), 2.35 (s, 3H), 1.88 (s, 3H). 13 C NMR (CDCl 3 , 150 MHz) δ 167.6, 151.0, 148.9, 141.6, 134.5, 133.7, 131.9, 131.2, 129.1, 122.8, 119.0, 116.1, 74.5, 34.9, 21.4, 20.5, 20.4. HRMS (ESI) m / z Calcd for C 19 H 19 N 4 OS [M + H] + : 351.1274; Found: 351.1268.

[0143] Example 28

[0144]

[0145] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that 3,4 - difluoro - 1H - benzimidazole - 2 - thiol 53 (37.2 mg, 0.2 mmol) was added to the reaction system. The reaction was stopped, and after post - treatment, the target product 54 (27.6 mg, yield 77%) was obtained as a pale yellow liquid. The target product was confirmed by nuclear magnetic resonance spectroscopy and high - resolution mass spectrometry.

[0146] 7,8 - Difluoro - 3 - methyl - 3 - (phenyldiazenyl) - 2,3 - dihydro - 4H - benzo[4,5]imidazo[2,1 - b][1,3]thiazin - 4 - one (54): New compound, 27.6 mg, 77% yield. Pale yellow oil. 1 H NMR (CDCl 3 , 600 MHz) δ 8.15 (dd, J=10.1, 7.3 Hz, 1H), 7.62 - 7.60 (m, 2H), 7.47 - 7.41 (m, 3H), 7.36 (dd, J=9.9, 7.1 Hz, 1H), 3.89 (d, J=13.7 Hz, 1H), 3.81 (d, J=13.9 Hz, 1H), 1.89 (s, 3H). 13 C NMR (CDCl 3, 150 MHz) δ 167.5, 151.4 (d, J = 3.0 Hz), 150.8, 150.2 (d, J = 13.5 Hz), 149.4 (d, J = 13.5 Hz), 148.5 (d, J = 15.0 Hz), 147.7 (d, J = 15.0 Hz), 138.9 (d, J = 9.0 Hz), 132.2, 129.2, 128.0 (d, J = 9.0 Hz), 122.9, 106.6 (d, J = 21.0 Hz), 104.7 (d, J = 24.0 Hz), 74.4, 34.8, 21.3. 19 F NMR (565 MHz, CDCl 3 ) δ: -61.2 (d, J = 17.0 Hz), -62.0 (d, J = 22.6 Hz). HRMS (ESI) m / z Calcd for C 19 H 19 F 2 N 4 OS [M + H] + : 359.0773; Found: 359.0766.

[0147] Example 29

[0148]

[0149] The reaction steps and operations were the same as in Example 1, except that 4,5-diphenyl-1H-imidazole-2-thiol 55 (50.4 mg, 0.2 mmol) was added to the reaction system. The reaction was stopped, and the target product 56 (37.1 mg, 88% yield) was obtained as a pale yellow liquid after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0150] 6-Methyl-2,3-diphenyl-6-(phenyldiazenyl)-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-5-one (56): New compound, 37.1 mg, 88% yield. Pale yellow oil. 1 H NMR (CDCl 3 , 600 MHz) δ 7.72 - 7.70 (m, 2H), 7.49 - 7.45 (m, 6H), 7.43 - 7.41 (m, 4H), 7.21 - 7.17 (m, 3H), 3.89 (d, J = 13.8 Hz, 1H), 3.78 (d, J = 13.8 Hz, 1H), 1.72 (s, 3H). 13 C NMR (CDCl 3, 150 MHz) δ 167.3, 151.0, 143.7, 139.9, 132.6, 132.0, 131.5, 130.7, 129.3, 128.7, 128.7, 128.2, 127.9, 127.6, 127.5, 122.8, 74.6, 34.7, 21.4. HRMS(ESI) m / z Calcd for C 25 H 21 N 4 OS[M + H] + : 425.1431; Found: 425.1435.

[0151] Example 30

[0152]

[0153] The reaction steps and operations were the same as in Example 1, except that 57 deuterium water (42 μL, 2.0 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the white solid target product 58 (37.1 mg, yield 88%) was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0154] 3-Methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d (58): 1 HNMR(CDCl 3 , 600 MHz) δ 8.19 - 8.18 (m, 1H), 7.59 - 7.58 (m, 1H), 7.33 (td, J = 7.5, 1.3 Hz, 1H), 7.28 (td, J = 8.0, 1.3 Hz, 1H), 3.23 (d, J = 1.3 Hz, 2.04H), 1.52 (s, 3H).. 13 CNMR(CDCl 3 , 150 MHz) δ 169.9, 150.8, 143.1, 132.8, 125.6, 124.6, 118.6, 115.5, 39.1 (t, J = 21 Hz), 31.0, 15.3. 2 HNMR(92 MHz, CHCl 3 ) δ

[0155] 3.21. HRMS(APCI) m / z calcd for C 11 H 10 DN 2 OS[M + H] + : 220.0649; Found: 220.0644.

[0156] Example 31

[0157]

[0158] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 57 (42 μL, 2.0 mmol) of deuterium water and 59 (41.2 mg, 0.2 mmol) of 5-methyl-2-mercaptobenzimidazole were added to the reaction system. The reaction was stopped, and the target product 60 (34.8 mg, yield 75%) as a white solid was obtained after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0159] 3,7-dimethyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d and 3,8-dimethyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d (60): New compound, 34.8 mg, 75% yield. White solid, m.p.: 106.4 - 107.1 °C, Deuterium incorporation was determined by 1 1H NMR: 70%. 1 1H NMR (CDCl 3 , 600 MHz) δ

[0160] 8.03 (d, J = 8.2 Hz, 1H), 8.00 (s, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.36 (s, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.2 Hz, 1H), 3.22 - 3.21 (m, 4H), 3.19 - 3.17 (m, 0.6H), 2.45 (s, 3H), 2.43 (s, 3H), 1.51 (s, 6H). 13 13C NMR (CDCl 3, 150 MHz) δ 170.1 (d, J = 3.0 Hz), 169.8 (d, J = 3.0 Hz), 150.7, 149.9, 143.3, 141.0, 135.5, 134.8, 132.9, 130.7, 126.7, 125.7, 118.7, 118.0, 115.8, 115.0, 39.1 (t, 19.5 Hz), 31.1 (d, J = 7.5 Hz), 31.0 (d, J = 7.5 Hz), 21.8, 21.6, 15.4 (d, J = 4.5 Hz), 15.3 (d, J = 4.5 Hz). 2 1H NMR (92 MHz, CHCl 3 ) δ 3.17. HRMS (ESI) m / z Calcd for C 12 1H 12 1D 2 18O15N1S [M + H] + : 234.0806; Found: 234.0805.

[0161] Example 32

[0162]

[0163] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that 57 (42 μL, 2.0 mmol) of deuterium oxide and 61 (38.8 mg, 0.2 mmol) of 5-ethoxy-2-mercaptobenzimidazole were added to the reaction system. The reaction was stopped, and the target product 62 (29.1 mg, yield 55%) was obtained as a white solid after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0164] 7-ethoxy-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d and 8-ethoxy-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d (62): New compound, 29.1 mg, 55% yield. White solid, m.p.: 136.0 - 136.5 °C, Deuterium incorporation was determined by 1 1H NMR: 71%. 1 1H NMR (CDCl 3 , 600 MHz) δ

[0165] 8.03 (d, J = 8.8 Hz, 1H), 7.75 (d, J = 2.5 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.06 (d, J = 2.4 Hz, 1H), 6.92 - 6.90 (m, 1H), 6.87 - 6.85 (m, 1H), 4.08 - 4.04 (m, 4H),

[0166] 3.23 - 3.21 (m, 4H), 3.18 - 3.16 (m, 0.58H), 1.52 - 1.50 (m, 6H), 1.43 - 1.41 (m, 6H). 13 CNMR(CDCl 3 , 150 MHz) δ 170.2 (d, J = 1.5 Hz), 169.6 (d, J = 3.0 Hz), 157.4, 157.0, 151.2, 148.6, 144.2, 137.1, 133.5, 127.0, 118.9, 115.8, 114.3, 113.1, 102.9, 100.8, 64.3, 64.1, 39.7, 39.3, 38.9 (t, J = 19.5 Hz), 31.2 (t, J = 12 Hz), 31.0, 15.4 (d, J = 6.0 Hz), 15.3 (d, J = 6.0 Hz), 15.4 (d, J = 3.0 Hz). 2 HNMR(92 MHz, CHCl 3 ) δ 3.18. HRMS(ESI) m / z Calcd for C 13 H 14 DN 2 O 2 S[M + H] + : 264.0912; Found: 264.0910.

[0167] Example 33

[0168]

[0169] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 59 (42 μL, 2.0 mmol) of deuterium oxide and 63 (45.6 mg, 0.2 mmol) of 5-bromo-2-mercaptobenzimidazole were added to the reaction system. The reaction was stopped, and after post-treatment, the white solid target product 64 (42.4 mg, yield 71%) was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0170] 7-Bromo-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d and 8-Bromo-3-methyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d(64): New compound, 42.4 mg, 71% yield. White solid, m.p.: 161.3 - 161.7℃, D incorporation was determined by 1 HNMR: 71%. 1 HNMR(CDCl 3 , 600 MHz)δ

[0171] 8.38(s, 1H), 8.05(d, J=8.6 Hz, 1H), 7.71(d, J=1.8 Hz, 1H), 7.45 - 7.42(m, 2H), 7.40 - 7.38(m, 1H), 3.25 - 3.25(m, 4H), 3.23 - 3.20(m, 0.59H), 1.52(s, 6H). 13 CNMR(CDCl 3 , 150 MHz)δ169.8, 169.8, 152.4, 151.6, 144.3, 142.0, 133.6, 131.8, 128.8, 127.5, 125.5, 121.6, 119.6, 118.7, 118.7, 118.0, 116.6, 39.0(t, J=19.5 Hz), 31.1(d, J=9.0 Hz), 31.0(d, J=9.0 Hz), 17.1(d, J=12.0 Hz), 15.3(d, J=16.5 Hz). 2 HNMR(92 MHz, CHCl 3 )δ3.22. HRMS(ESI) m / z Calcd for C 11 H 9 DBrN 2 OS[M + H] + : 297.9755;Found: 297.9757.

[0172] Example 34

[0173]

[0174] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that 59 (42 μL, 2.0 mmol) of deuterium water and 65 (35.6 mg, 0.2 mmol) of 5,6-dimethyl-2-mercaptobenzimidazole were added to the reaction system. The reaction was stopped, and after post-treatment, the white solid target product 66 (38.5 mg, yield 78%) was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0175] 3,7,8-trimethyl-2,3-dihydro-4H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-4-one-3-d (66): New compound, 38.5 mg, 78% yield. White solid, m.p.: 177.1 - 178.0 °C, Deuterium incorporation was determined by 1 1H NMR: 68%. 1 1H NMR (CDCl 3 , 600 MHz) δ

[0176] 7.94 (s, 1H), 7.32 (m, 1H), 3.23 - 3.20 (m, 2H), 3.18 - 3.16 (m, 0.32H), 2.34 (s, 3H), 2.32 (s, 3H), 1.50 (s, 3H). 13 13C NMR (CDCl 3 , 150 MHz) δ 169.9, 149.5, 141.4, 134.3, 133.6, 131.1, 118.9, 115.9, 39.5, 39.1 (t, J = 21.0 Hz), 31.1 (d, J = 12.0 Hz), 20.4 (d, J = 13.5 Hz), 15.4 (d, J = 16.5 Hz). 2 1H NMR (92 MHz, CHCl 3 ) δ 3.18. HRMS (ESI) m / z Calcd for C 13 H 14 DN 2 OS [M + H] + : 248.0963; Found: 248.0964.

[0177] Example 35

[0178]

[0179] The reaction steps and operations were the same as those in Example 1, except that 59 (42 μL, 2.0 mmol) of deuterium water and 67 (50.4 mg, 0.2 mmol) of 4,5-diphenyl-1H-imidazole-2-thiol were added to the reaction system. The reaction was stopped, and the target product 68 (16.8 mg, yield 26%) as a white solid was obtained after post-treatment. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0180] 6-Methyl-2,3-diphenyl-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-5-one-6-d(68): New compound, 16.8 mg, 26% yield. White solid, m.p.: 187.8 - 188.7℃, Deuterium incorporation was determined by 1 1H NMR: 70%. 1 1H NMR(CDCl 3 , 600 MHz) δ

[0181] 7.42 - 7.39(m, 5H), 7.34 - 7.33(m, 2H), 7.20 - 7.18(m, 3H), 3.26 - 3.22(m, 1H), 3.18 - 3.16(m, 1H), 3.13 - 3.09(m, 0.3H), 1.41(d, J=7.0 Hz, 3H). 13 13C NMR(CDCl 3 , 150 MHz) δ 169.5, 144.7, 139.9, 132.6, 131.6, 130.6, 128.7, 128.6, 128.2, 127.9, 127.6, 127.5, 40.2, 39.8(t, J=19.5 Hz), 31.0(d, J=13.5 Hz), 15.5(d, J=16.5 Hz). 2 1H NMR(92 MHz, CHCl 3 ) δ 3.11. HRMS(ESI) m / z Calcd for C 19 18 16 D1 2 N2 + O2S [M + H]

[0182] The foregoing description of the disclosed embodiments enables those skilled in the art to practice or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An azo / deuterated imidazothiazinone compound, characterized in that: The chemical structural formula of the azo / deuterated imidazothiazinone compound is: in, R 1 is a phenylazo group, a naphthylazo group, a benzo[d][1,3]dioxinyl group, a benzo[d]thiazolyl group, a substituted phenylazo group or a deuterium atom; R 2 It is phenyl or substituted phenyl.

2. The azo / deuterated imidazothiazinone compound according to claim 1, characterized in that: R 1 In the above-mentioned, the substituent of the substituted phenylazo group is one of methyl, isopropyl, tert-butyl, trifluoromethyl, benzyl, ethoxy or halogen atom, and the number of the substituents is 1 or 2.

3. The azo / deuterated imidazothiazinone compound according to claim 1, characterized in that: R 2 In the above-mentioned substituted phenyl group, the substituent is one of a methyl group, an ethoxy group or a halogen atom, and the number of the substituents is 1 or 2.

4. An azo / deuterated imidazothiazinone compound according to claim 2 or 3, characterized in that: The halogen atom is selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

5. A method for synthesizing azo / deuterated imidazothiazinone compounds, characterized in that: The synthetic route is: At room temperature, aryl diazonium tetrafluoroborate 2 is used as a raw material, a reaction base is added, and acryloyl chloride 3 and 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives 4 are reacted to generate azo / deuterated imidazothiazinone compounds 1.

6. The method for synthesizing an azo / deuterated imidazothiazinone compound according to claim 5, characterized in that: It also includes replacing the aryldiazonium tetrafluoroborate 2 with deuterated water.

7. A method for synthesizing an azo / deuterated imidazothiazinone compound according to claim 4 or 5, characterized in that: The synthesis method is: At room temperature, aryl diazonium tetrafluoroborate or deuterated water, acryloyl chloride, 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives, and a base are added with a reaction solvent and reacted in an air atmosphere for 3-5 hours; after the reaction is completed, the mixture is separated and purified to obtain azo / deuterated imidazothiazinone compounds.

8. The method for synthesizing azo / deuterated imidazothiazinone compounds according to claim 7, characterized in that: The molar ratio of the aromatic diazonium tetrafluoroborate, acryloyl chloride, 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives, and the base is 0.1:0.2:0.2:0.1; The molar ratio of deuterated water, acryloyl chloride, 2-mercaptobenzimidazole and its derivatives or 2-mercaptoimidazole and its derivatives, and base is 2:0.2:0.2:0.

1.

9. The method for synthesizing azo / deuterated imidazothiazinone compounds according to claim 7, characterized in that: The reaction solvent is one of N,N-dimethylformamide, 1,2-dichloroethane, and acetonitrile; the base is one of pyridine, cesium carbonate, potassium tert-butoxide, and triethylamine; and the concentration of the base in the reaction solvent is 0.025 mmol / mL.

10. An application of an azo / deuterated imidazothiazinone compound in pharmaceutical synthesis, characterized in that: It is the azo / deuterated imidazothiazinone compound according to any one of claims 1 to 4, or the azo / deuterated imidazothiazinone compound prepared by the synthesis method according to any one of claims 5 to 9.

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