CN111333651B - SCF-containing3Or SeCF3Heterocyclic compounds of (5) and process for preparing the same - Google Patents

SCF-containing3Or SeCF3Heterocyclic compounds of (5) and process for preparing the same Download PDF

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CN111333651B
CN111333651B CN202010155172.1A CN202010155172A CN111333651B CN 111333651 B CN111333651 B CN 111333651B CN 202010155172 A CN202010155172 A CN 202010155172A CN 111333651 B CN111333651 B CN 111333651B
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徐涛
徐显弘
赵楠
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Ocean University of China
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Abstract

The invention discloses a method for preparing a high-purity Silicon Carbide (SCF) containing Silicon Carbide (SCF)3Or SeCF3After the chloro heterocyclic compound 1 is dissolved in an EtOH solution, 1.0-2.0 times of equivalent of thiourea or selenourea is added, and then the mixture is stirred for 1-8 hours at the temperature of 50-120 ℃ to react to obtain a compound 2; dissolving the compound 2 in Acetone or EA solution, and adding 2.0-4.0 times of equivalent of CF3SO2Na, 0.2-0.4 equivalent of Cu salt, then dropwise adding 2.0-4.0 equivalent of tBuOOH solution, reacting at 25-40 deg.C for 1.0-2.0 hr to obtain compound 3, i.e. the required SCF-containing3Or SeCF3The heterocyclic compound of (1). The compound synthesized by the method has great potential in treating diseases, each step of the synthetic route can be amplified, the yield can reach 85%, the synthetic route provided by the invention brings a simpler and more effective way for synthesizing the compound with biological activity, the yield is high, the compound can be prepared in a large scale, and the method has a very wide application prospect.

Description

SCF-containing3Or SeCF3Heterocyclic compounds of (5) and process for preparing the same
Technical Field
The invention relates to a method for producing a polymer containing SCF3Or SeCF3And a process for producing the same.
Background
Containing SCF3Or SeCF3The heterocyclic compound is a very important pharmaceutical chemical intermediate and has very high application value. It is widely found in all organisms, where adenine and guanine are essential components of all nucleic acids, and form DNA and RN with thymine and cytosineFour bases of the a molecule. In addition, they play an important role in energy supply, metabolic regulation, coenzyme composition, and disease treatment. The purine drugs have significant therapeutic effects on acute lymphocytic leukemia, rheumatoid arthritis, ulcerative colitis/Crohn's disease, central nervous system diseases (CNS) such as multiple sclerosis, systemic lupus erythematosus, asthma, allograft rejection/graft-versus-host disease (GVHD), psoriasis, atopic dermatitis, eczema, urticaria, allergic rhinitis, myasthenia gravis, diabetes, idiopathic thrombocytopenic purpura, glomerulonephritis, cardiovascular diseases and cancer. The trifluoromethylthio group or the trifluoromethylseleno group is introduced into the molecule, the lipid solubility of the molecule can be adjusted in different ranges, the cell permeability of the molecule is properly increased, the cell metabolism and the biological activity of the molecule are effectively improved, and the effects of oxidation resistance, cancer resistance, bacteria resistance and virus resistance are obvious.
In recent years, organic chemists have been in the C-SCF3Much work is done on the construction of keys. However, with respect to C-SeCF3Few studies of bond construction have been reported, although SeCF3Such as SCF3May also have potential biological activity. Various methods have been used to synthesize SCF-containing polymers3In contrast, trifluoromethylselenylation is much less likely because the selenium species are generally very toxic and unstable to air or water.
Due to C-SeCF3Bond formation is challenging, and the synthesis of the trifloxyselenated heterocyclic compound reported previously is mainly obtained by coupling reaction catalyzed by transition metal by using boric acid and aryl halide as substrates. But more complex to prepare containing SCF3Or SeCF3The heterocyclic compounds of (a) still have certain difficulties and the adaptability of the substrate is not wide enough.
Disclosure of Invention
To solve the above technical problems, the present invention provides a SCF-containing polymer3Or SeCF3To a process for the preparation thereof, to enable large-scale preparation of SCF-containing compounds3Or SeCF3Heterocyclic compounds of (2)The purpose of (1).
In order to achieve the purpose, the technical scheme of the invention is as follows:
SCF-containing3Or SeCF3The heterocyclic compound of (a), which has the following general formula:
Figure BDA0002403775650000021
wherein Y ═ S or Se;
x ═ C or N;
a ═ C or N;
B＝N；
e ═ C or N;
R1methyl, ethyl, isopropyl, isobutyl, benzyl, ethan-1-ol, cyclopropylmethyl, allyl, propargyl, (2, 2-dimethyltetrahydrofuran [3,4-d ]][1,3]Dioxazol-4-yl) methanol, 2- (acetoxymethyl) tetrahydrofuran-3, 4-diacetic acid diacetate, ethyl 2- ((1H-imidazol-1-yl) methoxy) acetate, 2- ((1H-imidazol-1-yl) methoxy) propane-1, 3-diacetic acid diacetate, and the like alkyl groups;
R2h, cyclohexyl or benzyl, and similar alkyl groups;
R3h, amines or acetamides and similar alkyl groups;
R4me, Et or Bn and similar alkyls.
Preferably, the compound is selected from the compounds of the following structures:
Figure BDA0002403775650000022
Figure BDA0002403775650000031
SCF-containing3Or SeCF3The process for preparing a heterocyclic compound of (1), comprising the steps of:
(1) dissolving the chloro heterocyclic compound 1 in an EtOH solution, adding 1.0-2.0 times of equivalent of thiourea or selenourea, and then stirring for 1-8 hours at 50-120 ℃ to react to obtain a compound 2;
(2) dissolving the compound 2 in Acetone or EA solution, and adding 2.0-4.0 times of equivalent of CF3SO2Na, 0.2-0.4 equivalent of Cu salt, then dropwise adding 2.0-4.0 equivalent of tBuOOH solution, reacting at 25-40 deg.C for 1.0-2.0 hr to obtain compound 3, i.e. the required SCF-containing3Or SeCF3The heterocyclic compound of (1);
the specific reaction process is as follows:
Figure BDA0002403775650000032
in the above scheme, in the step (1), thiourea or selenourea in an amount of 1.5 times equivalent to that of the chloro-heterocyclic compound 1 is added at 100 ℃.
In the scheme, in the step (1), after the reaction is finished, the reaction product is directly filtered, and the precipitate is washed by anhydrous EtOH and is dried in a spinning mode to obtain the compound 2.
In the above scheme, in the step (2), 2.0 times equivalent of CF is added to Acetone or EA solution of the compound 2 at 40 deg.C3SO2Na, 0.2 equivalents of Cu salt, then 2.0 equivalents of tBuOOH solution were added dropwise.
In the above scheme, in the step (2), after the reaction is completed, the reaction solution is concentrated under reduced pressure and purified by silica gel column chromatography to obtain the compound 3.
Through the technical scheme, the invention provides the SCF-containing gas3Or SeCF3The preparation method of the heterocyclic compound has high applicability and can be widely applied to the synthesis of different substituted heterocyclic compounds. In contrast to previous studies, the present invention provides synthetic SCF-containing compositions3Or SeCF3The heterocyclic compound has the advantages of more environment-friendly reagent, simpler and more convenient operation, high yield and large-scale production. The trifluoromethylthio group or the trifluoromethylseleno group is introduced into the molecule, and the lipid solubility of the molecule can be adjusted in different ranges so as to properly increase the cell permeability of the moleculeFinally, the metabolism and the biological activity of the molecular cells are effectively improved, and the antioxidant, anticancer, antibacterial and antiviral effects are remarkable.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below.
The invention provides a method for preparing a high-purity SCF3Or SeCF3The preparation method of the heterocyclic compound of (4) includes the following specific examples:
example 1:
Figure BDA0002403775650000041
to a solution of compound 1b (338mg,2.0mmol) in EtOH (10mL) was added commercial thiourea (228mg,3mmol) and the reaction heated to 100 deg.C and stirred at reflux for 3 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain Compound 2b, 317mg (white solid) in a yield of 95%.
1H NMR(400MHz,DMSO-d6)δ8.23(s,1H),8.19(s,1H),3.75(s,3H).13C NMR(100MHz,DMSO-d6)δ176.2,145.4,145.0,144.2,120.3,30.4.HRMS calcd.For C6H5N4S-[M-H]-:165.0240.Found:165.0232.
Figure BDA0002403775650000051
A solution of Compound 2b in Acetone was prepared, and CF was added to a solution of Compound 2b (83mg,0.5mmol) in Acetone (3mL)3SO2Na (156mg, 1.0mmol), CuI (19mg,0.1mmol), then tBuOOH solution (160. mu.L, 1.0mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3b, 79mg (colorless oil), with a yield of 68%.
3b:Rf＝0.5(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.90(s,1H),8.11(s,1H),3.93(s,3H).13C NMR(100MHz,Chloroform-d)δ152.4,152.0,145.0,132.4,128.2(q,J＝307Hz),30.3.19F NMR(376MHz,Chloroform-d)δ-37.53.HRMS calcd.For C7H6F3N4S+[M+H]+:235.02598.Found:235.02603.
Example 2:
Figure BDA0002403775650000052
to a solution of compound 1c (169mg,1.0mmol) in EtOH (10mL) was added commercial thiourea (114mg,1.5mmol), and the reaction was heated to 100 ℃ and stirred under reflux for 2 h. After the reaction was finished by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain Compound 2c in a yield of 66% as 110mg (white solid).
1H NMR(400MHz,DMSO-d6)δ8.39(s,1H),8.13(s,1H),4.19(s,3H).13C NMR(100MHz,DMSO-d6)δ170.9,153.3,149.0,145.4,126.4,35.3.HRMS calcd.For C6H5N4S-[M-H]-:165.02349.Found:165.02404.
Figure BDA0002403775650000061
A solution of Compound 2c in Acetone was prepared and CF was added to a solution of Compound 2c (90mg,0.54mmol) in Acetone (3mL)3SO2Na (169mg, 1.08mmol), CuI (19mg,0.108mmol), then tBuOOH solution (170. mu.L, 1.08mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3c, 72mg (yellow oil), yield 57%.
3c:Rf＝0.3(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ9.07(s,1H),8.28(s,1H),4.15(s,3H).13C NMR(100MHz,Chloroform-d)δ161.2,153.0,150.2,141.2,128.1(q,J＝309Hz),126.3,34.9.19F NMR(376MHz,Chloroform-d)δ-37.72.HRMS calcd.For C7H6F3N4S+[M+H]+:235.02653.Found:235.02598.
Example 3:
Figure BDA0002403775650000062
to a solution of compound 1d (184mg,1.0mmol) in EtOH (10mL) was added commercial thiourea (114mg,1.5mmol), and the reaction was heated to 50 ℃ and stirred at reflux for 2 h. After the reaction was finished by TCL detection, the reaction solution was filtered, and the precipitate was washed with anhydrous EtOH, and then dried by spinning to obtain Compound 2d, 180mg (white solid) in 99% yield.
1H NMR(400MHz,DMSO-d6)δ8.31(s,1H),8.19(s,1H),4.19(q,J＝7.3Hz,2H),1.40(t,J＝7.3Hz,3H).13C NMR(100MHz,DMSO-d6)δ176.3,145.3,144.5,143.3,135.6,39.2,15.8.HRMS calcd.For C7H9N4S+[M+H]+:181.05424.Found:181.05421.
Figure BDA0002403775650000071
A solution of Compound 2d in Acetone was prepared, and CF was added to a solution of Compound 2d (181mg,1.0mmol) in Acetone (3mL)3SO2Na (312mg, 2.0mmol), CuI (38mg,0.2mmol), then tBuOOH solution (340. mu.L, 2.0mmol) was added dropwise and reacted at 30 ℃ for 1.0 hour. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3d, 151mg (white solid) in 62% yield.
3d:Rf＝0.6(Hex:Ethyl Acetate＝1:2)
1H NMR(400MHz,Chloroform-d)δ8.88(s,1H),8.12(s,1H),4.36(q,J＝7.3Hz,2H),1.58(t,J＝7.3Hz,3H).13C NMR(100MHz,Chloroform-d)δ152.2,151.9,144.2,132.5,128.2(q,J＝309Hz),39.6,15.4.19F NMR(376MHz,Chloroform-d)δ-37.53.HRMS calcd.For C8H8N4F3S+[M+H]+:249.04163.Found:249.04161.
Example 4:
Figure BDA0002403775650000072
to a solution of compound 1e (262mg,1.4mmol) in EtOH (10mL) was added commercially available thiourea (162mg,2.1mmol), and the reaction was heated to 110 deg.C and refluxed with stirring for 2 hours. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain Compound 2e in a yield of 180mg (white solid) at 71%.
1H NMR(400MHz,DMSO-d6)δ8.50(s,1H),8.16(s,1H),4.71(q,J＝7.1Hz,2H),1.41(t,J＝7.1Hz,3H).13C NMR(100MHz,DMSO-d6)δ170.3,153.7,148.2,145.4,125.7,42.3,18.3.HRMS calcd.For C7H9N4S+[M+H]+:181.05424.Found:181.05432.
Figure BDA0002403775650000081
A solution of Compound 2e in Acetone was prepared and CF was added to a solution of Compound 2e (60mg,0.3mmol) in Acetone (3mL)3SO2Na (94mg,0.6mmol), CuI (11mg,0.06mmol), then tBuOOH solution (100. mu.L, 0.6mmol) was added dropwise and reacted at 25 ℃ for 2.0 hours. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3e, 36mg (yellow oil) in 49% yield.
3e:Rf＝0.4(Hex:Ethyl Acetate＝1:2)
1H NMR(400MHz,Chloroform-d)δ9.06(s,1H),8.35(s,1H),4.50(q,J＝7.3Hz,2H),1.59(t,J＝7.3Hz,3H).13C NMR(100MHz,Chloroform-d)δ152.8,149.0,141.4,132.5,128.1(q,J＝309Hz),42.9,16.8.19F NMR(376MHz,Chloroform-d)δ-37.41.HRMS calcd.For C8H8N4F3S+[M+H]+:249.04163.Found:249.04163.
Example 5:
Figure BDA0002403775650000082
to a solution of compound 1j (600mg,3.0mmol) in EtOH (10mL) was added commercial thiourea (342mg,4.5mmol), and the reaction was heated to 120 ℃ and stirred at reflux for 2 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain 2j, 150mg (white solid) in a yield of 25%.
1H NMR(400MHz,DMSO-d6)δ8.24(s,1H),8.19(s,1H),5.02(s,1H),4.20(t,J＝5.2Hz,2H),3.72(d,J＝10.2Hz,2H).13C NMR(100MHz,DMSO-d6)δ176.1,145.3,144.8,144.1,135.5,59.7,46.7.HRMS calcd.For C7H8ON4NaS+[M+Na]+:219.0311.Found:219.0312.
Figure BDA0002403775650000083
A solution of Compound 2j in Acetone was prepared and CF was added to a solution of Compound 2j (140mg,0.7mmol) in Acetone (3mL)3SO2Na (387mg, 1.4mmol), CuI (27mg,0.14mmol) and tBuOOH solution (400. mu.L, 1.4mmol) were added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3j, 150mg (yellow oil) in 81% yield.
3j:Rf＝0.3(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,DMSO-d6)δ8.92(s,1H),8.64(s,1H),4.35(t,J＝5.2Hz,2H),3.79(t,J＝5.2Hz,2H).13C NMR(100MHz,DMSO-d6)δ152.2,151.0,149.2,148.4,132.1,128.9(q,J＝308Hz),59.4,47.0.19F NMR(376MHz,DMSO-d6)δ-36.84.HRMS calcd.For C8H8N4F3OS+[M+H]+:265.0365.Found:265.0367.
Example 6:
Figure BDA0002403775650000091
to a solution of compound 1k (150mg,0.7mmol) in EtOH (5mL) was added commercial thiourea (80mg,1.05mmol), and the reaction was heated to 100 deg.C and stirred at reflux for 3 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain 2k, 122mg (white solid) in 83% yield.
1H NMR(400MHz,DMSO-d6)δ8.31(s,1H),8.16(s,1H),4.01–3.96(m,2H),1.28-1.20(m,1H),0.50-0.46(m,2H),0.40-0.38(m,2H).13C NMR(100MHz,DMSO-d6)δ176.3,145.4,144.5,143.4,135.5,48.3,11.9,4.3.HRMS calcd.For C9H11N4S+[M+H]+:207.0699.Found:207.0703.
Figure BDA0002403775650000092
A solution of Compound 2k in Acetone was prepared and CF was added to a solution of Compound 2k (90mg,0.4mmol) in Acetone (3mL)3SO2Na (125mg, 0.8mmol), CuI (15mg,0.08mmol), then tBuOOH solution (130. mu.L, 0.8mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3k, 59mg (white solid) in a yield of 54%.
3k:Rf＝0.6(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.87(s,1H),8.19(s,1H),4.16–4.12(m,2H),1.38–1.30(m,1H),0.73–0.68(m,2H),0.49(dd,J＝5.6,4.2Hz,2H).13C NMR(100MHz,Chloroform-d)δ152.2,151.8,150.3,144.3,132.1,128.4(q,J＝308Hz),49.0,11.1,4.5.19F NMR(376MHz,Chloroform-d)δ-37.52.HRMS calcd.For C10H10N4F3S+[M+H]+:275.0573.Found:275.0576.
Example 7:
Figure BDA0002403775650000101
1l of compound in EtOH was prepared, and to 1l (280mg,1.4mmol) of compound in EtOH (5mL) was added commercially available thiourea (152mg,2.1mmol), and the reaction was heated to 100 ℃ and stirred under reflux for 2 hours. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and spin-dried to obtain 2l of compound (267 mg, white solid) in 98% yield.
1H NMR(400MHz,DMSO-d6)δ8.27(s,1H),8.19(s,1H),6.09-6.02(m,1H),5.22(d,J＝10.3Hz,1H),5.10–5.00(m,1H),4.85–4.78(m,2H).13C NMR(100MHz,DMSO-d6)δ176.4,145.6,144.6,143.5,135.4,133.5,118.3,46.0.HRMS calcd.For C8H9N4S+[M+H]+:193.0542.Found:193.0546.
Figure BDA0002403775650000102
A solution of compound 2l in Acetone was prepared and CF was added to a solution of compound 2l (193mg,1.0mmol) in Acetone (3mL)3SO2Na (624mg, 4.0mmol), CuI (76mg,0.4mmol), then tBuOOH solution (640. mu.L, 4.0mmol) was added dropwise and reacted at 25 ℃ for 2.0 hours. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain 3l of compound (121 mg) (colorless oil) in 46% yield.
3l:Rf＝0.6(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.89(s,1H),8.08(s,1H),6.04(ddt,J＝16.4,10.2,5.8Hz,1H),5.37(d,J＝10.1Hz,1H),5.26(d,J＝17.1Hz,1H),4.90(d,J＝5.8Hz,2H).13C NMR(100MHz,Chloroform-d)δ152.3,152.1,150.2,144.5,131.9,131.0,128.3(q,J＝309Hz),120.1,46.2.19F NMR(376MHz,Chloroform-d)δ-37.52.HRMS calcd.For C9H8N4F3S+[M+H]+:261.0416.Found:261.0421.
Example 8:
Figure BDA0002403775650000111
to a solution of compound 1m in EtOH (5mL) was added commercial thiourea (114mg,1.5mmol) and the reaction was heated to 100 ℃ and stirred at reflux for 3 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and spin-dried to obtain 2m of compound (191 mg as a white solid) in a yield of 98%.
1H NMR(400MHz,DMSO-d6)δ8.34(s,1H),8.23(s,1H),5.07(s,2H),3.54-3.52(m,1H).13C NMR(100MHz,DMSO-d6)δ176.5,145.9,144.3,142.9,135.4,78.2,77.0,33.5.HRMS calcd.For C8H4N4S+[M+H]+:191.0386.Found:191.0389.
Figure BDA0002403775650000112
A solution of Compound 2m in Acetone was prepared, and CF was added to a solution of Compound 2m (172mg,0.9mmol) in Acetone (3mL)3SO2Na (562mg, 3.6mmol), CuI (68mg,0.36mmol), then tBuOOH solution (600. mu.L, 3.6mmol) was added dropwise and reacted at 25 ℃ for 2.0 hours. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3m, 130mg (white solid) in a yield of 56%.
3m:Rf＝0.8(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.90(s,1H),8.29(s,1H),5.05(d,J＝2.6Hz,2H),2.57(t,J＝2.5Hz,1H).13C NMR(100MHz,Chloroform-d)δ152.5,152.4,143.8,140.9,132.0,128.2(q,J＝307Hz),76.0,75.1,33.6.19F NMR(376MHz,Chloroform-d)δ-37.50.HRMS calcd.For C9H6N4F3S+[M+H]+:259.0260.Found:259.0264.
Example 9:
Figure BDA0002403775650000121
to a solution of compound 1n (286mg,1.0mmol) in EtOH (5mL) was added commercial thiourea (114mg,1.5mmol), and the reaction was heated to 50 deg.C and stirred at reflux for 8 h. After the reaction was finished by TCL detection, the reaction solution was filtered, and the precipitate was washed with anhydrous EtOH, and then dried by spinning to obtain 2n, 239mg (white solid) and 85% yield.
1H NMR(400MHz,DMSO-d6)δ8.57(s,1H),8.23(s,1H),5.91–5.86(m,1H),4.67(d,J＝36.8Hz,1H),4.47(t,J＝5.2Hz,1H),4.36–4.20(m,1H),4.13(d,J＝4.1Hz,1H),3.95(d,J＝3.8Hz,1H),3.66(dd,J＝12.1,3.9Hz,1H),3.56(dd,J＝12.0,3.9Hz,1H),3.43(q,J＝7.1Hz,1H).13C NMR(100MHz,DMSO-d6)δ176.5,145.9,144.4,141.7,135.8,88.1,86.1,74.8,70.6,61.6.HRMS calcd.For C10H11O4N4S-[M-H]-:283.0507.Found:283.0510.
Figure BDA0002403775650000122
A solution of Compound 2n in Acetone was prepared and CF was added to a solution of Compound 2n (100mg,0.35mmol) in Acetone (3mL)3SO2Na (109mg, 0.7mmol), CuI (13mg,0.07mmol), then tBuOOH solution (110. mu.L, 0.7mmol) was added dropwise,the reaction was carried out at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3n, 51mg (colorless oil) in 37% yield.
3n:Rf＝0.6(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.85(s,1H),8.22(s,1H),5.98(d,J＝4.5Hz,1H),5.22–5.17(m,1H),5.13–5.08(m,1H),4.56–4.52(m,1H),3.99–3.93(m,1H),3.81(dd,J＝12.6,2.0Hz,1H),1.64(s,3H),1.37(s,3H).13C NMR(100MHz,Chloroform-d)δ153.8,151.8,148.8,144.2,133.1,128.0(q,J＝309Hz),114.5,94.2,86.4,83.3,81.6,63.3,27.6,25.3.19F NMR(376MHz,Chloroform-d)δ-37.48.HRMS calcd.For C14H14N4F3O4S-[M-H]-:391.0693.Found:391.0692.
Example 10:
Figure BDA0002403775650000131
to a solution of compound 1o (140mg,0.55mmol) in EtOH (5mL) was added commercial thiourea (84mg,1.1mmol), and the reaction was heated to 100 ℃ and stirred under reflux for 8 hours. After the reaction was finished by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and spin-dried to obtain 2o, 90mg (white solid) of compound in 66% yield.
1H NMR(400MHz,DMSO-d6)δ8.14(s,1H),3.70(s,3H),2.93(t,J＝13.1Hz,1H),1.91(d,J＝12.4Hz,2H),1.81(d,J＝10.1Hz,2H),1.75–1.69(m,1H),1.62–1.52(m,2H),1.41(s,2H),1.30–1.22(m,1H).13C NMR(100MHz,DMSO-d6)δ174.7,158.7,145.6,144.8,134.5,35.8,31.2,29.1,26.0,19.1.HRMS calcd.For C12H16N4NaS+[M+Na]+:271.0988.Found:271.0989.
Figure BDA0002403775650000132
A solution of Compound 2O in Acetone was prepared and CF was added to a solution of Compound 2O (70mg,0.3mmol) in Acetone (3mL)3SO2Na (188mg, 1.2mmol), CuI (22mg,0.12mmol), then tBuOOH solution (200. mu.L, 1.2mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3o, 49mg (colorless oil) in 52% yield.
3o:Rf＝0.7(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.79(s,1H),3.82(s,3H),2.88(tt,J＝11.9,3.3Hz,1H),2.00–1.91(m,4H),1.79(q,J＝10.7,9.3Hz,4H),1.45–1.38(m,2H).13C NMR(100MHz,Chloroform-d)δ161.9,151.9,151.3,149.2,132.0,128.6(q,J＝308Hz),36.9,30.9,28.8,26.0,25.6.19F NMR(376MHz,Chloroform-d)δ-37.58.HRMS calcd.For C13H16N4F3S+[M+H]+:317.1042.Found:317.1046.
Example 11:
Figure BDA0002403775650000141
to a solution of compound 1s (170mg,0.7mmol) in EtOH (5mL) was added commercial thiourea (84mg,1.1mmol), and the reaction was heated to 120 ℃ and stirred under reflux for 4 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain Compound 2s, 112mg (white solid) in a yield of 67%.
1H NMR(400MHz,DMSO-d6)δ8.19(s,2H),7.32–7.23(m,3H),7.22–7.17(m,2H),5.49(s,2H).13C NMR(100MHz,DMSO-d6)δ179.4,147.6,147.2,137.3,137.0,129.2,128.3,128.1,117.8,50.9.HRMS calcd.For C12H9N4S-[M-H]-:241.0553.Found:241.0549.
Figure BDA0002403775650000142
A solution of Compound 2s in Acetone was prepared, and CF (CF) was added to a solution of Compound 2s (90mg,0.37mmol) in Acetone (3mL)3SO2Na (115mg, 0.74mmol), CuI (13mg,0.07mmol), then tBuOOH solution (120. mu.L, 0.74mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3s, 74mg (colorless oil) in 65% yield.
3s:Rf＝0.8(Hex:Ethyl Acetate＝3:1)
1H NMR(400MHz,Chloroform-d)δ8.91(s,1H),8.08(s,1H),7.35–7.30(m,5H),5.66(s,2H).13C NMR(100MHz,Chloroform-d)δ156.2,154.5,151.9,135.7,131.6,128.9,128.4,128.3,128.0(q,J＝308Hz),113.3,51.4.19F NMR(376MHz,Chloroform-d)δ-37.28.HRMS calcd.For C13H10N4F3S+[M+H]+:311.0572.Found:311.0575.
Example 12:
Figure BDA0002403775650000151
to a solution of compound 1t (147mg,0.6mmol) in EtOH (5mL) was added commercially available thiourea (69mg,0.9mmol), and the reaction was heated to 120 ℃ and stirred under reflux for 4 h. After the reaction was finished by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain 2t, 82mg (yellow solid) as a 57% yield.
1H NMR(400MHz,DMSO-d6)δ8.81(s,1H),7.98(s,1H),7.35–7.28(m,5H),5.49(s,2H).13C NMR(100MHz,DMSO-d6)δ181.9,153.9,146.0,136.5,132.1,129.2,128.8,128.7,117.8,57.0.HRMS calcd.For C12H9N4S-[M-H]-:241.0553.Found:241.0549.
Figure BDA0002403775650000152
A solution of Compound 2t in Acetone was prepared, and CF was added to a solution of Compound 2t (70mg,0.29mmol) in Acetone (3mL)3SO2Na (90mg, 0.58mmol), CuI (11mg,0.058mmol), then tBuOOH solution (100. mu.L, 0.58mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3t, 54mg (colorless oil) in a yield of 60%.
3t:Rf＝0.8(Hex:Ethyl Acetate＝3:1)
1H NMR(400MHz,Chloroform-d)δ8.96(s,1H),7.96(s,1H),7.39(h,J＝4.4,3.9Hz,5H),5.62(s,2H).13C NMR(100MHz,Chloroform-d)δ158.4,158.2,154.7,138.8,133.7,129.4,128.9,127.8(q,J＝308Hz),122.9,112.5,58.9.19F NMR(376MHz,Chloroform-d)δ-37.34.HRMS calcd.For C13H10N4F3S+[M+H]+:311.0572.Found:311.0575.
Example 13:
Figure BDA0002403775650000161
to a solution of compound 1u (259mg,1.0mmol) in EtOH (5mL) was added commercial thiourea (152mg,2.0mmol), and the reaction was heated to 120 ℃ and stirred at reflux for 2 hours. After the reaction was finished by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and spin-dried to obtain 2u, 176mg (white solid) of compound with a yield of 69%.
1H NMR(400MHz,DMSO-d6)δ8.21(s,1H),8.02(d,J＝8.1Hz,1H),7.77(d,J＝8.3Hz,1H),7.53(t,J＝7.7Hz,1H),7.40(t,J＝7.7Hz,1H),4.37(d,J＝7.5Hz,2H),2.08(hept,J＝6.9Hz,1H),0.87(d,J＝6.6Hz,6H).13C NMR(100MHz,DMSO-d6)δ176.5,146.0,140.7,137.4,129.4,129.1,124.6,122.0,117.8,114.3,54.0,28.9,19.8.HRMS calcd.For C14H16N3S+[M+H]+:258.1059.Found:258.1063.
Figure BDA0002403775650000162
A solution of compound 2u in Acetone was prepared, and CF (CF) was added to a solution of compound 2u (154mg,0.6mmol) in Acetone (3mL)3SO2Na (187mg, 1.2mmol), CuI (23mg,0.12mmol), then tBuOOH solution (200. mu.L, 1.2mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3u, 109mg (white solid) in a yield of 56%.
3u:Rf＝0.8(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.25(dd,J＝8.2,1.5Hz,1H),8.05(dd,J＝8.1,1.5Hz,1H),7.89(s,1H),7.71–7.60(m,2H),4.33(d,J＝7.4Hz,2H),2.33(dt,J＝13.7,6.9Hz,1H),1.03(d,J＝6.6Hz,6H).13C NMR(100MHz,Chloroform-d)δ145.0,144.7,143.9,136.8,132.6,131.1,129.2(q,J＝308Hz),127.9,127.2,120.1,117.6,55.3,28.9,19.9.19F NMR(376MHz,Chloroform-d)δ-38.10.HRMS calcd.For C15H15N3F3S+[M+H]+:326.0933.Found:326.0937.
Example 14:
Figure BDA0002403775650000171
to a solution of compound 1z (329mg,1.0mmol) in EtOH (5mL) was added commercial thiourea (114mg,1.5mmol), and the reaction was heated to 80 ℃ and stirred at reflux for 3 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain 2z, 191mg (yellow solid) in 58% yield.
1H NMR(400MHz,DMSO-d6)δ12.06(s,1H),8.34(s,1H),5.50(s,2H),4.06(s,2H),3.69(s,2H),2.21(s,3H),1.94(s,3H).13C NMR(100MHz,DMSO-d6)δ174.6,174.5,17.8,148.1,145.9,143.3,132.2,73.2,67.4,63.2,24.4,21.1.
Figure BDA0002403775650000172
A solution of compound 2z in Acetone was prepared and CF was added to a solution of compound 2z (100mg,0.3mmol) in Acetone (3mL)3SO2Na (94mg,0.6mmol), CuI (11mg,0.06mmol), then tBuOOH solution (100. mu.L, 0.6mmol) was added dropwise and reacted at 35 ℃ for 2.0 hours. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3z, 86mg (yellow solid) in 73% yield.
3z:Rf＝0.3(Hex:Ethyl Acetate＝2:1)
1H NMR(400MHz,Chloroform-d)δ8.32(s,1H),8.11(s,1H),5.63(s,2H),4.19(s,2H),3.79(s,2H),2.58(s,3H),2.02(s,3H).13C NMR(100MHz,Chloroform-d)δ171.4,170.9,153.4,152.7,151.6,144.2,128.0(q,J＝308Hz),127.9,73.4,68.4,62.9,25.4,21.0.19F NMR(376MHz,Chloroform-d)δ-37.46.HRMS calcd.For C13H14N5F3O4NaS+[M+Na]+:416.0616.Found:416.0611.
Example 15:
Figure BDA0002403775650000181
to a solution of compound 1aa (401mg,1.0mmol) in EtOH (5mL) was added commercial thiourea (114mg,1.5mmol), and the reaction was heated to 60 ℃ and stirred under reflux for 3 h. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 2aa, 153mg (yellow solid) in a yield of 38%.
1H NMR(400MHz,DMSO-d6)δ12.04(s,1H),8.33(s,1H),5.56(s,2H),4.09(dd,J＝11.4,3.1Hz,2H),4.04(dt,J＝7.0,3.5Hz,1H),3.96(dd,J＝11.3,6.0Hz,2H),2.22(s,3H),1.87(s,6H).13C NMR(100MHz,DMSO-d6)δ174.6,174.6,170.6,148.1,145.9,143.3,132.4,74.9,72.6,63.3,24.4,20.8.HRMS calcd.For C15H19N5NaO6S+[M+Na]+:420.0948.Found:420.0947.
Figure BDA0002403775650000182
A solution of Compound 2aa in Acetone was prepared and CF was added to a solution of Compound 2aa (120mg,0.3mmol) in Acetone (3mL)3SO2Na (94mg,0.6mmol), CuI (11mg,0.06mmol), then tBuOOH solution (100. mu.L, 0.6mmol) was added dropwise and reacted at 40 ℃ for 1.5 hours. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3aa, 93mg (colorless oil) in 67% yield.
3aa:Rf＝0.3(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.23(s,1H),8.09(s,1H),5.68(s,2H),4.20–4.14(m,2H),4.12–4.03(m,3H),2.57(s,3H),1.96(s,6H).13C NMR(100MHz,Chloroform-d)δ171.2,170.6,153.4,152.8,151.4,144.0,128.0(q,J＝308Hz),127.8,75.4,72.2,63.1,25.3,20.7.19F NMR(376MHz,Chloroform-d)δ-37.47.HRMS calcd.For C16H18F3N5NaO6S+[M+Na]+:488.0822.Found:488.0825.
Example 16:
Figure BDA0002403775650000191
to a solution of compound 1ab (415mg,1mmol) in EtOH (10mL) was added commercially available thiourea (114mg,1.5mmol), and the reaction was heated to 100 ℃ and stirred under reflux for 8 hours. After the reaction was completed by TCL detection, the reaction mixture was filtered, and the precipitate was washed with anhydrous EtOH, followed by spin-drying to obtain compound 2ab in a yield of 75% in 307mg (white solid).
1H NMR(400MHz,DMSO-d6)δ8.47(s,1H),8.21(s,1H),6.17(d,J＝5.5Hz,1H),5.86(t,J＝5.7Hz,1H),5.52–5.48(m,1H),4.38–4.32(m,2H),4.22(dd,J＝12.6,6.4Hz,1H),2.08(s,3H),1.99(d,J＝3.6Hz,6H).13C NMR(100MHz,DMSO-d6)δ176.8,170.6,169.9,169.8,146.1,144.2,142.3,136.2,86.2,80.2,72.8,70.5,63.3,21.0,20.9,20.7.HRMS calcd.For C16H18N4NaO7S+[M+Na]+:433.0788.Found:433.07890.
Figure BDA0002403775650000192
A solution of Compound 2ab in Acetone was prepared, and CF (2 ab (140mg,0.34 mmol)) was added to a solution of Compound 2ab in Acetone (3mL)3SO2Na (106mg, 0.68mmol), CuI (13mg,0.07mmol), then tBuOOH solution (110. mu.L, 0.68mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3ab, 103mg (colorless oil), with a yield of 63%.
3ab:Rf＝0.7(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.86(s,1H),8.23(s,1H),6.21(d,J＝5.1Hz,1H),5.92(t,J＝5.3Hz,1H),5.64–5.60(m,1H),4.47–4.34(m,3H),2.13(s,3H),2.09(s,3H),2.05(s,3H).13C NMR(100MHz,Chloroform-d)δ170.4,169.7,169.5,152.8,152.5,149.7,143.1,132.5,128.2(q,J＝308Hz),86.8,80.6,70.6,63.0,20.8,20.6,20.4.19F NMR(376MHz,Chloroform-d)δ-37.53.HRMS calcd.For C17H17 F3N4NaO7S+[M+Na]+:501.0662.Found:501.0663.
Example 17:
Figure BDA0002403775650000201
to a solution of compound 1ad (244mg,1.0mmol) in EtOH (5mL) was added commercial selenourea (123mg,1.0mmol), and the reaction was heated to 120 ℃ and stirred at reflux for 2 h. After the reaction was finished by TCL detection, the reaction solution was filtered, and the precipitate was washed with anhydrous EtOH, and then dried by spinning to obtain 2ad, 235mg (pale green solid) with a yield of 82%.
1H NMR(400MHz,DMSO-d6)δ8.57(s,1H),8.25(s,1H),7.32(q,J＝6.7Hz,5H),5.41(s,2H).13C NMR(100MHz,DMSO-d6)δ174.3,146.3,144.7,143.7,139.4,136.8,129.3,128.5,128.1,47.2.HRMS calcd.For C12H9N4Se-[M-H]-:288.9998.Found:288.9996.
Figure BDA0002403775650000202
A solution of Compound 2ad in EA was prepared, and CF was added to a solution of Compound 2ad (57mg,0.2mmol) in EA (3mL)3SO2Na (62mg, 0.4mmol), Cu (3mg,0.04mmol) and tBuOOH solution (70. mu.L, 0.4mmol) were added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3ad, 53mg (white solid) in a yield of 75%.
3ad:Rf＝0.8(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.90(s,1H),8.07(s,1H),7.42–7.29(m,5H),5.45(s,2H).13C NMR(100MHz,Chloroform-d)δ152.8,152.7,149.6,144.3,134.6,133.7,129.4,129.0,128.1,122.2(q,J＝330Hz),47.8.19F NMR(376MHz,Chloroform-d)δ-31.33.HRMS calcd.For C13H10N4F3Se+[M+H]+:359.0017.Found:359.0019.
Example 18:
Figure BDA0002403775650000211
to a solution of compound 1ae (122mg,0.5mmol) in EtOH (5mL) was added commercially available selenourea (62mg,0.5mmol), and the reaction was heated to 70 ℃ and stirred at reflux for 2 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain Compound 2ae, 103mg (yellow solid), with a yield of 72%.
1H NMR(400MHz,DMSO-d6)δ8.81(s,1H),8.26(s,1H),7.36–7.25(m,5H),6.20(s,2H).13C NMR(100MHz,DMSO-d6)δ166.1,152.7,150.4,146.3,138.3,129.2,129.0,128.2,127.9,48.8.
Figure BDA0002403775650000212
A solution of compound 2ae in EA was prepared, CF (90mg,0.3mmol) was added to the solution of compound 2ae in EA (3mL)3SO2Na (94mg,0.6mmol), Cu (4mg,0.06mmol) and tBuOOH solution (100. mu.L, 0.6mmol) were added dropwise and reacted at 30 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3ae, 26mg (colorless oil) in a yield of 25%.
3ae:Rf＝0.5(DCM:MeOH＝10:1)
1H NMR(400MHz,Chloroform-d)δ9.07(s,1H),8.33(s,1H),7.44–7.34(m,3H),7.07(s,2H),5.68(s,2H).13C NMR(100MHz,Chloroform-d)δ160.9,153.1,149.8,140.5,134.7,134.0,129.7,129.3,126.8,122.0(q,J＝332Hz),50.8.19F NMR(376MHz,Chloroform-d)δ-31.71.
Example 19:
Figure BDA0002403775650000221
to a solution of compound 1af in EtOH (5mL) was added commercial selenourea (98mg,0.8mmol) and the reaction heated to 120 deg.C and stirred at reflux for 3 h. After the reaction was completed by TCL detection, the reaction mixture was filtered, and the precipitate was washed with anhydrous EtOH, and was then dried by spinning to give compound 2af, 172mg (pale green solid) in 74% yield.
1H NMR(400MHz,DMSO-d6)δ8.26(d,J＝3.6Hz,1H),8.24(s,1H),7.35–7.28(m,3H),7.26–7.22(m,2H),5.53(s,2H).13C NMR(100MHz,DMSO-d6)δ177.9,147.8,145.9,138.7,136.9,129.2,128.4,128.1,122.1,51.0.
Figure BDA0002403775650000222
Prepare EA solution of Compound 2af, add CF to EA (3mL) solution of Compound 2af (57mg,0.2mmol)3SO2Na (62mg, 0.4mmol), Cu (3mg,0.04mmol) and tBuOOH solution (70. mu.L, 0.4mmol) were added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the TCL detection reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3af, 46mg (colorless oil) in 65% yield.
3af:Rf＝0.7(Hex:Ethyl Acetate＝2:1)
1H NMR(400MHz,Chloroform-d)δ8.90(s,1H),8.09(s,1H),7.34(dt,J＝21.5,7.3Hz,5H),5.67(s,2H).13C NMR(100MHz,Chloroform-d)δ156.1,154.4,151.5,135.7,132.5,128.9,128.4,128.3,122.4(q,J＝330Hz),116.3,51.4.19F NMR(376MHz,Chloroform-d)δ-30.78.
Example 20:
Figure BDA0002403775650000223
to a solution of compound 1ah in EtOH (5mL) was added commercially available selenourea (68mg,0.55mmol) and the reaction heated to 120 deg.C and stirred at reflux for 2 h. After the reaction was finished by TCL detection, the reaction solution was filtered, and the precipitate was washed with anhydrous EtOH, and then dried by spinning to obtain 2ah, 133mg (pale green solid) with a yield of 99%.
1H NMR(400MHz,DMSO-d6)δ8.55(s,1H),8.24(s,1H),4.74(p,J＝6.8Hz,1H),1.52(d,J＝6.8Hz,6H).13C NMR(100MHz,DMSO-d6)δ174.0,145.6,143.2,142.7,139.6,47.8,22.6.HRMS calcd.For C8H9N4Se-[M-H]-:240.9998.Found:240.9999.
Figure BDA0002403775650000231
A solution of compound 2ah in EA was prepared, and CF (110mg,0.45mmol) was added to a solution of compound 2ah (3mL) in EA3SO2Na (140mg, 0.9mmol), Cu (6mg,0.09mmol), then tBuOOH solution (150. mu.L, 0.9mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3ah, 87mg (colorless oil) in 63% yield.
3ah:Rf＝0.6(Hex:Ethyl Acetate＝2:1)
1H NMR(400MHz,Chloroform-d)δ8.86(s,1H),8.19(s,1H),4.93(p,J＝6.8Hz,1H),1.66(d,J＝6.8Hz,6H).13C NMR(100MHz,Chloroform-d)δ152.5,152.2,149.2,142.3,134.1,122.2(q,J＝330Hz),48.2,22.6.19F NMR(376MHz,Chloroform-d)δ-31.38.HRMS calcd.For C9H10N4F3Se+[M+H]+:311.0017.Found:311.0019.
Example 21:
Figure BDA0002403775650000232
to a solution of compound 1aj in EtOH (5mL) was added commercially available selenourea (123mg,1.0mmol) and the reaction heated to 120 deg.C and stirred at reflux for 2 h. After the reaction was completed by TCL detection, suction filtration was carried out, and the precipitate was washed with anhydrous EtOH and then spin-dried to obtain compound 2aj, 278mg (yellow solid) in a yield of 61%.
1H NMR(400MHz,DMSO-d6)δ8.65(s,1H),8.30(s,1H),6.22(d,J＝5.5Hz,1H),5.89(t,J＝5.7Hz,1H),5.56–5.51(m,1H),4.42–4.36(m,2H),4.26(dd,J＝13.0,6.4Hz,1H),2.11(s,3H),2.03(d,J＝2.5Hz,6H).13C NMR(100MHz,DMSO-d6)δ175.0,170.6,170.0,169.8,146.7,143.2,143.2,140.1,86.2,80.3,72.8,70.4,63.3,21.1,20.9,20.7.HRMS calcd.For C16H17O7N4Se-[M-H]-:457.0268.Found:457.0271.
Figure BDA0002403775650000241
Prepare EA solution of Compound 2aj, add CF to EA (3mL) solution of Compound 2aj (93mg,0.2mmol)3SO2Na (124mg, 0.8mmol), Cu (6mg,0.08mmol), then tBuOOH solution (140. mu.L, 0.8mmol) was added dropwise and reacted at 40 ℃ for 1.0 hour. After the completion of the reaction by TCL detection, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3aj, 61mg (colorless oil) in 62% yield.
3aj:Rf＝0.5(Hex:Ethyl Acetate＝1:1)
1H NMR(400MHz,Chloroform-d)δ8.86(s,1H),8.23(s,1H),6.22(d,J＝5.2Hz,1H),5.94(t,J＝5.3Hz,1H),5.66–5.62(m,1H),4.49–4.41(m,2H),4.37(dd,J＝12.2,4.2Hz,1H),2.15(s,3H),2.11(s,3H),2.08(s,3H).13C NMR(100MHz,Chloroform-d)δ170.4,169.7,169.5,153.6,152.7,149.1,142.9,134.5,122.1(q,J＝330Hz),86.8,80.7,73.2,70.6,63.0,20.9,20.6,20.5.19F NMR(376MHz,Chloroform-d)δ-31.32.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the 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 (6)

1. SCF-containing3Or SeCF3Characterized in that the compound has the following general formula:
Figure FDA0003479774110000011
wherein Y ═ S or Se;
x ═ CH or N;
a ═ C or N;
B＝N；
e ═ C or N;
R1methyl, ethyl, isopropyl, isobutyl, benzyl, ethan-1-ol, cyclopropylmethyl, allyl, propargyl, (2, 2-dimethyltetrahydrofuran [3,4-d ]][1,3]Dioxazol-4-yl) methanol, 2- (acetoxymethyl) tetrahydrofuran-3, 4-diacetic acid diacetate, ethyl 2- ((1H-imidazol-1-yl) methoxy) acetate, 2- ((1H-imidazol-1-yl) methoxy) propane-1, 3-diacetic acid diacetate, and the like alkyl groups;
R2h, cyclohexyl or benzyl;
R3h, an amine or acetamide;
R4me, Et or Bn;
the preparation method comprises the following steps:
(1) dissolving the chloro heterocyclic compound 1 in an EtOH solution, adding 1.0-2.0 times of equivalent of thiourea or selenourea, and then stirring for 1-8 hours at 50-120 ℃ to react to obtain a compound 2;
(2) dissolving the compound 2 in Acetone or EA solution, and adding 2.0-4.0 times of equivalent of CF3SO2Na, 0.2-0.4 equivalent of Cu salt, then dropwise adding 2.0-4.0 equivalent of tBuOOH solution, reacting at 25-40 deg.C for 1.0-2.0 hr to obtain compound 3, i.e. the required SCF-containing3Or SeCF3The heterocyclic compound of (1);
the specific reaction process is as follows:
Figure FDA0003479774110000012
2. the SCF-containing composition of claim 13Or SeCF3Is characterized in that the compound is selected from the compounds with the following structures:
Figure FDA0003479774110000021
3. a composition according to claim 1, comprising a SCF3Or SeCF3The method for producing a heterocyclic compound according to (1), wherein thiourea or selenourea in an amount of 1.5 times the equivalent weight of the chlorinated heterocyclic compound 1 is added at 100 ℃.
4. A composition according to claim 1, comprising a SCF3Or SeCF3The preparation method of the heterocyclic compound is characterized in that in the step (1), after the reaction is finished, the reaction product is directly filtered, the precipitate is washed by anhydrous EtOH, and the precipitate is dried in a spinning mode to obtain the compound 2.
5. A composition according to claim 1, comprising a SCF3Or SeCF3The method for producing a heterocyclic compound of (2), wherein in the step (2), 2.0 equivalent times of CF is added to an Acetone or EA solution of the compound 2 at 40 ℃3SO2Na, 0.2 equivalents of Cu salt, then 2.0 equivalents of tBuOOH solution were added dropwise.
6. The process according to claim 1, wherein in the step (2), after completion of the reaction, the reaction mixture is concentrated under reduced pressure and purified by silica gel column chromatography to obtain compound 3.
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