CN115785010A - Thio-1, 2, 3-triazole and efficient synthesis method thereof - Google Patents

Abstract

The invention discloses sulfo-1, 2, 3-triazole and an efficient synthesis method thereof, which are a method for efficiently and simply synthesizing a sulfur-containing 1,2, 3-triazole compound III-X by taking diphenyl phosphono sulfo-alkyne I and azide compound II as raw materials through different reactions under a protective atmosphere, and have the advantages of high yield, wide functional group tolerance range, simplicity and convenience in operation and the like.

Description

A class of thio-1,2,3-triazoles and its efficient synthesis method

technical field

The present invention relates to a kind of synthetic method of thio 1,2,3-triazole, particularly relate to diphenylphosphonothioalkyne as raw material, catalyze its cycloaddition reaction (CuAAC) with azide compound by copper , a method for synthesizing thio-1,2,3-triazoles belongs to the field of organic synthesis.

Background technique

Organosulfur compounds exist in many natural products and drug molecules, and are easily oxidized and can be used as anti-oxidative and anti-radiation drugs. The introduction of sulfur atoms into biologically active molecules can often increase their biological activity or pharmacodynamic activity. 1,2,3-Triazole compounds have a variety of biological activities, and are the skeleton structures of many biologically active compounds, drugs and pesticides. By introducing different substituents at different positions of the 1,2,3-triazole ring, molecules with different biological activities can be obtained. The introduction of sulfur substituents on the 1,2,3-triazole ring can obtain sulfur-containing 1,2,3-triazoles with specific biological activities.

Copper-catalyzed cycloaddition reaction of azides with sulfur alkynes (CuAAC) is a common method for constructing 1,2,3-triazole skeletons. There are two main methods for synthesizing sulfur-containing 1,2,3-triazole: the first method is to synthesize the 1,2,3-triazole skeleton first, and then synthesize sulfur-containing 1,2,3-triazole through SNAr reaction. Triazoles; The second method is the direct synthesis of sulfur-containing 1,2,3-triazoles by cycloaddition of sulfur-containing substrates with azide compounds. Although the above methods are effective in synthesizing sulfur-containing 1,2,3-triazoles, they also have the following disadvantages: for example, iodo-1,2,3-triazoles need to be converted into fluorinated 1,2,3-triazole, and then converted into the target sulfur-containing 1,2,3-triazole through SNAr reaction); need to use noble metals such as Ir, Ru catalyst; only aryl sulfur 1,2,3- Triazoles, the scope of substrates needs to be further expanded. Therefore, the development of a new efficient synthesis method of sulfur-containing 1,2,3-triazole has great theoretical research significance and practical application value.

Contents of the invention

The object of the present invention is to provide a kind of efficient and convenient synthesis of sulfur-containing 1,2,3-tri-alkyne I and azide compound II under different conditions by using diphenylphosphonothioalkyne I and azide compound II as raw materials. The method of azole compound III-X. This method has the advantages of high yield, wide tolerance range of functional groups and simple operation.

In order to achieve the above-mentioned technical purpose, the present invention provides under the action of copper catalyst cat.1 and alkali reagent, THF, ethanol, propanol, n-propanol, iso Propanol, butanol, isobutanol, tert-butanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, 1,4-dioxane, DMF, DMSO or toluene solution system (or add organic amine) , at a specific temperature T1, react for a certain time t1, after the reaction is completed, extract with a common organic solvent, dry, filter, and pass column chromatography to obtain the product 4-mercapto-1,2,3-triazole III. Under the action of m-chloroperoxybenzoic acid (mCPBA), THF, dichloromethane, chloroform, diethyl ether, acetone, ethanol, ethylene glycol diethyl ether of 4-mercapto-1,2,3-triazole III , diethylene glycol diethyl ether, 1,4-dioxane, DMF, DMSO or toluene solution system, at a specific temperature T2, react for a certain time t2, after the reaction is complete, extract with a common organic solvent, dry, filter, The product 4-sulfone-1,2,3-triazole IV can be obtained by column chromatography. Under the action of copper catalyst cat.2 and sodium ascorbate, THF, ethanol, propanol, n-propanol, isopropanol, butanol, isobutanol, In tert-butanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, 1,4-dioxane, DMF, DMSO, NMP or toluene solution system, at a specific temperature T3, react for a certain time t3, the reaction is complete, and use a common Organic solvent extraction, drying, filtration, and column chromatography can give the products phosphono- and mercapto-substituted 1,2,3-triazoles V and VI. Under the action of mCPBA, THF, dichloromethane, chloroform, ether, acetone, ethanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, 1,4- In dioxane, DMF, DMSO or toluene solution system, at a specific temperature T4, react for a certain time t4, after the reaction is completed, extract with a common organic solvent, dry, filter, and spin the filtrate to obtain a crude product, where the crude product and Azide II solution in THF, ethanol, propanol, n-propanol, isopropanol, butanol, isobutanol, tert-butanol, ethylene glycol diethyl ether, diethylene glycol diethyl ether, DMF, DMSO or toluene In the system, at a specific temperature T5, react for a certain time t5, after the reaction is completed, extract with a common organic solvent, dry, filter, and pass column chromatography to obtain the product phosphono and mercapto substituted 1,2,3-triazole VII and VIII. THF, ethanol, propanol, n-propanol, isopropanol, butanol, isobutanol, tert-butanol, ethyl Glycol diethyl ether, diethylene glycol diethyl ether, DMF, DMSO, toluene or xylene solution system, at a specific temperature T6, react for a certain time t6, after the reaction is completed, extract with a common organic solvent, dry, filter, and pass through the column The product phosphine and mercapto-substituted 1,2,3-triazole IX can be obtained by chromatography. THF, dichloromethane, chloroform, diethyl ether, 1,4-dioxane, ethylene glycol diethyl ether, diethylene glycol substituted with phosphono and mercapto substituted 1,2,3-triazole V and MeMgBr In the diethyl ether or toluene solution system, at a specific temperature T7, react for a certain time t7, the reaction is completed, add aromatic aldehyde to the reaction solution, and at a specific temperature T8, react for a certain time t8, after the reaction is completed, extract with a common organic solvent , dry, filter, and pass column chromatography to obtain the product 1,2,3-triazole X substituted by hydroxyl and mercapto groups. Under the action of alkaline reagents, THF, dichloromethane, chloroform, diethyl ether, 1,4-dioxane, ethylene glycol diethyl ether, In diethylene glycol diethyl ether or toluene solution system, at a specific temperature T9, react for a certain time t9, after the reaction is completed, extract with a common organic solvent, dry, filter, and get the product 5-mercapto-1 by column chromatography, 2,3-Triazole Ⅺ. The product bis-4-mercapto-1,2,3-triazoles Ⅻ-1, Ⅻ-2, Ⅻ-3, Ⅻ-4 can be obtained through the steps of preparation Ⅲ.

Wherein said R ¹ , R ² , R ³ are functional groups such as aryl or alkyl.

In the above-mentioned synthetic method, the alkynyl bromide reagent is the following compound:

In the above synthesis method, phenylphosphonothioalkyne I is one of the following compounds:

In the above synthesis method, the azide compound II is one of the following compounds:

In the above synthesis method, the copper catalyst cat.1 is one of the following compounds: one of copper iodide (CuI) and tetraacetonitrile copper hexafluorophosphonate (Cu(MeCN) ₄ PF ₆ ).

In the above synthesis method, the alkaline reagent is one of the following compounds: potassium tert-butoxide (tBuOK).

In the above synthesis method, the organic amine is N,N'-dimethylethylenediamine (DMEDA).

In the above synthesis method, the copper catalyst cat.2 is one of the following copper catalysts: one of CuI, Cu(MeCN) ₄ BF ₄ , CuI/CuSO ₄ -5H ₂ O.

In the above synthetic method, the aromatic aldehyde is one of the following compounds:

In the above synthesis method, the reaction temperature T1 is 50-140°C, T2 is -20-60°C, T3 is 80-200°C, T4 is -20-60°C, T5 is 50-180°C, T6 is 60- 150°C, T7 is -20-60°C, T8 is -20-80°C, T9 is -20-60°C.

In the above synthesis method, the reaction time t1 is 2-24h, t2 is 0.5-24h, t3 is 5-48h, t4 is 0.5-24h, t5 is 5-48h, t6 is 2-24h, t7 is 0.5-24h , t8 is 1-48h, t9 is 0.5-24h.

In the above synthesis method, the commonly used organic solvent for extraction after the reaction is one of CH ₂ Cl ₂ , chloroform, toluene, diethyl ether, petroleum ether, n-hexane, and ethyl acetate.

The synthesis method provided by the present invention is to use diphenylphosphonothioalkyne as a raw material, and catalyze its cycloaddition reaction (CuAAC) with an azide compound through copper to synthesize thio1,2,3-triazole , opened up a new synthesis route for thio-1,2,3-triazoles, and its advantages are: (1) no need to separate intermediates; (2) under mild reaction conditions, high yield, wide range of functional group tolerance; (3) Easy to operate.

Description of drawings

Fig. 1 shows the cycloaddition reaction (CuAAC) of diphenylphosphonothioalkyne and azide compound provided by the present invention to synthesize thio-1,2,3-triazole route diagram.

Detailed ways

In order to make the above features, advantages and objectives of the present invention more comprehensible, specific implementations of the present invention will be described in detail below in conjunction with the accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, the present invention can be implemented in many other ways different from those described here, and those skilled in the art can make similar improvements without departing from the connotation of the present invention, so the present invention is not limited by the specific implementation disclosed below.

Example 1

The structural formula of the target product is as follows:

At room temperature, add 0.5mmol Ⅰ-1, 0.6mmol azide Ⅱ-1, 0.05mmol CuI, 0.75mmol t-BuOK and 2mL nPrOH into a 10mL reaction tube, react at 110°C for 12h, cool to room temperature, add saturated chlorine Ammonium chloride aqueous solution and 10mL ethyl acetate were extracted and separated, and the product 1-benzyl-4-(p-methylphenylmercapto)-1H-1,2,3-triazole III-1 was obtained by column chromatography. The rate is 82%.

Ⅲ-1 is white powder. Melting point (MP): 98-100℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.50 (s, 1H), 7.37 (br, 3H), 7.26–7.22 (m, 4H), 7.06 (d, J＝ 8.0Hz,2H),5.52(s,2H),2.29(s,3H) ^.13 CNMR(101MHz,CDCl ₃ )δ139.76,136.96,134.12,131.53,129.81,129.68,129.15,128.88,128.09,126.74,54.43, 20.94. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₁₅ N ₃ S 281.0987; Found, 281.0985.

Example 2

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-2 and II-1 as raw materials.

III-2 is a white solid with a yield of 84%.

Melting point(MP):157-159℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.57(s,1H),7.38–7.34(m,5H),7.29–7.27(m,2H),7.14(d , J＝8.4Hz, 2H), 5.55(s, 2H). ¹³ C NMR (101MHz, CDCl ₃ ) δ137.96, 134.73, 133.90, 132.02, 130.21, 129.23, 129.01, 128.15, 127.49, 120.58, 54.56. HRMS-ESI (m/z)[M+H] ⁺ Calcd for C ₁₅ H ₁₂ BrN ₃ S 344.9935; Found, 344.9934.

Example 3

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-3 and II-1 as raw materials.

III-3 is a white solid with a yield of 78%.

Melting point(MP):112-114℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.56(s,1H),7.40-7.38(m,3H),7.29–7.27(m,2H),7.20(br ,4H),5.55(s,2H). ¹³ C NMR(101MHz,CDCl ₃ )δ138.17,133.98,133.92,132.70,130.06,129.23,129.12,129.01,128.15,127.40,54.55.HRMS-ESI(m/z) [M+H] ⁺ Calcd for C ₁₅ H ₁₂ ClN ₃ S 301.0440; Found, 301.0441.

Example 4

The structural formula of the target product is as follows:

The procedure is the same as in Example 1, using I-9 and II-1 as raw materials.

III-4 is a white solid with a yield of 85%.

Melting point(MP):117-119℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.52(s,1H),7.41–7.36(m,3H),7.28–7.23(m,6H),5.53(s, 2H),1.27(s,9H) ^.13C NMR(101MHz,CDCl ₃ )δ149.98,139.24,134.08,131.61,129.07,129.04,128.78,128.03,127.02,126.05,77.32,75.00,76.67,31.32,53.7 .HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₉ H ₂₁ N ₃ S 323.1456; Found, 323.1454.

Example 5

The structural formula of the target product is as follows:

The procedure is the same as in Example 1, using I-5 and II-1 as raw materials.

III-5 is a white solid with a yield of 82%.

Melting point (MP): 84-86℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.43 (s, 1H), 7.37-7.35 (m, 5H), 7.24 (d, J＝7.4Hz, 2H), 6.81 (d, J=8.8Hz, 2H), 5.49(s, 2H), 3.77(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ159.32, 141.14, 134.13, 132.72, 129.15, 128.87, 128.09, 125.85, 125.04, 114.73, 55.32, 54.41. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₁₅ N ₃ OS 297.0936; Found, 297.0935.

Example 6

The structural formula of the target product is as follows:

The procedure is the same as in Example 1, using I-6 and II-1 as raw materials.

III-6 is a white solid with a yield of 81%.

Melting point(MP):140-142℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.77-7.67(m,4H),7.58(s,1H),7.47–7.38(m,6H),7.29–7.27 (m,2H),5.59(s,2H). ¹³ C NMR(101MHz,CDCl ₃ )δ138.74,134.05,133.55,132.73,131.98,129.51,128.88,128.69,128.06,127.63,127.42,127.312,126.2 126.58,125.98,54.46. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₉ H ₁₅ N ₃ S317.0987; Found, 317.0988.

Example 7

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-13 and II-1 as raw materials.

III-7 is a white solid with a yield of 77%.

Melting point (MP): 63-65℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.38(d, J=6.8Hz, 4H), 7.26(t, J=4.3Hz, 2H), 5.51(s, 2H), 2.90(t, J=7.4Hz, 2H), 1.59(q, J=7.5Hz, 2H), 1.34-1.38(m, 2H), 1.24(br, 16H), 0.88(t, J=6.7 Hz,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ140.91,134.37,129.15,128.84,128.07,124.74,54.34,34.95,31.90,29.71,29.62,29.56,29.48,29.33,29.13,228.57 HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₁ H ₃₃ N ₃ S 359.2395; Found, 359.2396.

Example 8

The structural formula of the target product is as follows:

The procedure is the same as in Example 1, using I-10 and II-1 as raw materials.

III-8 is a colorless liquid with a yield of 74%.

¹ H NMR (400MHz, CDCl ₃ ) δ7.44(s, 1H), 7.39-7.37(m, 3H), 7.26(d, J=8.0Hz, 2H), 5.52(s, 2H), 3.12(q, J＝8.0Hz, 1H), 1.66-1.59(m, 1H), 1.54-1.47(m, 1H), 1.24(d, J＝6.8Hz, 3H), 0.99(t, J＝8.0Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ139.28, 134.33, 129.13, 128.81, 128.00, 126.67, 54.27, 45.68, 29.57, 20.77, 11.40. HRMS-ESI (m/z) [M+H] ⁺ CalcdforC ₁₃ H ₁₇ N ₃ S 247.1143; Found, 247.1142.

Example 9

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-1 and II-2 as raw materials.

III-9 is a white solid with a yield of 60%.

Melting point(MP):128-132℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.52(s,1H),7.49(d,J=4.0Hz,2H),7.24(d,J=8.0Hz, 2H), 7.13(d, J=8.0Hz, 2H), 7.07(d, J=8.0Hz, 2H), 5.46(s, 2H), 2.29(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ140.33,137.19,133.16,132.38,131.29,129.96,129.88,129.69,126.51,123.13,53.74,20.99. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₁₄ BrN Found ₃ S359.0092; ,359.0093.

Example 10

The structural formula of the target product is as follows:

The procedure is the same as in Example 1, using I-1 and II-3 as raw materials.

III-10 is a white solid with a yield of 60%.

Melting point(MP):87-89℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.39(s,1H),7.30-7.26(m,1H),7.23-7.19(m,4H),7.15(d , J＝8Hz, 1H), 7.05(d, J＝8Hz, 2H), 5.53(s, 2H), 2.28(s, 3H), 2.26(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ139 .32,136.87,136.84,131.97,131.69,131.06,129.77,129.45,129.26,126.72,126.67,51.99,20.47,18.39.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₁₇ N ₃ S 295.1143; Found, 295.1142.

Example 11

The structural formula of the target product is as follows:

The procedure is the same as in Example 1, using I-1 and II-4 as raw materials.

III-11 is a white solid with a yield of 88%.

Melting point(MP):102-104℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.47(s,1H),7.22–7.15(m,6H),7.05(d,J＝7.8Hz,2H), 5.47(s,2H),2.35(s,3H),2.29(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ139.43,138.78,136.83,131.57,131.03,129.75,129.51,128.10,126.73,77.32, 77.00,76.68,54.18,21.08,20.91. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₁₇ N ₃ S 295.1143; Found, 295.1144.

Example 12

The structural formula of the target product is as follows:

The procedure is the same as in Example 1, using I-1 and II-5 as raw materials.

III-12 is a white solid with a yield of 67%.

Melting point(MP):102-105℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.46(s,1H),7.23-7.20(m,4H),7.05(d,J＝8.0Hz,2H), 6.89(d, J=8.0Hz, 2H), 5.45(s, 2H), 3.81(s, 3H), 2.29(s, 3H). ¹³ C NMR(101MHz, CDCl ₃ ) δ160.02, 139.55, 136.92, 131.63, 129.80,129.74,129.62,126.60,126.02,114.52,55.33,54.03,20.98. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₁₇ N ₃ OS311.1092; Found, 311.1090.

Example 13

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-1 and II-6 as raw materials.

III-13 is a white solid with a yield of 83%.

Melting point (MP): 137-139℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.64 (d, J＝8.0Hz, 2H),

7.52(s,1H),7.37(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H),7.08(d,J=4Hz,2H),5.58(s,2H),2.30 (s,3H) ^.13 C NMR(101MHz,CDCl ₃ )δ140.41,138.12(q,J=1.0Hz),137.23,131.11,131.06(q,J=32.8Hz),129.92,129.88,128.21,126.71,126.10 (q, J=4.0Hz), 123.68(q, J=273.7Hz), 53.65, 20.94. ¹⁹ F NMR (376MHz, CDCl ₃ ) δ62.75.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₁₄ F ₃ N ₃ S 349.0861; Found, 349.0860.

Example 14

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-1 and II-6 as raw materials.

III-14 is a white solid with a yield of 70%.

Melting point (MP): 102-107℃; ¹ HNMR (400MHz, CDCl ₃ ) δ7.49(s, 1H), 7.36-7.35(m, 7H), 7.21(d, J＝8.0Hz, 2H), 7.11– 7.05(m,6H),2.28(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ

138.87,137.75,136.80,131.79,129.80,129.31,128.98,128.69,128.01,127.17,68.55,20.93. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₂ H ₁₉ N ₃ S 357.1300; ,357.1303.

Example 15

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-1 and II-6 as raw materials.

III-15 is a white solid with a yield of 75%.

Melting point(MP):69-71℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.55(s,1H),7.39-7.34(m,5H),7.28(d,J＝7.5Hz,2H), 7.12(d, J=8.5Hz, 2H), 5.82(q, J=8.0Hz, 1H), 2.00(d, J=8.0Hz, 3H). ¹³ C NMR(101MHz, CDCl ₃ ) δ139.21, 137.37, 134.90 ,132.02,130.10,129.16,128.83,126.53,120.50,60.85,21.20.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₁₄ BrN ₃ S359.0092; Found,359.0091.

Example 15

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-1 and II-6 as raw materials.

III-16 is a white solid with a yield of 76%.

Melting point(MP):73-75℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.91-7.89(m,3H),7.53–7.41(m,4H),7.36(s,1H),7.13(d , J＝8.0Hz, 2H), 7.00(d, J＝8.0Hz, 2H), 5.96(s, 2H), 2.25(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ139.26, 136.72, 133.87, 131.61,131.00,130.14,129.70,129.30,128.92,127.94,127.28,126.96,126.38,125.26,122.67,52.59,20.87. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₀₃ H _{N 17} S 331.1143; Found, 331.1142.

Example 16

The structural formula of the target product is as follows:

The steps are the same as in Example 1, using I-1 and II-6 as raw materials.

III-17 is a white solid with a yield of 74%.

Melting point(MP):177-182℃; ¹ H NMR(400MHz, CDCl ₃ )δ8.59(s,1H),8.27(d,J＝8.0Hz,2H),8.08(d,J＝8.0Hz, 2H), 7.61(t, J=8.0Hz, 2H), 7.53(t, J=8.0Hz, 2H), 7.20(s, 1H), 7.09(d, J=8.0Hz, 2H), 6.97(d, J＝8.0Hz, 2H), 6.55(s, 2H), 2.24(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ138.83, 136.69, 131.68, 131.44, 130.78, 130.09, 129.69, 129.54, 129.23, 127.80 ,126.79,125.45,123.23,122.79,46.81,20.92. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₄ H ₁₉ N ₃ S 381.1300; Found, 381.1303.

Example 17

The structural formula of the target product is as follows:

At room temperature, add 0.5 mmol Ⅰ-1, 0.6 mmol azide Ⅱ-26, 0.05 mmol CuI, 0.75 mmol t-BuOK, 0.05 mmol DMEDA and 2 mL nPrOH into a 10 mL reaction tube, react at room temperature for 15 h, cool to room temperature, Add saturated ammonium chloride aqueous solution and 10mL ethyl acetate for extraction and separation, and obtain the product 4-(p-methylphenylmercapto)-1-(4-trifluoromethylphenyl)1H-1,2 by column chromatography. 3-Triazole, 83% yield.

4-(p-methylphenylmercapto)-1-(4-trifluoromethylphenyl)1H-1,2,3-triazole III-18 is a white powder.

Melting point(MP):148-150℃; ¹ H NMR(400MHz, CDCl ₃ )δ8.03(s,1H),7.87(d,J＝8.0Hz,2H),7.80(d,J＝8.0Hz, 2H), 7.36(d, J=8.0Hz, 2H), 7.12(d, J=8.0Hz, 2H), 2.32(s, 3H). ¹³ C NMR(101MHz, CDCl ₃ )δ141.87, 139.03, 137.72, 130.92 (q, J=33.3Hz),130.60,130.50,130.05,127.12(q,J=4.0Hz),124.15,123.44(q,J=273.7Hz), ^{120.33,21.00.19} FNMR(376MHz,CDCl ₃ )δ62 .66. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₁₂ F ₃ N ₃ S 335.0704; Found, 335.0701.

Example 18

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-11 as raw materials.

III-19 is a yellow liquid with a yield of 79%.

Melting point (MP): 149-150℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.57(s, 1H), 7.24(d, J＝8.0Hz, 2H), 7.07(d, J＝8.0Hz, 2H), 4.34(t, J=7.2Hz, 2H), 2.30(s, 3H), 1.89(q, J=7.2Hz, 2H), 1.31(br, 6H), 0.91-0.85(m, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ139.18, 136.90, 131.85, 129.83, 129.59, 126.72, 50.67, 31.06, 30.10, 26.07, 22.36, 20.97, 13.87. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₁₅ H ₂₁ N ₃ S 275.1456; Found, 275.1455.

Example 19

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-2 and II-26 as raw materials.

III-20 is a white solid with a yield of 82%.

Melting point (MP): 123-124°C; ¹ H NMR (400MHz, CDCl ₃ ) δ1H NMR 8.15(s, 1H), 7.90(d, J＝8.0Hz, 2H), 7.82(d, J＝8.0Hz, 2H), 7.41(d, J=8.0Hz, 2H), 7.27(d, J=8.0Hz, 2H). ¹³ C NMR (101MHz, CDCl ₃ ) δ140.00, 138.93, 137.74, 132.31, 131.20(q, J= 34.3Hz), 131.12, 127.24(q, J=4.0Hz), 125.01, 123.40(q, J=275.7Hz), 121.37, 120.42. ¹⁹ F NMR(376MHz, CDCl ₃ ) δ62.69.HRMS-ESI(m /z) [M+H] ⁺ Calcd for C ₁₅ H ₉ BrF ₃ N ₃ S 398.9653; Found, 398.9651. Example 20

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-3 and II-26 as raw materials.

III-21 is a white solid with a yield of 80%.

Melting point (MP): 119-122℃; ¹ H NMR (400MHz, CDCl ₃ ) δ8.14(s, 1H), 7.90(d, J=8.0Hz, 2H), 7.82(d, J=8.0Hz, 2H ),7.34(d,J＝8.0Hz,2H),7.26(d,J＝8.0Hz,2H). ¹³ CNMR(101MHz,CDCl ₃ )δ140.22,138.94,133.48,133.00,131.20(q,J＝32.3Hz ), 130.99, 129.39, 127.24 (q, J=4.0Hz), 124.92, 123.42 (q, J=273.7Hz), 120.42. ¹⁹ F NMR (376MHz, CDCl ₃ ) δ62.69.HRMS-ESI (m/z )[M+H] ⁺ Calcd for C ₁₅ H ₉ ClF ₃ N ₃ S 355.0158; Found, 355.0157.

Example 21

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-6 and II-26 as raw materials.

III-22 is a white solid with a yield of 76%.

Melting point(MP):154-156℃; ¹ H NMR(400MHz,CDCl ₃ )δ8.12(s,1H),7.89(br,3H),7.82-7.74(m,5H),7.49-7.47(m ,3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ140.95, 138.99, 133.63, 132.30, 131.62, 131.04 (q, J＝33.3Hz), 129.04, 128.63, 127.73, 127.62 (q, J＝265.6Hz), 127.39 ,127.31,127.17(q,J=4.0Hz),126.79,126.38,124.79,120.36. ¹⁹ F NMR(376MHz,CDCl ₃ )δ62.65.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₉ H ₁₂ F ₃ N ₃ S 371.0704; Found, 371.0703.

Example 22

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-27 as raw materials.

III-23 is a white solid with a yield of 91%.

Melting point (MP): 109-110℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.96(s, 1H), 7.58(d, J＝8.0Hz, 2H), 7.31(t, J＝8.0Hz, 4H),7.09(d,J＝8.0Hz,2H),2.41(s,3H),2.30(s,3H) ^.13 CNMR(101MHz,CDCl ₃ )δ140.38,139.15,137.23,134.38,131.23,130.24,130.08 ,129.90,124.72,120.29,77.32,77.00,76.68,21.05,20.97. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₁₅ N ₃ S281.0987; Found, 281.0985.

Example 23

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-28 as raw materials.

III-24 is a white solid with a yield of 88%.

Melting point(MP):101-103℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.92(s,1H),7.58(d,J＝8.5Hz,2H),7.32(d,J＝7.8Hz, 2H), 7.09(d, J=7.8Hz, 2H), 6.99(d, J=8.6Hz, 2H), 4.07(q, J=7.0Hz, 2H), 2.30(s, 3H), 1.44(t, J＝7.0Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ159.36, 140.22, 136.27, 131.97, 130.04, 129.94, 129.90, 124.88, 122.04, 115.26, 77.32, 77.00, 75.68, 6698, 14.HRMS -ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₁₇ N ₃ OS 311.1092; Found, 311.1094.

Example 24

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-9 and II-39 as raw materials.

III-25 is a white solid with a yield of 68%.

Melting point(MP):123-125℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.99(s,1H),7.85(d,J＝8.8Hz,2H),7.48(d,J＝8.8Hz, 2H), 7.36(d, J＝8.6Hz, 2H), 7.31(d, J＝8.6Hz, 2H), 1.28(s, 9H). ¹³ C NMR (101MHz, CDCl ₃ ) δ150.71, 141.10, 138.92, 136.33 ,130.91,130.00,126.32,124.38,121.91,93.92,34.53,31.21.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₈ H ₁₈ IN ₃ S435.0266; Found,435.0265.

Example 25

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-9 and II-40 as raw materials.

III-26 is a white solid with a yield of 65%.

Melting point (MP): 107-109℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.99(s, 1H), 7.67(d, J＝8.8Hz, 2H), 7.49(d, J＝8.8Hz, 2H), 7.37(d, J＝8.6Hz, 2H), 7.31(d, J＝8.5Hz, 2H), 1.29(s, 9H). ¹³ C NMR (101MHz, CDCl ₃ ) δ150.70, 141.06, 135.19, 134.84 ,130.94,130.00,126.32,124.56,121.60,34.53,31.20. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₈ H ₁₈ ClN ₃ S 343.0910; Found, 343.0907.

Example 26

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-9 and II-29 as raw materials.

III-27 is a white solid with a yield of 72%.

Melting point (MP): 100-102°C; ¹ H NMR (400MHz, CDCl ₃ ) δ8.26(s, 1H), 8.10(s, 1H), 8.00(t, J=7.5Hz, 2H), 7.65( t, J=7.4Hz, 1H), 7.38(d, J=8.0Hz, 2H), 7.32(d, J=8.0Hz, 2H), 2.66(s, 3H), 1.29(s, 9H). ¹³ C NMR(101MHz, CDCl ₃ )δ196.51, 150.75, 141.34, 138.53, 137.12, 130.83, 130.29, 130.10, 128.64, 126.34, 124.65, 124.59, 119.60, 34.52, 31.19+, 26.70.MS H] ⁺ Calcd for C ₂₀ H ₂₁ N ₃ OS 351.1405; Found, 351.1404.

Example 27

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-30 as raw materials.

III-28 is a white solid with a yield of 80%.

Melting point (MP): 60-62°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.97(s, 1H), 7.31(t, J=4.0Hz, 4H), 7.11(s, 1H), 7.08( d, J＝7.8Hz, 2H), 2.39(s, 6H), 2.31(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ140.36, 139.77, 137.22, 136.61, 131.35, 130.60, 130.07, 129.92, 124.87 ,118.24,21.26,21.00. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₁₇ N ₃ S 295.1143; Found, 295.1140.

Example 28

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-31 as raw materials.

III-29 is a white solid with a yield of 78%.

Melting point(MP):82-84℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.96(s,1H),7.32(d,J＝8.0Hz,3H),7.16-7.06(m,3H), 6.94(d, J=8.6Hz, 1H), 3.94(d, J=6.5Hz, 6H), 2.31(s, 3H). ¹³ CNMR(101MHz, CDCl ₃ )δ149.86, 149.64, 140.35, 137.26, 131.32, 130.30 ,130.08,129.92,124.98,112.42,111.23,104.93,56.25,56.19,20.98.HRMS-ESI(m/z)[M+H] ⁺ Calcd for _{C 17} H ₁₇ N ₃ O ₂ S327.1041; Found,327.1040.

Example 29

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-32 as raw materials.

III-30 is a white solid, the yield is 62%.

Melting point (MP): 156-161°C; ¹ H NMR (400MHz, CDCl ₃ ) δ8.05(s, 1H), 7.92(s, 1H), 7.88(d, J=8.2Hz, 1H), 7.83( d,J=7.5Hz,1H),7.69(d,J=8.3Hz,1H),7.59(d,J=7.4Hz,1H),7.43(t,J=7.5Hz,1H),7.36(dd, J=11.4,7.5Hz,3H),7.12(d,J=7.8Hz,2H),3.99(s,2H),2.32(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ144.87,143.51,142.69 ,140.68,140.29,137.38,135.33,131.28,130.25,130.00,127.60,127.17,125.22,124.86,120.72,120.34,119.42,117.56,37 ⁺ 07,21.05.HRMS-ESI(m for C ₂₂ H ₁₇ N ₃ S355.1143; Found, 355.1142.

Example 30

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-33 as raw materials.

III-31 is a yellow liquid with a yield of 73%.

¹ H NMR (400MHz, CDCl ₃ ) δ8.03-8.01 (m, 1H), 7.96-7.94 (m, 2H), 7.60-7.56 (m, 5H), 7.40 (d, J=8.0Hz, 2H), 2.32(s,3H) ^.13C NMR(101MHz,CDCl ₃ )δ140.01,137.38,134.10,133.26,131.11,130.60,130.28,129.99,129.02,128.29,127.99,127.11,124.901,1223.5 ESI(m/z)[M+H] ⁺ Calcd for C ₁₉ H ₁₅ N ₃ S 317.0987; Found, 317.0986.

Example 31

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-34 as raw materials.

Ⅲ-32 is a green liquid with a yield of 70%.

¹ H NMR (400MHz, CDCl ₃ ) δ8.78(d, J=8.0Hz, 1H), 8.74(d, J=8.0Hz, 1H), 7.99(s, 1H), 7.93(d, J=7.9Hz ,1H),7.88(s,1H),7.80–7.74(m,2H),7.68(d,J=8.0Hz,1H),7.62(d,J=8.0Hz,1H),7.56(d,J= 8.0Hz, 1H), 7.42(d, J＝12.0Hz, 2H), 7.15(d, J＝8.0Hz, 2H), 2.33(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ140.08, 137.45, 132.06, 131.13, 130.75, 130.34, 130.17, 130.04, 129.30, 129.24, 128.46, 127.94, 127.82, 127.65, 127.24, 124.92, 123.14, 123.00, 122.85 HR/ ^21.06 Calcd for C ₂₃ H ₁₇ N ₃ S 367.1143; Found, 367.1141.

Example 32

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-35 as raw materials.

III-33 is a white solid with a yield of 61%.

¹ H NMR (400MHz, CDCl ₃ ) δ8.29(d, J=7.6Hz, 1H), 8.25(d, J=7.9Hz, 2H), 8.18(t, J=9.4Hz, 2H), 8.13(s ,1H),8.10(d,J=8.2Hz,1H),8.07(s,1H),8.03(d,J=8.1Hz,1H),7.83(d,J=9.3Hz,1H),7.45(d , J＝7.9Hz, 2H), 7.16(d, J＝7.9Hz, 2H), 2.34(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ140.21, 137.44, 132.39, 131.23, 131.11, 130.61, 130.37 , ^{130.05,129.98,129.88,129.49,129.09,126.94,126.83,126.52,126.18,126.06,125.02,124.69,124.11,123.26,120.84,21.06} . ₂₅ H ₁₇ N ₃ S 391.1143; Found, 391.1145.

Example 33

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-37 as raw materials.

III-34 is a white solid with a yield of 93%.

Melting point(MP):128-129℃; ¹ H NMR(400MHz,CDCl ₃ )δ8.03(s,1H),7.80–7.73(m,4H),7.62(d,J＝8.0Hz,2H), 7.48(t, J=8.0Hz, 2H), 7.42-7.34(m, 3H), 7.12(d, J=8.0Hz, 2H), 2.32(s, 3H). ¹³ C NMR(101MHz, CDCl ₃ )δ141 .91,140.75,139.40,137.33,135.68,131.07,129.94,128.94,128.30,127.97,127.00,124.54,120.62,20.98.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₁ H ₁₇ N ₃ 343.1143; Found, 343.1142.

Example 34

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-12 and II-37 as raw materials.

III-35 is a white solid with a yield of 62%.

Melting point(MP):95-97℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.96(s,1H),7.80(d,J＝8.0Hz,2H),7.74(d,J＝8.0Hz, 2H), 7.62(d, J=8.0Hz, 2H), 7.48(t, J=8.0Hz, 2H), 7.40(t, J=8.0Hz, 1H), 3.01(d, J=8.0Hz, 2H) , 1.70(p, J=8.0Hz, 2H), 1.43(t, J=8.0Hz, 2H), 1.27(br, 8H), 0.87(t, J=8.0Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ )δ141.82, 141.50, 139.51, 135.85, 128.97, 128.34, 127.96, 127.04, 122.76, 120.61, 34.94, 31.75, 29.77, 29.14, 29.07, 28.58, 22.60, 14.ES-I H] ⁺ Calcd for C ₂₂ H ₂₇ N ₃ S 365.1926; Found, 365.1925.

Example 35

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-13 and II-37 as raw materials.

III-36 is a white solid with a yield of 72%.

Melting point(MP):121-123℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.96(s,1H),7.80(d,J＝8.0Hz,2H),7.74(d,J＝8.0Hz, 2H), 7.62(d, J=8.0Hz, 2H), 7.48(t, J=8.0Hz, 2H), 7.40(t, J=8.0Hz, 1H), 3.01(t, J=8.0Hz, 2H) ,1.73-1.65(m,2H),1.43(t,J=8.0Hz,2H),1.25(br,16H),0.88(t,J=8.0Hz,3H). ¹³ C NMR(101MHz,CDCl ₃ ) δ141.87,141.53,139.55,135.88,128.98,128.37,127.98,127.06,122.75,120.65,34.96,31.89,29.80,29.63,29.61,29.57,29.51,29.32,29.13,28.59,22.66,14.09.HRMS-ESI(m/ z) [M+H] ⁺ Calcd for C ₂₆ H ₃₅ N ₃ S 421.2552; Found, 421.2551.

Example 36

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-10 and II-37 as raw materials.

III-37 is a white solid with a yield of 74%.

Melting point(MP):85-87℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.95(s,1H),7.80-7.78(m,2H),7.75-7.73(m,2H),7.62(d ,J=8.0Hz,2H),7.48(t,J=8.0Hz,2H),7.42-7.38(m,1H),3.10-3.05(m,1H),2.91-2.85(m,1H),1.72- 1.68(m,1H),1.58-1.54(m,1H),1.30-1.26(m,1H),1.05(d,J＝8.0Hz,3H),0.91(t,J＝8.0Hz,3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ142.01, 141.78, 139.50, 135.84, 128.95, 128.31, 127.94, 127.02, 122.36, 120.58, 41.94, 34.85, 28.46, 18.57, 11.17. HRMS-ESI (m/z) [ ] ⁺ Calcd for C ₁₉ H ₂₁ N ₃ S 323.1456; Found, 323.1455.

Example 37

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-11 and II-37 as raw materials.

III-38 is a white solid with a yield of 85%.

Melting point(MP):71-73℃; ¹ H NMR(400MHz,CDCl ₃ )δ8.02(s,1H),7.83-7.81(m,2H),7.77-7.74(m,2H),7.64-7.61 (m,2H),7.51-7.48(m,2H),7.43-7.40(m,1H),3.28-3.22(m,1H),1.76-1.60(m,2H),1.34(t,J＝8.0Hz ,3H),1.08-1.03(m,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ141.75,139.92,139.44,135.76,128.93,128.28,127.93,126.98,124.57,120.56,45.79,29.633,11.8 HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₈ H ₁₉ N ₃ S 309.1300; Found, 309.1299.

Example 38

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-6 and II-12 as raw materials.

III-39 is a white solid with a yield of 41%.

Melting point(MP):79-82℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.84–7.66(m,5H),7.47-7.42(m,2H),7.38(d,J＝8.0Hz,1H ),4.70(q,J=8.0Hz,1H),1.96–1.81(m,2H),1.59(s,2H),1.35–1.19(m,3H),0.92(t,J=8.0Hz,3H) . ¹³ C NMR (101MHz, CDCl ₃ ) δ137.86, 133.62, 133.17, 131.99, 128.72, 127.69, 127.26, 127.09, 126.61, 126.56, 125.96, 125.52, 57.79, 39.17, 21.258, 13.15 (HR-IES/MS.15 z) [M+H] ⁺ Calcd for C ₁₇ H ₁₉ N ₃ S 297.1300; Found, 297.1298.

Example 39

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-2 and II-13 as raw materials.

III-40 is a white solid with a yield of 77%.

Melting point(MP):74-77℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.65(s,1H),7.34(d,J＝8.0Hz,2H),7.15(d,J＝8.0Hz, 2H), 4.37(t, J=8.0Hz, 2H), 1.92(t, J=8.0Hz, 2H), 1.31–1.26(m, 10H), 0.88(t, J=8.0Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ137.36, 135.04, 132.04, 130.11, 127.46, 120.51, 50.79, 31.63, 30.12, 28.98, 28.86, 26.40, 22.56, 14.03.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₂₂ BrN ₃ S 367.0718; Found, 367.0715.

Example 40

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-3 and II-14 as raw materials.

III-41 is a white solid with a yield of 82%.

Melting point (MP): 84-86°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.61 (s, 1H), 7.30 (t, J = 8.0Hz, 2H), 7.24 (br, 5H), 7.15 ( d, J=8.0Hz, 2H), 4.37(t, J=8.0Hz, 2H), 2.66(t, J=8.0Hz, 2H), 2.30–2.23(m, 2H). ¹³ C NMR (101MHz, CDCl ₃ ) δ139.78,137.75,134.13,132.73,130.08,129.15,128.65,128.35,127.45,126.45,49.87,32.40,31.43. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₁₆ ClN ₃ S 329.0753; Found, 329.0752.

Example 41

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-9 and II-15 as raw materials.

III-42 is a white solid with a yield of 76%.

Melting point(MP):92-95℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.28–7.26(m,6H),7.18(d,J＝8.0Hz,2H),7.06(d,J＝8.0 Hz, 2H), 4.59(t, J=8.0Hz, 2H), 3.21(t, J=8.0Hz, 2H), 1.28(s, 9H). ¹³ C NMR(101MHz, CDCl ₃ ) δ149.95, 138.51, 136.68 ,131.86,128.98,128.79,128.61,127.62,127.09,126.05,51.90,36.54,34.40,31.18. HRMS-ESI(m/z)[M+H] ⁺ Calcdfor C ₂₀ H ₂₃ N ₃ S337.1613; Found, 337.1610.

Example 42

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-16 as raw materials.

III-43 is a white solid with a yield of 73%.

Melting point(MP):87-89℃; ¹ H NMR(400MHz,CDCl ₃ )δ7.64(s,1H),7.39-7.26(m,7H),7.07(d,J＝8.0Hz,2H), 6.67(d, J=12.0Hz, 1H), 6.36-6.29(m, 1H), 5.13(d, J=8.0Hz, 2H), 2.29(s, 3H). ¹³ C NMR(101MHz, CDCl ₃ )δ139 .91,137.09,135.89,135.31,131.57,129.94,129.87,128.76,128.68,126.74,126.53,121.32,52.69,20.99.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₈ H ₁₇ N ₃ S 307.1143; Found, 307.1142.

Example 43

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-17 as raw materials.

III-44 is a colorless liquid with a yield of 71%.

¹ H NMR (400MHz, CDCl ₃ ) δ7.57(s, 1H), 7.23(d, J=8.0Hz, 2H), 7.06(d, J=8.0Hz, 2H), 5.41(d, J=8.0Hz ,1H),5.06(d,J=8.0Hz,1H),4.94(d,J=8.0Hz,2H),2.29(s,3H),2.19(d,J=8.0Hz,2H),2.13(t ,J＝8.0Hz,2H),1.80(s,3H),1.67(s,3H),1.59(s,3H). ¹³ CNMR(101MHz,CDCl ₃ )δ143.66,139.02,136.81,132.78,131.95,129.77, 129.56,126.40,123.04,117.35,48.04,32.07,26.20,25.67,23.34,20.95,17.65. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₉ H ₂₅ N ₃ S 327.1769; Found, 327.1768 .

Example 44

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-18 as raw materials.

III-45 is a colorless liquid with a yield of 76%.

¹ H NMR (400MHz, CDCl ₃ ) δ7.58(s, 1H), 7.37-7.28(m, 4H), 7.26(d, J=3.2Hz, 1H), 7.23(d, J=8.2Hz, 2H) , 7.07(d, J=7.9Hz, 2H), 4.51(t, J=6.8Hz, 2H), 3.38(t, J=6.8Hz, 2H), 2.30(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ )δ139.39,137.04,133.59,131.56,130.58,129.86,129.79,129.37,127.48,127.37,49.61,34.15,20.98. HRMS-ESI(m/z)[ _M +H] ⁺ Calcdfor C ₁₃ H ₁₇ N S ₂ 327.0864; Found, 327.0860.

Example 45

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-2 and II-38 as raw materials.

III-46 is a white solid with a yield of 75%.

Melting point(MP):133-135℃; ¹ H NMR(400MHz,CDCl ₃ )δ8.05(s,1H),7.62(d,J＝8.0Hz,2H),7.40-7.35(m,4H), 7.23(d,J=8.0Hz,2H),2.54(t,J=12.2Hz,1H),1.96–1.86(m,4H),1.52–1.41(m,2H),1.35-1.21(m,10H) ,1.12-1.05(m,2H),0.90(t,J=8.0Hz,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ149.41,138.52,134.57,134.48,132.17,130.57,128.19,125.53,120.87,120.47 ,44.27,37.28,37.22,34.24,33.42,32.17,26.61,22.69,14.09. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₅ H ₃₀ BrN ₃ S 483.1344; Found, 483.1346.

Example 46

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-19 as raw materials.

III-47 is a colorless liquid with a yield of 72%.

¹ H NMR (400MHz, CDCl ₃ ) δ7.79(s, 1H), 7.23(d, J=8.0Hz, 2H), 7.06(d, J=7.9Hz, 2H), 4.53(dd, J=14.1, 3.3Hz, 1H), 4.37(dd, J＝14.1, 6.0Hz, 1H), 4.22(qd, J＝6.9, 3.3Hz, 1H), 3.77(m, 2H), 2.29(s, 3H), 2.09- 2.00(m,1H),1.86(dq,J=14.4,7.2Hz,1H),1.77-1.69(m,1H),1.59(dq,J=12.5,7.5Hz,1H). ¹³ C NMR(101MHz, CDCl ₃ )δ139.14,136.83,131.91,129.78,129.59,128.33,76.96,68.57,53.23,28.43,25.64,20.95. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₄ H ₁₇ N ₃ OS275 .1092; Found, 275.1090.

Example 47

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-20 as raw materials.

III-48 is a white solid with a yield of 78%.

Melting point(MP):98-101℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.30(s,1H),7.14(d,J＝8.0Hz,2H),7.05(d,J＝8.0Hz, 2H), 6.86(s, 1H), 6.76(d, J=8.0Hz, 1H), 6.64(d, J=8.0Hz, 1H), 4.53-4.50(m, 4H), 3.12-3.08(m, 4H ),2.28(s,3H) ^.13 C NMR(101MHz,CDCl ₃ )δ159.14,138.53,136.69,131.79,129.69,129.28,128.47,128.12,127.54,127.42,125.09,109.25,70.12,35.92 20.85. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₁₉ H ₁₉ N ₃ OS337.1249; Found, 337.1248. Example 48

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-21 as raw materials.

III-49 is a white solid with a yield of 83%.

Melting point (MP): 130-132℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.56(d, J＝1.9Hz, 1H), 7.13(d, J＝8.0Hz, 2H), 7.06–7.03( m,3H),7.00(s,1H),6.13(s,1H),4.88–4.84(m,2H),4.60–4.58(m,2H),2.30(s,3H). ¹³ C NMR(101MHz, CDCl ₃ )δ140.77,139.37,136.96,131.36,130.54,129.75,129.67,127.96,105.85,51.37,49.99,20.92. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₄ H ₁₅ N ₅ S 285.1048; Found, 285.1046.

Example 49

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-22 as raw materials.

III-50 is a white solid with a yield of 81%.

Melting point(MP):140-143℃; ¹ H NMR(400MHz, CDCl ₃ )δ8.52(d, J＝5.5Hz, 1H), 8.02(s, 1H), 7.89(d, J＝1.9Hz, 1H), 7.68(dd, J=5.5, 1.9Hz, 1H), 7.36(d, J=8.0Hz, 2H), 7.13(d, J=8.0Hz, 2H), 2.33(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ151.77, 143.92, 143.51, 143.34, 138.20, 131.16, 130.19, 129.68, 123.06, 117.67, 112.78, 21.07. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₁₄ H ₁₁ BrN ₄ S 345.9888; Found, 345.9887.

Example 50

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-1 and II-23 as raw materials.

III-51 is a white solid with a yield of 79%.

Melting point (MP): 130-132℃; ¹ H NMR (400MHz, CDCl ₃ ) δ8.54(d, J＝5.5Hz, 1H), 8.02(s, 1H), 7.74(d, J＝1.9Hz, 1H), 7.64(dd, J=5.5, 1.9Hz, 1H), 7.36(d, J=8.0Hz, 2H), 7.13(d, J=8.0Hz, 2H), 2.33(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ153.32, 151.45, 144.41, 143.37, 138.22, 131.19, 130.20, 129.68, 123.05, 114.02, 112.44, 21.08. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₁₄ H ₁₁ ClN ₄ S 302.0393; Found, 302.0392.

Example 51

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-9 and II-41 as raw materials.

III-52 is a yellow liquid with a yield of 63%.

¹ H NMR (400MHz, CDCl ₃ ) δ8.25(s, 1H), 7.66(s, 1H), 7.30(s, 4H), 7.21(d, J=8.3Hz, 1H), 6.97(d, J= 8.5Hz,1H),3.86(s,3H),2.36(s,3H),1.28(s,9H). ¹³ C NMR(101MHz,CDCl ₃ )δ149.94,148.69,138.00,132.13,131.04,130.57,129.55, 128.91,126.12,125.62,125.48,112.21,56.06,34.46,31.23,20.36. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₀ H ₂₃ N ₃ OS353.1562; Found, 353.1561.

Example 52

The structural formula of the target product is as follows:

The procedure is the same as in Example 17, using I-9 and II-42 as raw materials.

III-53 is a white solid with a yield of 72%.

Melting point(MP):68-70℃; ¹ H NMR(400MHz,CDCl ₃ )δ8.32(s,1H),7.47(s,1H),7.31(s,4H),7.02–6.95(m,2H ),3.83(d,J＝3.1Hz,6H),1.29(s,10H). ¹³ C NMR(101MHz,CDCl ₃ )δ153.86,149.94,144.58,138.15,131.95,129.44,128.93,126.08,115.80,113.58, 109.84,56.46,55.91,34.40,31.17. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₀ H ₂₃ N ₃ O ₂ S369.1511; Found, 369.1510.

Example 53

The structural formula of the target product is as follows:

At room temperature, add 0.3mmol III-52, 0.9mmol mCPBA and 1mL CH ₂ Cl ₂ to a 10mL reaction tube, react at room temperature for 15h, add saturated aqueous ammonium chloride solution and 10mL ethyl acetate for extraction and separation, and obtain by column chromatography Product IV-1, the yield is 90%.

Ⅳ-1 is white powder.

Melting point(MP):124-126℃; ¹ H NMR(400MHz,CDCl ₃ )δ8.69(s,1H),8.05(d,J＝8.7Hz,2H),7.60–7.56(m,3H), 7.24(d, J=8.5Hz, 1H), 6.99(d, J=8.5Hz, 1H), 3.89(s, 3H), 2.35(s, 3H), 1.33(s, 9H). ¹³ C NMR (101MHz ,CDCl ₃ )δ157.83,148.73,148.58,137.25,131.31,131.14,127.98,127.71,126.34,125.52,124.72,112.24,56.12,35.27,31.02,20.32.HRMS-[M+m/z ^] Calcd for C ₂₀ H ₂₃ N ₃ O ₃ S 385.1460; Found, 385.1459.

Example 54

The structural formula of the target product is as follows:

The procedure is the same as in Example 53, using III-53 as the raw material.

Ⅳ-2 is a white solid with a yield of 87%.

Melting point (MP): 151-154℃; ¹ H NMR (400MHz, CDCl ₃ ) δ8.76(s, 1H), 8.06(d, J＝8.6Hz, 2H), 7.57(d, J＝8.6Hz, 2H), 7.40(d, J=2.9Hz, 1H), 7.04(d, J=9.1Hz, 1H), 6.99(dd, J=9.1, 2.9Hz, 1H), 3.88(s, 3H), 3.80( s,3H),1.33(s,9H). ¹³ C NMR(101MHz,CDCl ₃ )δ157.86,153.89,148.87,144.58,137.21,127.99,127.70,126.33,125.26,116.53,113.57,110.13,556.98, , 29.99. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₀ H ₂₃ N ₃ O ₄ S401.1409; Found, 401.1408. Example 55

The structural formula of the target product is as follows:

At room temperature, add 1.1 mmol Ⅰ-8, 0.5 mmol azide Ⅱ-24, 0.05 mmol CuI, 0.75 mmol t-BuOK and 2 mL nPrOH into a 10 mL reaction tube, react at 110 °C for 12 h, cool to room temperature, add saturated chlorine Ammonium chloride aqueous solution and 10 mL of ethyl acetate were extracted and separated, and the product XII-1 was obtained by column chromatography with a yield of 76%.

Product XII-1 is a white powder.

Melting point(MP):132-135℃; ¹ H NMR(400MHz, CDCl ₃ )δ7.49(s,2H),7.28(s,4H),7.16(dd,J＝7.7,1.3Hz,2H), 7.13–7.10(m,2H),7.10–7.03(m,4H),5.53(s,4H),2.42(s,6H). ¹³ C NMR(101MHz,CDCl ₃ )δ139.29,137.44,135.11,134.24,130.41 ,129.61,128.78,127.02,126.98,126.65,53.89,20.33. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₆ H ₂₄ N ₆ S ₂ 484.1504; Found, 484.1503.

Example 56

The structural formula of the target product is as follows:

At room temperature, add 1.1mmol Ⅰ-1, 0.5mmol azide Ⅱ-25, 0.05mmol CuI, 0.75mmol t-BuOK, 0.05mmol DMEDA and 2mL nPrOH into a 10mL reaction tube, react at room temperature for 12h, add saturated chloride Aqueous ammonium solution and 10 mL of ethyl acetate were extracted and separated, and the product XII-3 was obtained by column chromatography with a yield of 76%.

Product XII-3 is a white powder with a yield of 72%.

Melting point (MP): 120-122°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.55 (s, 2H), 7.25 (d, J = 7.9

Hz, 4H), 7.07(d, J=7.9Hz, 4H), 4.31(t, J=7.1Hz, 4H), 2.29(s, 6H), 1.90–1.87(m, 4H), 1.36–1.32(m ,4H). ¹³ C NMR (101MHz, CDCl ₃ ) δ139.59, 137.10, 131.59, 129.87, 126.61, 50.29, 29.84, 25.71, 20.99. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₄ H ₂₈ N ₆ S ₂ 464.1817; Found, 464.1815.

Example 57

The structural formula of the target product is as follows:

At room temperature, add 0.5mmol Ⅰ-2, 0.6mmol azide Ⅱ-25, 0.05mmol CuI, 0.75mmol t-BuOK, 0.05mmol DMEDA and 2mL nPrOH into a 10mL reaction tube, react at room temperature for 12h, add saturated chloride Ammonium aqueous solution and 10 mL of ethyl acetate were extracted and separated, and the intermediate azide compound was obtained by column chromatography. Add 0.5mmol I-8, intermediate azide compound, 0.05mmol CuI, 0.75mmol t-BuOK, 0.05mmol DMEDA and 2mL nPrOH into a 10mL reaction tube, react at room temperature for 12h, add saturated ammonium chloride aqueous solution and 10mL ethyl acetate The ester was extracted and separated, and the product XII-4 was obtained by column chromatography. The yield was 59%.

Melting point (MP): 101-103℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.63(s, 1H), 7.55(s, 1H), 7.37(d, J＝8.0Hz, 2H), 7.18– 7.15(m,3H),7.13–7.04(m,3H),4.35(td,J＝7.1,1.5Hz,4H),2.45(s,3H),1.95-1.88(m,4H),1.38-1.34( m,4H) ^.13C NMR(101MHz,CDCl ₃ )δ138.42,137.66,137.26,134.81,134.50,132.06,130.33,129.36,127.41,127.02,126.88,126.60,120.65,50.37,290.82 HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₃ H ₂₅ BrN ₆ S ₂ 528.0765; Found, 528.0764.

Example 58

The structural formula of the target product is as follows:

At room temperature, add 0.5mmol Ⅰ-3, 0.6mmol azide Ⅱ-24, 0.05mmol CuI, 0.75mmol t-BuOK and 2mL nPrOH into a 10mL reaction tube, react at room temperature for 12h, add saturated aqueous ammonium chloride solution and 10mL Ethyl acetate was extracted and separated, and the intermediate azide compound was obtained by column chromatography. Add 0.5mmol I-2, intermediate azide compound, 0.05mmol CuI, 0.75mmol t-BuOK and 2mL nPrOH into a 10mL reaction tube, react at room temperature for 12h, add saturated aqueous ammonium chloride solution and 10mL ethyl acetate to extract and separate , the product XII-2 was obtained by column chromatography. The yield was 60%.

Melting point(MP):226-229℃; ¹ H NMR(400MHz,DMSO)δ8.60(d,J＝1.3Hz,2H),7.50(d,J＝8.6Hz,2H),7.38–7.34(m ,6H),7.19(d,J=8.0Hz,2H),7.12(d,J=8.0Hz,2H),5.64(s,4H). ¹³ C NMR(101MHz,DMSO)δ135.67,135.32,135.17,134.73 ,134.52,132.14,131.27,130.71,130.64,130.56,130.07,130.03,129.48,129.27,128.51,119.52,52.96. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₄ H ₁₈ BrClN _{6 2} 567.9906; Found, 567.9904.

Example 59

The structural formula of the target product is as follows:

At room temperature, add 0.3mmol Ⅰ-1, 0.45mmol azide Ⅱ-1, 0.015mmol Cu(MeCN) ₄ PF ₆ , 0.03mmol Na ascorbate and 2mL DMF to a 10mL reaction tube, react at 150°C for 15h, add saturated Ammonium chloride aqueous solution and 10 mL of ethyl acetate were extracted and separated, and the products V-1 and VI-1 were obtained by column chromatography, and the yields were 33% and 54%, respectively.

Ⅴ-1: Melting point (MP): 120-124°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.52-7.47 (m, 6H), 7.35-7.31 (m, 4H), 7.19 (d, J＝ 8.0Hz, 2H), 7.11-7.06(m, 3H), 6.99(d, J=8.0Hz, 2H), 6.93(d, J=8.0Hz, 2H), 6.10(s, 2H), 2.28(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ145.24(d, J=16.2Hz), 137.43, 134.87, 137.74(d, J=3.0Hz), 131.82(d, J=11.1Hz), 130.45, 130.14(d, J=114.2Hz), 129.63, 129.18, 128.52(d, J=13.1Hz), 128.41(d, J=111.2Hz), 128.34, 128.28, 128.02, 54.50, ^21.01.31 P NMR (162MHz, CDCl ₃ ) δ19.41.HRMS-ESI(m/z)[M+H] ⁺ Calcdfor C ₂₈ H ₂₄ N ₃ OPS481.1378; Found, 481.1377.

Ⅵ-1: Meltingpoint (MP): 93-95℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.79(m, 4H), 7.49(t, J=7.4Hz, 2H), 7.43-7.38(m, 4H), 7.26-7.21(m, 3H), 7.16-7.14(m, 2H), 6.90(d, J=8.1Hz, 2H), 6.83(d, J=8.0Hz, 2H), 5.52(s, 2H ), 2.21(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ144.72(d, J=130.4Hz), 137.92, 136.37(d, J=24.3Hz), 133.96, 132.00(d, J= 112.1Hz), 131.90, 131.78 (d, J=10.1Hz), 130.37, 129.98, 128.74, 128.37, 128.25, 128.01, 52.03, 20.95. ³¹ PNMR (162MHz, CDCl ₃ ) δ16.61.HRMS-ESI (m/ z) [M+H] ⁺ Calcd for C ₂₈ H ₂₄ N ₃ OPS481.1378; Found, 481.1376.

Example 60

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-1 and II-6 as raw materials.

Ⅴ-2 is a white solid with a yield of 32%. VI-2 is a yellow liquid with a yield of 52%.

Ⅴ-2: Melting point (MP): 106-109°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.51-7.42 (m, 6H), 7.35–7.26 (m, 6H), 7.23 (d, J＝ 8.0Hz, 2H), 7.02(d, J=8.0Hz, 2H), 6.97(d, J=8.0Hz, 2H), 6.15(s, 2H), 2.30(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ )δ145.96(d, J=15.2Hz), 138.66, 137.77, 132.95(d, J=2.0Hz), 131.72(d, J=11.1Hz), 130.82, 129.78(d, J=115.2Hz) ,129.74,129.48(d,J=112.2Hz),129.21,128.78,128.67,128.54(d,J=2.0Hz),126.56(q,J=261.8Hz),125.20(q,J=4.0Hz),54.00 ,21.05. ³¹ P NMR (162MHz, CDCl ₃ ) δ19.33. ¹⁹ F NMR (376MHz, CDCl ₃ ) δ-62.76. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₉ H ₂₃ F ₃ N ₃ OPS 549.1252; Found, 549.1251.

Ⅵ-2: ¹ H NMR (400MHz, CDCl ₃ ) δ7.86-7.79(m, 4H), 7.52(t, J=7.4Hz, 2H), 7.47-7.40(m, 6H), 7.15(d, J ＝8.0Hz, 2H), 6.83(d, J＝8.3Hz, 2H), 6.78(d, J＝8.1Hz, 2H), 5.59(s, 2H), 2.19(s, 3H). ¹³ C NMR (101MHz , CDCl ₃ ) δ145.35(d, J=131.4Hz), 138.10, 137.62, 136.38(d, J=23.2Hz), 132.49, 132.02, 131.79(d, J=111.2Hz), 131.76(d, J= 10.1Hz), 130.78(q, J=36.4Hz), 130.06(d, J=19.2Hz), 128.67(d, J=14.2Hz), 128.38(d, J=12.1Hz), 127.98, 125.56(d, J=4.0Hz), 123.77 (d, J=275.7Hz), 51.32, 20.78. ³¹ P NMR (162MHz, CDCl ₃ ) δ16.61. ¹⁹ F NMR (376MHz, CDCl ₃ ) δ-62.74.HRMS-ESI ( m/z)[M+H] ⁺ Calcd for C ₂₉ H ₂₃ F ₃ N ₃ OPS 549.1252; Found, 549.1250.

Example 61

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-3 and II-1 as raw materials.

Ⅴ-3 is a white solid with a yield of 30%. VI-3 is a colorless liquid with a yield of 51%.

Ⅴ-3: Melting point (MP): 118-123°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.51-7.45 (m, 6H), 7.30-7.34 (m, 4H), 7.20 (d, J＝ 7.5Hz, 2H), 7.13-7.07(m, 5H), 6.87(d, J＝8.6Hz, 2H), 6.12(s, 2H). ¹³ C NMR (101MHz, CDCl ₃ ) δ143.53(d, J =16.2Hz), 134.69, 133.12, 132.84(d, J=4.0Hz), 131.74(d, J=11.1Hz), 130.53, 129.93(d, J=115.2Hz), 129.58(d, J=109.2Hz) ,128.90,128.54(d,J＝14.2Hz),128.35,128.33,128.13,54.62. ³¹ P NMR(162MHz,CDCl ₃ )δ19.28.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₇ H ₂₁ ClN ₃ OPS 501.0831; Found, 501.0832.

Ⅵ-3: Melting point (MP): 98-101℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.79-7.74 (m, 4H), 7.51 (t, J＝7.8Hz, 2H), 7.44-7.40 (m,4H),7.26-7.22(m,3H),7.15(d,J=7.0Hz,2H),6.92(d,J=8.8Hz,2H),6.85(d,J=6.7Hz,2H) ,5.59(s,2H) ^.13 C NMR(101MHz,CDCl ₃ )δ145.24(d,J=131.4Hz),135.46,133.80(d,J=16.2Hz),132.27,132.06,131.69(d,J =10.1Hz), 131.14, 129.86 (d, J=128.4Hz), 128.85, 128.52, 128.40 (d, J=12.1Hz), 127.95, 52.22. ³¹ P NMR (162MHz, CDCl ₃ ) δ16.40.HRMS- ESI(m/z)[M+H] ⁺ Calcd for C ₂₇ H ₂₁ ClN ₃ OPS501.0831; Found, 501.0830.

Example 62

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-6 and II-1 as raw materials.

Ⅴ-4 is a white solid with a yield of 27%. VI-4 is a yellow liquid with a yield of 47%.

Ⅴ-4: Melting point (MP): 85-87℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.75-7.73 (m, 1H), 7.63-7.58 (m, 2H), 7.51-7.41 (m, 8H),7.31(s,1H),7.25-7.20(m,6H),7.13-7.04(m,4H),6.15(s,2H). ¹³ CNMR(101MHz,CDCl ₃ )δ143.96(d,J =15.2Hz), 134.85, 132.76(d, J=3.0Hz), 132.74(d, J=124.4Hz), 131.80(d, J=11.1Hz), 130.73, 130.34, 129.98(d, J=114.2Hz) , _{129.26,128.50} (d,J ^＝ 13.1Hz),128.47,128.35,128.33,128.11,127.90,127.63,127.27,126.79,126.55,126.12,54.65. (m/z)[M+H] ⁺ Calcdfor C ₃₁ H ₂₄ N ₃ OPS, 517.1378; Found, 517.1375.

Ⅵ-4: ¹ H NMR (400MHz, CDCl ₃ ) δ7.79-7.74(m, 4H), 7.68(d, J=8.0Hz, 1H), 7.47(d, J=8.7Hz, 1H), 7.45- 7.38(m, 5H), 7.34-7.30(m, 5H), 7.17(s, 5H), 6.99(d, J=10.5Hz, 1H), 5.58(s, 2H). ¹³ C NMR (101MHz, CDCl ₃ )δ145.23(d, J=133.5Hz), 135.62(d, J=23.2Hz), 133.79, 132.76(d, J=108.2Hz), 131.89, 131.67(d, J=10.1Hz), 131.11, 129.23 , 129.01, 128.92, 128.69, 128.41, 128.24 (d, J=13.1Hz), 128.01, 127.56, 127.39, 126.69, 126.65, 126.48, 52.21. ³¹ P NMR (162MHz, CDCl ₃ ) δ16.68.HRMS-ESI ( m/z)[M+H] ⁺ Calcd for C ₃₁ H ₂₄ N ₃ OPS, 517.1378; Found, 4517.1374.

Example 63

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-1 and II-15 as raw materials.

Ⅴ-5 is a yellow solid with a yield of 27%. VI-5 is a yellow liquid with a yield of 48%.

Ⅴ-5: Melting point (MP): 96-98℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.66-7.56(m, 6H), 7.44-7.42(m, 4H), 7.23-7.16(m, 5H), 6.98(d, J=4.0Hz, 2H), 6.88(d, J=12.0Hz, 2H), 5.09(t, J=8.0Hz, 2H), 3.17(t, J=8.0Hz, 2H) ,2.29(s,3H) ^.13 C NMR(101MHz,CDCl ₃ )δ144.48(d,J=16.2Hz),137.22,136.93,132.96(d,J=3.0Hz),131.90(d,J=11.1 Hz), 130.42(d, J=114.2Hz), 129.99, 129.61, 128.99, 128.98(d, J=110.2Hz), 128.74(d, J=13.1Hz), 128.51, 126.75, 52.49, 37.12, ^20.99.31 P NMR (162MHz, CDCl ₃ ) δ19.04. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₉ H ₂₆ N ₃ OPS, 495.1534; Found, 495.1532.

Ⅵ-5: ¹ H NMR (400MHz, CDCl ₃ ) δ7.82-7.77(m,4H),7.55-7.49(m,2H),7.46-7.41(m,4H),7.28-7.22(m,3H) ,7.05(d,J=5.8Hz,2H),7.01(d,J=8.2Hz,2H),6.93(d,J=8.0Hz,2H),4.54(t,J=8.0Hz,2H),3.07 (t, J=8.0Hz, 2H), 2.24(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ144.46(d, J=134.5Hz), 138.13, 136.63, 136.18(d, J=23.2 Hz), 132.04(d, J=111.2Hz), 131.95, 131.80(d, J=10.1Hz), 130.30(d, J=27.3Hz), 128.72, 128.52, 128.34(d, J=13.1Hz), 127.03 ^. _{_} ^_ _{_ _ _}

Example 64

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-1 and II-14 as raw materials.

Ⅴ-6 is a yellow liquid with a yield of 25%. VI-6 is a yellow liquid with a yield of 47%.

Ⅴ-6: ¹ H NMR (400MHz, CDCl ₃ ) δ7.68-7.63(m,4H),7.60-7.57(m,2H),7.47-7.42(m,4H),7.24-7.21(m,2H) ,7.17-7.16(m,1H),7.04(d,J=4.0Hz,2H),7.00(d,J=8.0Hz,2H),6.94(d,J=8.0Hz,2H),4.86(t, J＝8.0Hz, 2H), 2.55(t, J＝8.0Hz, 2H), 2.28(s, 3H), 2.17-2.09(m, 2H). ¹³ C NMR (101MHz, CDCl ₃ ) δ144.95(d ,J=16.2Hz),140.58,137.42,133.02(d,J=3.0Hz),131.92(d,J=11.1Hz),130.40(d,J=114.2Hz),130.39,129.67,129.39,128.80(d , J=13.1Hz), 128.66 (d, J=111.2Hz), 128.34, 128.33, 126.00, 51.19, 32.52, 32.17, 21.02. ³¹ P NMR (162MHz, CDCl ₃ ) δ18.75.HRMS-ESI (m/ z) [M+H] ⁺ Calcd for C ₃₀ H ₂₈ N ₃ OPS, 509.1691; Found, 509.1694.

Ⅵ-6: ¹ H NMR (400MHz, CDCl ₃ ) δ7.86-7.81(m, 4H), 7.52(t, J=6.7Hz, 2H), 7.46-7.42(m, 4H), 7.28-7.24(m ,2H),7.19(t,J=7.3Hz,1H),7.09(d,J=8.8Hz,2H),6.97(d,J=8.3Hz,2H),6.91(d,J=8.1Hz,2H ), 4.30(t, J=7.4Hz, 2H), 2.57(t, J=7.6Hz, 2H), 2.23(s, 3H), 2.05(q, J=8.0Hz, 2H). ¹³ C NMR (101MHz , CDCl ₃ )δ140.04, 138.17, 131.96, 131.95 (d, J=111.2Hz), 131.93, 131.75 (d, J=10.1Hz), 130.66, 130.10, 128.43, 128.39, 128.32, 128.27, 126.19, 327.8 30.87,20.95. ³¹ P NMR(162MHz,CDCl ₃ )δ16.89.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₃₀ H ₂₈ N ₃ OPS,509.1691; Found,509.1693.

Example 65

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-7 and II-14 as raw materials.

Ⅴ-7 is a yellow liquid with a yield of 26%. VI-7 is a yellow liquid with a yield of 45%.

Ⅴ-7: ¹ H NMR (400MHz, CDCl ₃ ) δ7.67-7.61(m, 4H), 7.56(t, J=8.0Hz, 2H), 7.44-7.40(m, 4H), 7.25-7.21(m ,2H),7.16((t,J=8.0Hz,1H),7.06-7.03(m,3H),6.96(d,J=8.0Hz,1H),6.77(d,J=8.0Hz,1H), 6.73(s,1H),4.89(t,J=8.0Hz,2H),2.56(t,J=8.0Hz,2H),2.22(s,3H),2.19-2.11(m,2H). ¹³ C NMR (101MHz, CDCl ₃ ) δ143.93(d, J=16.2Hz), 140.56, 138.61, 133.18, 132.96(d, J=3.0Hz), 131.90(d, J=11.1Hz), 130.32(d, J= 114.2Hz), 129.88, 129.62(d, J=110.2Hz), 128.74(d, J=13.1Hz), 128.36, 128.33, 127.86, 126.43, 126.02, 51.26, 32.54, 32.22, 21.23. ³¹ PNMR(162MHz, CDCl ₃ ) δ18.91.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₃₀ H ₂₈ N ₃ OPS, 509.1691; Found, 509.1696.

Ⅵ-7: ¹ H NMR (400MHz, CDCl ₃ ) δ7.87-7.82(m, 4H), 7.52(t, J=7.8Hz, 2H), 7.47-7.42(m, 4H), 7.28-7.25(m ,4H),7.19(t,J=7.3Hz,1H),7.10(d,J=7.4Hz,2H),7.01(t,J=7.6Hz,1H),6.94(d,J=7.6Hz,1H ), 6.83(d, J=7.6Hz, 1H), 6.77(s, 1H), 4.30(t, J=7.4Hz, 2H), 2.59(t, J=7.6Hz, 2H), 2.13(s, 3H ),2.11-2.05(m,2H) ^.13 C NMR(101MHz,CDCl ₃ )δ139.97,139.29,131.97,131.94,131.92(d,J=111.2Hz),131.72(d,J=10.1Hz),130.22, 129.10, 128.58, 128.40, 128.30 (d, J=12.1Hz), 128.26, 126.82, 126.71, 47.86, 32.43, 30.80, 21.09.31 PNMR (162MHz, CDCl ₃ ) ^δ16.78 . HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₃₀ H ₂₈ N ₃ OPS, 509.1691; Found, 509.1697.

Example 66

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-12 and II-1 as raw materials.

Ⅴ-8 is a yellow liquid with a yield of 28%. VI-8 is a yellow liquid with a yield of 49%.

Ⅴ-8: ¹ H NMR (400MHz, CDCl ₃ ) δ7.56-7.51(m, 6H), 7.41-7.37(m, 4H), 7.18(d, J=7.8Hz, 2H), 7.14-7.04(m ,3H),6.04(s,2H),2.93(t,J=7.4Hz,2H),1.46(q,J=7.2Hz,2H),1.21(br,10H),0.87(t,J=6.9Hz ,3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ148.14(d, J=16.2Hz), 134.96, 132.68(d, J=3.0Hz), 131.86(d, J=11.1Hz), 130.26(d ,J=115.2Hz),128.52(d,J=13.1Hz),128.29,128.08(d,J=29.3Hz),125.37,124.25,54.31,32.84,31.71,29.36,29.07,28.97,28.60,22.56,14.03 . ³¹ P NMR (162MHz, CDCl ₃ ) δ18.74. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₉ H ₃₄ N ₃ OPS503.2160; Found, 503.2159.

Ⅵ-8: ¹ H NMR (400MHz, CDCl ₃ ) δ7.88-7.82(m, 4H), 7.52(t, J=7.3Hz, 2H), 7.47-7.46(m, 4H), 7.30(br, 5H ),5.65(s,2H),2.76(t,J=7.6Hz,2H),1.23-1.14(m,8H),1.04(br,4H),0.87(t,J=7.1Hz,3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ143.66(d, J=136.5Hz), 138.25(d, J=24.3Hz), 134.54, 132.23(d, J=117.3Hz), 131.93, 131.70(d, J= 11.1Hz), 128.80, 128.32 (d, J=13.1Hz), 127.90, 51.86, 37.13, 31.62, 29.46, 28.95, 28.85, 28.39, 22.51, 14.00. ³¹ P NMR (162MHz, CDCl ₃ ) δ16.89.HRMS -ESI(m/z)[M+H] ⁺ Calcd for C ₂₉ H ₃₄ N ₃ OPS503.2160; Found, 503.2161.

Example 67

The structural formula of the target product is as follows:

The procedure is the same as in Example 59, using I-11 and II-1 as raw materials.

Ⅴ-9 is a yellow liquid with a yield of 30%. VI-9 is a yellow liquid with a yield of 47%.

Ⅴ-9: ¹ H NMR (400MHz, CDCl ₃ ) δ7.55-7.51(m, 6H), 7.41-7.36(m, 4H), 7.19(d, J=7.1Hz, 2H), 7.12-7.06(m ,3H),6.06(s,2H),3.52-3.44(m,1H),1.50(dq,J=13.9,7.0Hz,1H),1.40(dq,J=14.1,7.0Hz,1H),1.10( d, J＝6.8Hz, 3H), 0.82(t, J＝7.4Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ147.72(d, J＝16.2Hz), 135.09, 132.66(d, J =3.0Hz), 131.92(dd, J=11.1, 4.0Hz), 130.34(dd, J=114.2, 2.0Hz), 128.47(dd, J=13.1, 2.0Hz), 128.29, 128.09(d, J=32.3 Hz), 125.64 (d, J=125.6Hz), 54.33, 44.52, 29.46, 20.43, 11.11. ³¹ P NMR (162MHz, CDCl ₃ ) δ19.12. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₅ H ₂₆ N ₃ OPS 447.1534; Found, 447.1533.

Ⅵ-9: ¹ H NMR (400MHz, CDCl ₃ ) δ7.88-7.83(m,4H),7.52-7.50(m,2H),7.47-7.43(m,4H),7.30(br,5H),5.64 (s,2H),3.55(q,J=6.7Hz,1H),1.44-1.29(m,2H),0.96(d,J=6.8Hz,3H),0.76(t,J=7.4Hz,3H) . ¹³ C NMR (101MHz, CDCl ₃ ) δ143.66(d, J=136.5Hz), 138.02(d, J=23.2Hz), 133.70(d, J=168.8Hz), 131.91(d, J=2.0Hz ), 131.70 (dd, J=10.1, 5.0Hz), 128.77, 128.42, 128.32 (dd, J=13.1, 5.0Hz), 127.99, 51.71, 48.42, 29.57, 19.85, 10.89. ³¹ P NMR (162MHz, CDCl ₃ )δ16.69.HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₅ H ₂₆ N ₃ OPS447.1534; Found, 447.1530.

Example 68

The structural formula of the target product is as follows:

At room temperature, add 0.3mmol I-1, 0.9mmol mCPBA and 2mL CH ₂ Cl ₂ into a 10mL reaction tube, react at room temperature for 15h, add saturated ammonium chloride aqueous solution and 10mL ethyl acetate for extraction and separation, dry and filter to obtain intermediate Crude product. At room temperature, add the above intermediate crude product, 0.45mmol II-1 and 1mL DMF into a 10mL reaction tube, react at 120°C for 30h, add saturated ammonium chloride aqueous solution and 10mL ethyl acetate for extraction and separation, dry filter, pass through the column layer The products VII-1 and VIII-1 were obtained as white solids by analysis, and the yields were 30% and 52%, respectively.

Ⅶ-1: Melting point (MP): 187-189℃; ¹ H NMR (400MHz, CDCl ₃ ) δ7.71-7.65 (m, 4H), 7.59 (br, 2H), 7.44–7.42 (m, 4H) ,7.34–7.32(m,2H),7.18(br,4H),7.14–7.03(m,3H),6.25(s,2H),2.39(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ152 .42(d, J=13.1Hz), 145.10, 136.29, 134.42, 132.94(d, J=3.0Hz), 132.42(d, J=11.1Hz), 129.62(d, J=117.3Hz), 129.51, 129.16 ^[ _{_} M+H] ⁺ Calcd for C ₂₈ H ₂₄ N ₃ O ₃ PS 513.1276; Found, 513.1275.

Ⅷ-1: Melting point (MP): 167-169℃; ¹ HNMR (400MHz, CDCl ₃ ) δ7.90 (d, J = 8.0Hz, 2H), 7.79–7.74 (m, 4H), 7.54-7.53 ( m,2H),7.49-7.45(m,4H),7.29(d,J=8.0Hz,1H),7.22(d,J=8.0Hz,2H),7.08-7.04(m,4H),5.97(s ,2H),2.32(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ145.65,144.12(d,J=125.4Hz),142.15(d,J=20.2Hz),135.75,133.64,132.06(d, J=3.0Hz), 131.98(d, J=111.4Hz), 131.88(d, J=10.1Hz), 129.62, 129.09, 128.84, 128.41, 128.32(d, J=13.1Hz), 127.58, 53.85, 21.64. ³¹ P NMR (162MHz, CDCl ₃ ) δ18.13. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₈ H ₂₄ N ₃ O ₃ PS 513.1276; Found, 513.1273.

Example 69

The structural formula of the target product is as follows:

The procedure is the same as in Example 68, using I-11 and II-9 as raw materials.

VII-2 is a white solid with a yield of 32%. VIII-2 is a white solid with a yield of 39%.

Ⅶ-2: Melting point (MP): 192-194℃; ¹ H NMR (400MHz, CDCl ₃ ) δ8.18–8.15(m,1H),7.79-7.77(m,1H),7.71–7.65(m, 4H),7.63–7.56(m,3H),7.49-7.45(m,2H),7.43-7.38(m,6H),7.19(d,J＝8.0Hz,2H),7.01(d,J＝8.0Hz ,1H),6.90(d,J=7.1Hz,1H),6.73(s,2H),2.39(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ152.38(d,J=12.1Hz) ,145.16,136.23,133.50,133.02,132.42(d,J=11.1Hz),130.79,130.31,129.40(d,J=117.3Hz),129.06,128.96(d,J=114.2Hz),128.48,128.47(d , J = 14.2Hz), 126.68 (d, J = 6.1Hz), 125.94, 124.82, 123.28, 52.70, 21.66. ³¹ P NMR (162MHz, CDCl ₃ ) δ 21.84. HRMS-ESI (m/z) [M +H] ⁺ Calcd for C ₃₂ H ₂₆ N ₃ O ₃ PS 563.1432; Found, 563.1431.

Ⅷ-2: Melting point (MP): 174-176°C; ¹ HNMR (400MHz, CDCl ₃ ) δ7.92 (d, J=9.1Hz, 1H), 7.88 (d, J=9.1Hz, 1H), 7.83 (d, J=7.5Hz, 2H), 7.80(d, J=7.8Hz, 4H), 7.72(d, J=8.3Hz, 1H), 7.59-7.55(m, 4H), 7.52-7.48(m, 4H), 7.02(t, J=7.7Hz, 1H), 6.90(d, J=8.0Hz, 2H), 6.41(s, 2H), 6.34(d, J=7.2Hz, 1H), 2.27(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ145.71, 135.03, 132.98 (d, J=109.2Hz), 132.12, 131.85 (d, J=10.1Hz), 130.80 (d, J=101.1Hz), 129.57, 129.04, 128.88, 128.76(d, J=10.1Hz), 128.36(d, J=13.1Hz), 127.09, 126.31, 125.08, 124.89, 122.27, 51.25, 21.62. ³¹ P NMR(162MHz, CDCl ₃ ) δ18.42 .HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₃₂ H ₂₆ N ₃ O ₃ PS563.1432; Found, 563.1429.

Example 70

The structural formula of the target product is as follows:

At room temperature, add 0.3mmol V-1, 1.2mmol PhSiH ₃ , 3.0mmol acetic acid and 2mL toluene to a 10mL reaction tube, react at 120°C for 12h, add saturated ammonium chloride aqueous solution and 10mL ethyl acetate for extraction and separation, and dry Filtration and column chromatography yielded product IX.

IX, white solid, the yield is 91%. Melting point(MP):105-108℃; ¹ HNMR(400MHz,CDCl ₃ )δ7.29–7.25(m,2H),7.21-7.14(m,11H),7.10(d,J＝8.0Hz,2H) ,6.99–6.94(m,4H),5.72(s,2H),2.26(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ146.38,136.83,135.00,133.20(d,J＝25.3Hz),133.08 (d, J=20.2Hz), 131.72(d, J=4.0Hz), 130.41, 129.95(d, J=99.1Hz), 128.64(d, J=108.2Hz), 128.55, 128.78, 128.77, 53.65(d , J=10.1Hz), 21.00. ³¹ P NMR (162MHz, CDCl ₃ ) δ-34.99. HRMS-ESI (m/z) [M+H] ⁺ Calcd for C ₂₈ H ₂₄ N ₃ PS 465.1429; Found, 465.1427 .

Example 71

The structural formula of the target product is as follows:

At room temperature, 0.3mmol V-1, 0.33mmol MeMgBr (3.0M in EthylEther) and 1mL THF were added to a 10mL reaction tube, and the reaction was carried out at room temperature for 5h, and aromatic aldehyde 1 (0.45mmol) was added in THF ( 1 mL) solution, reacted at room temperature for 15 h, added saturated aqueous ammonium chloride solution and 10 mL ethyl acetate for extraction and separation, dried and filtered, and obtained product X-1 by column chromatography.

Ⅹ-1, white solid, the yield is 66%. Melting point(MP):150-152℃; ¹ HNMR(400MHz, CDCl ₃ )δ7.75(d, J＝8.0Hz, 1H), 7.62(d, J＝8.0Hz, 1H), 7.55(d, J ＝8.0Hz,1H),7.48–7.41(m,3H),7.20(d,J＝8.0Hz,2H),7.11–7.06(m,4H),7.01–6.97(m,4H),6.43(s, 1H),5.46–5.36(m,2H),2.25(s,3H). ¹³ C NMR(101MHz,CDCl ₃ )δ140.44,137.01,136.16,134.51,132.90,132.83,131.67,129.89,129.45,128.51,128.47 128.05, 128.03, 127.57, 127.53, 126.32, 124.62, 123.39, 66.18, 53.14, 20.94. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₂₇ H ₂₃ N ₃ OS437.1562; Found, 437.1561.

Example 72

The structural formula of the target product is as follows:

The procedure is the same as in Example 71, using V-1 and aromatic aldehyde 2 as raw materials.

X-2 is a white solid, the yield is 52%.

Ⅹ-2: Melting point (MP): 163-165°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.80 (d, J = 8.0Hz, 1H), 7.61 (s, 1H), 7.46 (t, J =8.0Hz,1H),7.39(d,J=8.0Hz,1H),7.24-7.20(m,3H),7.19(s,1H),7.16(d,J=1.8Hz,1H),7.14-7.11 (m,3H),7.03-6.99(m,4H),6.44(s,1H),5.43(s,2H),4.32(q,J=7.2Hz,2H),2.22(s,3H),1.41( t, J＝7.2Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ141.18, 140.22, 139.49, 137.06, 136.90, 134.71, 131.83, 129.86, 129.35, 128.53, 128.02, 127.559, 125.942, 123.2 ,120.55,118.95,117.90,108.51,108.43,66.91,53.09,37.56,20.90,13.79. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₃₁ H ₂₈ N ₄ OS 504.1984; Found, 504.1983.

Example 73

The structural formula of the target product is as follows:

At room temperature, add 0.3mmol VI-1, 2mLTHF and 0.33mmol MeMgBr (3.0MinEthyl Ether) into a 10mL reaction tube, and react at room temperature for 10h, add saturated aqueous ammonium chloride solution and 10mL ethyl acetate for extraction and separation, dry and filter, pass The product XI-1 was obtained by column chromatography.

Ⅺ-1, colorless liquid, yield 92%. ¹ H NMR (400MHz, CDCl ₃ )δ7.76(s,1H),7.25(s,2H),7.18-7.17(m,2H),7.02(d,J=8.0Hz,2H),6.97(d, J＝8.1Hz,2H),5.51(s,2H),2.29(s,3H). ¹³ CNMR(101MHz,CDCl ₃ )δ139.24,137.80,134.53,130.21,129.25,129.08,129.00,128.68,128.18,127.86, 51.89,20.95. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₆ H ₁₅ N ₃ S281.0987; Found, 281.0988.

Example 74

The structural formula of the target product is as follows:

The procedure is the same as in Example 73, using VI-8 as the raw material.

Ⅺ-2 is a yellow liquid with a yield of 90%.

Ⅺ-2: ¹ H NMR (400MHz, CDCl ₃ ) δ7.67(s, 1H), 7.35-7.29(m, 3H), 7.28-7.24(m, 2H), 5.58(s, 2H), 2.52(t ,J=7.4Hz,2H),1.49-1.42(m,2H),1.27-1.21(m,10H),0.88(t,J=6.9Hz,3H). ¹³ CNMR(101MHz,CDCl ₃ )δ137.46,135.02 ,130.01,128.76,128.25,127.67,51.66,35.36,31.65,29.14,28.99,28.86,28.29,22.53,14.00. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₇ H ₂₅ N ₃ S 303.1769; Found, 303.1767.

Example 75

The structural formula of the target product is as follows:

The procedure is the same as in Example 73, using VI-9 as the raw material.

Ⅺ-3 is a white solid with a yield of 86%.

Ⅺ-3: Melting point (MP): 61-63°C; ¹ H NMR (400MHz, CDCl ₃ ) δ7.70 (s, 1H), 7.35-7.28 (m, 5H), 5.61 (s, 2H), 2.66 (q, J=6.7Hz, 1H), 1.56-1.40(m, 2H), 1.13(d, J=6.7Hz, 3H), 0.91(t, J=7.4Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ )δ138.96,135.22,129.37,128.79,128.28,127.73,51.64,47.01,29.41,20.36,11.22. HRMS-ESI(m/z)[M+H] ⁺ Calcd for C ₁₃ H ₁₇ N ₃ S 247.1143; Found ,247.1142.

Claims (9)

1. A class of thio1,2,3-triazoles and its efficient synthesis method, characterized in that: using diphenylphosphonothioalkyne I and azide compound II as raw materials, through different reactions, efficient A simple method for the synthesis of sulfur-containing 1,2,3-triazole compounds Ⅲ-Ⅻ. The structural formula is as follows:

2. The synthetic method according to claim 1, characterized in that, phenylphosphonothioalkyne I is the following compound:

3. The synthetic method according to claim 1, wherein the azide compound II is one of the following compounds:

4. The synthesis method according to claim 1, characterized in that the copper catalyst cat.1 is one of the following compounds: cuprous iodide (CuI), tetraacetonitrile copper hexafluorophosphonate (Cu(MeCN) ₄ PF ₆ )one. 5. synthetic method according to claim 1 is characterized in that, alkaline reagent is potassium tert-butoxide (tBuOK). 6. The synthetic method according to claim 1, characterized in that the organic amine is N,N'-dimethylethylenediamine (DMEDA). 7. The synthesis method according to claim 1, characterized in that the copper catalyst cat.2 is one of the following copper catalysts: one of CuI, Cu(MeCN) ₄ BF ₄ , CuI/CuSO ₄ -5H ₂ O. 8. synthetic method according to claim 1, is characterized in that, Grignard reagent is methylmagnesium bromide (MeMgBr). 9. synthetic method according to claim 1, is characterized in that, aromatic aldehyde is one of following compounds:

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