CN102603750A - Synthesis method of triazolylquinoxalinone derivatives - Google Patents

Synthesis method of triazolylquinoxalinone derivatives Download PDF

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CN102603750A
CN102603750A CN2012100135480A CN201210013548A CN102603750A CN 102603750 A CN102603750 A CN 102603750A CN 2012100135480 A CN2012100135480 A CN 2012100135480A CN 201210013548 A CN201210013548 A CN 201210013548A CN 102603750 A CN102603750 A CN 102603750A
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alkyl
cdcl
nmr
aryl
nan
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蔡倩
丁克
严佳杰
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Guangzhou Institute of Biomedicine and Health of CAS
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Guangzhou Institute of Biomedicine and Health of CAS
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Abstract

The invention discloses a synthesis method of triazolylquinoxalinone derivatives. In an organic solvent environment, by using a cupric salt or cupric salt/ligand combination as a catalyst, a compound disclosed as Formula I reacts with NaN3 in a cascade mode under the conditions of alkali or no alkali to obtain the triazolylquinoxalinone derivatives disclosed as Formula II. The cascade reaction disclosed by the invention can shorten the reaction route, increase the atom economy, avoid using toxic solvent, reduce the waste and enhance the reaction efficiency.

Description

A kind of compound method of triazole quinokysalines derivative
Technical field
The invention belongs to the field of chemical synthesis, be specifically related to the compound method of triazole quinokysalines derivative.
Background technology
Heterogeneous ring compound is the important integral part of organic chemistry, is one type of very important organic cpds, and it has aspect many widely at biochemical industry, daily use chemicals, medicine, material etc. uses; III has sedative-hypnotic effect preferably like the triazole quinokysalines derivative; IV then has (the reference: (1) .J.Med.Chem.2009,52,2587. (2) Eur.J.Med.Chem.2002 of the effect of nicotinic acid appearance vasodilation well; 37; 565. (3) Eur.J.Med.Chem.1998,33,113).The method of traditional synthesizing heterocyclic compounds generally is that multistep is synthetic, inefficiency, and be difficult to introduce different substituted radicals.In recent years, development is new, the method for synthesizing heterocyclic compounds more and more becomes the focus that the organic chemist pays close attention to efficiently.Cascade reaction compound method in modern times upward provides effective means for heterocycle is synthetic, can shorten reaction scheme and improve Atom economy, avoids the use of noxious solvent, reduces waste, improves reaction efficiency.The invention provides a kind of method of utilizing the efficient synthesizing triazazole quinokysalines derivative of cascade reaction.
Figure BDA0000131305780000011
Summary of the invention
The method that the purpose of this invention is to provide a kind of synthesizing triazazole quinokysalines derivative.
Concrete technical scheme is following:
A kind of compound method with triazole quinokysalines derivative of formula II structure, in the environment of organic solvent, mantoquita or mantoquita/ligand combination be as catalyzer, exists or do not have under the situation that alkali exists at alkali, the compound and the NaN that will have formula I structure 3Cascade reaction, synthetic said triazole quinokysalines derivative,
Figure BDA0000131305780000012
Wherein:
R 1=H, CN, NO 2, CF 3, COOR ', carbonyl, C 1～C 12Alkyl, C 1～C 12Aralkyl, aryl, OR ', heterocyclic group;
R 2=aryl, heterocyclic group, C 1～C 12Alkyl, C 1～C 12Aralkyl, C 1～C 12Alkoxyl group;
R 3=H, C 1～C 12Alkyl, C 1～C 12Aralkyl, allyl group, aryl;
X 4＝Cl，Br，I；
R '=C 1～C 12Alkyl.
Preferably, said catalyzer mantoquita is 2% to 50% with respect to the molar percentage of the consumption of the compound of formula I structure, NaN 3With the mol ratio of the compound of said formula I structure be 1: 1 to 2.0: 1, the mol ratio of said part and mantoquita is 1: 1 to 5: 1.
Preferably, wherein
R 1=H, CN, NO 2, CF 3, COOR ', carbonyl, C 1～C 4Alkyl, aryl, OR ';
R 2=aryl, thiophene, C 1～C 4Alkyl, cyclohexyl, C 1～C 4Aralkyl, C 1～C 4Alkoxyl group;
R 3=H, C 1～C 4Alkyl, C 1～C 4Aralkyl, allyl group, aryl;
R '=C 1～C 4Alkyl.
Preferably, said cascade reaction carry out temperature between 40～150 ℃, in 1 hour-48 hours reaction times, the yield of product is that 20-100% does not wait.
Preferably, described alkali is K 2CO 3, Cs 2CO 3, K 3PO 4, NaOH or KOH, described organic solvent are DMSO 99.8MIN., N, dinethylformamide, DMAC N,N, 1,4-dioxane or acetonitrile.
Preferably, described part is the L-proline(Pro), L-4-Ls-hydroxyproline, sarcosine, N; The N-dimethyl glycine hydrochloride, oxine, 2-VPP, 2-minaline, N; N '-dimethyl-ethylenediamine or phenanthroline, said catalyzer mantoquita is CuI, CuBr, CuCl, Cu 2O or CuSO 4
Preferably, said catalyzer mantoquita is CuI.
The reaction expression of above-mentioned reaction is following:
Figure BDA0000131305780000021
Advantage of the present invention is: the invention provides a kind of method of utilizing the efficient synthesizing triazazole quinokysalines derivative of cascade reaction; Cascade reaction compound method in modern times upward provides effective means for heterocycle is synthetic; Can shorten reaction scheme and improve Atom economy; Avoid the use of noxious solvent, reduce waste, improve reaction efficiency.
Embodiment
To help to understand the present invention through following specific embodiment, but not limit content of the present invention.
Embodiment 1
Substrate I (X=I) and NaN 3Reaction (method A)
In the reaction tubes of one one end sealing, add N-(2-iodophenyl)-N-methyl-2-butyne acid amides (1.0mmol), add NaN then 3(1.1mmol), K 2CO 3(2.0mmol), CuI (0.05mmol), 1.0ml DMSO are as solvent, under argon gas or nitrogen protection; In 80 ℃ of following stirring reaction 6h,, there are a large amount of solids to separate out with 10 ml water diluting reaction mixed solutions; Filter, filtrating merges organic phase with 10 milliliters of ethyl acetate extractions twice; Dried faint yellow solid is revolved in the decompression of dry back, and gained solid and filter cake are merged column chromatography (leacheate sherwood oil: ETHYLE ACETATE=10: 1) get product 200mg, productive rate 94%; 1H NMR (CDCl 3, 400MHz) δ 8.50 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.58 (td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42 (m, 2H), 3.70 (s, 3H), 2.80 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.8,130.3, and 129.2,124.1,122.4,116.7,115.6,28.6,11.4; ESI-MS m/z 215.1 [M+H] +.
Embodiment 2
According to of method A, N-(2-iodophenyl)-N-methyl-2-heptyne acid amides (1.0mmol) and NaN 3(1.5mmol), Cs 2CO 3(2.0mmol) in DMA (1mL), 90 ℃ are stirred 6h down.Crude product is through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify, get white solid 235mg, productive rate: 92%; 1H NMR (CDCl 3, 400MHz) δ 8.50 (d, J=7.6Hz, 1H), 7.56 (td, J=8.0Hz, J=1.2Hz, 1H); 7.38-7.42 (m, 2H), 3.70 (s, 3H), 3.19 (t, J=8.0Hz, 2H); 1.78-1.86 (m, 2H), 1.40-1.50 (m, 2H), 0.98 (t, J=4.8Hz, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.7,150.6, and 130.3,129.1,124.0,122.3,122.2,116.7,115.5,31.4,28.6,25.4,22.4,13.8; ESI-MSm/z 257.1 [M+H] +.
Embodiment 3
Figure BDA0000131305780000041
According to of method A, 4-cyclohexyl-N-(2-iodophenyl)-N-methyl-2-butyne acid amides (1.0mmol) and NaN 3(2.0mmol), K 3PO 4(2.0mmol) in DMF, 90 ℃ are stirred 6h down.Crude product through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify yellow solid 255mg, productive rate: 67%; 1H NMR (CDCl 3, 400MHz) δ 8.51 (dd, J=8.8Hz, J=2.0Hz, 1H), 7.56 (td, J=8.0Hz, J=1.6Hz; 1H), 7.38-7.42 (m, 2H), 3.70 (s, 3H), 3.09 (d, J=7.2Hz; 2H), and 1.83-1.93 (m, 1H), 1.61-1.75 (m, 5H), 1.15-1.28 (m, 5H); 13C NMR (CDCl 3, 125MHz) δ 154.7,149.4, and 130.2,129.1,124.0,122.7,122.3,116.7,115.5,38.3,33.0,32.9,28.6,26.4,26.1; ESI-MS m/z 297.2 [M+H] +.
Embodiment 4
Figure BDA0000131305780000042
According to of method A, N-(2-iodophenyl)-N-methyl-2-hexin acid amides (1.0mmol) and NaN 3(1.2mmol), Cu 2O (0.02mmol), NaOH (2.0mmol) are in DMSO, and 90 ℃ are stirred 16h down.Crude product through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify yellow solid 213mg, productive rate: 88%; 1H NMR (CDCl 3, 400MHz) δ 8.51 (d, J=8.0Hz, 1H), 7.56 (td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42 (m, 2H), 3.70 (s, 3H), 3.17 (t, J=8.0Hz, 2H), 1.83-1.90 (m, 2H), 1.03 (t, J=7.2Hz, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.7,130.3, and 129.1,124.0,122.4,116.7,115.5,28.6,27.6,22.7,13.8; ESI-MS m/z 243.3 [M+H] +.
Embodiment 5
Figure BDA0000131305780000051
According to of method A, 4-(benzyloxy)-N-(2-iodo-5-phenyl-phenyl)-N-methyl-2-butyne acid amides (1.0mmol) and NaN 3(1.2mmol), CuSO 4(0.5mmol), in DMSO, 90 ℃ are stirred 16h down.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 334mg, productive rate: 73%; 1H NMR (CDCl 3, 400MHz) δ 8.55 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.59 (td, J=8.0Hz, J=1.2Hz, 1H), 7.41-7.45 (m, 4H), 7.33 (t, J=7.6Hz, 2H), 7.24-7.28 (m, 6H), 5.11 (s, 3H), 4.74 (s, 2H), 3.72 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.0,145.8, and 138.0,130.2,129.5,128.5,128.4,128.3,128.2,128.1,128.0,127.6,124.3,123.6,122.0,116.8,115.6,62.2,28.8; ESI-MS m/z 397.2 [M+H] +.
Embodiment 6
Figure BDA0000131305780000052
According to of method A, N-(2-iodo-5-propionyl group phenyl)-N-methyl-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(1.5mmol), K 2CO 3(2.0mmol), CuI (0.5mmol) is in dioxane (1mL), and 100 ℃ are stirred 48h down.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 66mg, productive rate: 20%; 1H NMR (CDCl 3, 400MHz) δ 8.60 (dd, J=8.4Hz, J=1.6Hz, 1H), 8.36 (d, J=7.2Hz, 2H); 7.61 (td, J=8.0Hz, J=1.6Hz, 1H), 7.50-7.54 (m, 2H), 7.43-7.47 (m, 3H); 3.75 (s, 3H), 2.10 (q, J=7.2Hz, 2H), 1.03 (t, J=7.2Hz, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.3,148.6, and 130.2,129.4,129.3,128.3,124.2,122.2,121.6,116.9,115.5,29.1,20.0,14.2; ESI-MS m/z 333.1 [M+H] +.
Embodiment 7
Figure BDA0000131305780000061
According to of method A, N-(2-iodophenyl)-N-methyl-5-phenyl-valerylene acid amides (1.0mmol) and NaN 3(1.5mmol), Cs 2CO 3(2.0mmol), CuI (0.1mmol), part N, N '-dimethyl-ethylenediamine or phenanthroline (0.2mmol) stir 26h down at 90 ℃.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 279mg, productive rate: 90%; 1H NMR (CDCl 3, 400MHz) δ 8.58 (dd, J=8.8Hz, J=1.6Hz, 1H), 8.25 (d, J=8.0Hz; 2H), 7.59 (td, J=8.0Hz, J=1.2Hz, 1H), 7.41-7.44 (m, 2H); 7.32 (d, J=8.0Hz, 2H), 7.25 (m, 5H), 3.74 (s, 3H); 2.43 (t, J=6.8Hz, 2H), 2.12 (t, J=6.8Hz, 2H); 13C NMR (CDCl 3, 125MHz) δ 154.3,148.8, and 139.4,130.2,129.4,129.2,129.1,128.5,128.3,127.4,127.0,126.4,124.1,122.2,116.9,115.5,29.1,21.4,20.5; ESI-MS m/z 305.1 [M+H] +.
Embodiment 8
Figure BDA0000131305780000062
According to of method A, N-(2-iodophenyl)-3-(2-thienyl)-N-methyl-prop alkynyl amide (1.0mmol) and NaN 3(1.5mmol), CuCl (0.2mmol) in DMSO, 100 ℃ are stirred down 16h.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 266mg, productive rate: 93%; 1H NMR (CDCl 3, 400MHz) δ 8.58 (dd, J=8.4Hz, J=1.6Hz, 1H), 8.35 (d, J=8.8Hz, 2H), 7.59 (td, J=8.4Hz, J=1.6Hz, 1H), 7.26 (m, 1H), 7.04 (d, J=9.2Hz, 1H), 6.99 (d, J=8.8Hz, 1H), 3.74 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 160.5,154.4,148.5,130.7,130.1,129.3,124.1,122.3,121.0,116.8,, 113.8,29.1; ESI-MS m/z 283.0 [M+H] +.
Embodiment 9
Figure BDA0000131305780000071
According to of method A, N-(2-iodo-4-methylbenzene)-N-methyl-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(1.2mmol), CuI (0.05mmol) in DMSO, 90 ℃ are stirred down 15h.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 223mg, productive rate: 77%; 1H NMR (CDCl 3, 400MHz) δ 8.40 (s, 1H), 8.36 (d, J=7.2Hz, 2H), 7.50-7.54 (m, 2H), 7.43-7.47 (m, 1H), 7.39 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.31 (d, J=8.8Hz, 1H), 3.72 (s, 3H), 2.53 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.1,148.5, and 134.6,130.3,129.4,129.3,129.2,128.3,127.9,121.9,121.7,116.9,115.3,29.1,20.9; ESI-MS m/z 291.0 [M+H] +.
Embodiment 10
According to of method A, N-(2-iodo-4-propoxy-benzene)-N-methyl-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(2.0mmol), CuI (0.02mmol) in DMSO, 90 ℃ are stirred down 35h.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 238mg, productive rate: 73%; 1H NMR (CDCl 3, 400MHz) δ 8.36 (d, J=7.2Hz, 2H), 8.07 (d, J=2.8Hz, 1H), 7.52 (t; J=7.2Hz, 2H), 7.45 (t, J=7.2Hz, 1H), 7.36 (d, J=9.2Hz, 1H); 7.16 (dd, J=9.2Hz, J=2.8Hz, 1H), 3.97 (t, J=7.2Hz, 2H); 3.73 (s, 3H), 1.32 (m, 2H), 0.89 (t, J=6.8Hz, 3H); 13C NMR (CDCl 3, 125MHz) δ 156.4,153.8, and 148.6,129.4,129.3,128.3,123.9,122.7,121.9,117.4,116.8,100.3,56.1,29.2,17.3,14.1; ESI-MS m/z 335.1 [M+H] +.
Embodiment 11
Figure BDA0000131305780000073
A is said according to method, N-(2-iodo-4-methylbenzene)-N-methyl-2-butyne acid amides (1.0mmol) and NaN 3(2.0mmol), CuI (0.2mmol) stirs 25h down at 90 ℃.Crude product through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify faint yellow solid 151mg, productive rate: 66%; 1HNMR (CDCl 3, 400MHz) δ 8.31 (s, 1H), 7.35 (dd, J=8.4Hz, J=1.2Hz, 1H), 7.28 (d, J=8.4Hz, 1H), 3.67 (s, 3H), 2.79 (s, 3H), 2.50 (S, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.7,146.0, and 134.4,130.1,128.1,122.7,122.0,116.7,115.4,28.6,20.8,11.4; ESI-MS m/z 229.1 [M+H] +.
Embodiment 12
A is said according to method, N-(2-iodo-4-(trifluoromethyl) benzene)-N-methyl-2-butyne acid amides (1.0mmol) and NaN 3(2.0mmol), CuI (0.1mmol) in DMSO, 60 ℃ are stirred down 36h.Crude product through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify white solid 223mg, productive rate: 79%; 1H NMR (CDCl 3, 400MHz) δ 8.78 (d, J=1.2Hz, 1H), 7.80 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.51 (d, J=8.8Hz, 1H), 3.73 (s, 3H), 2.80 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.6,146.7, and 132.7,126.6,126.3,125.9,125.8,124.4,122.6,122.2,122.1,116.1,114.4,114.3,28.9,11.4; ESI-MS m/z 283.1 [M+H] +.
Embodiment 13
Figure BDA0000131305780000082
A is said according to method, and N-(2-iodo-4-oil of mirbane)-N-methyl-2-butyne acid amides (344mg, 1.0mmol) and NaN 3(98mg, 1.5mmol), CuI (0.1mmol) in DMSO, 40 ℃ are stirred down 33h.Crude product through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify yellow solid 110mg, productive rate: 42%; 1H NMR (CDCl 3, 400MHz) δ 9.37 (d, J=2.4Hz, 1H), 8.43 (dd, J=9.2Hz, J=2.4Hz, 1H), 7.53 (d, J=9.2Hz, 1H), 3.76 (s, 3H), 2.81 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.4,147.2, and 143.3,134.8,124.1,122.4,122.0,116.1,112.8,58.5,53.4,29.2,18.4,11.3; ESI-MS m/z 260.1 [M+H] +.
Embodiment 14
Figure BDA0000131305780000083
A is said according to method, N-(4-cyanic acid-2-iodobenzene)-N-methyl-2-butyne acid amides (1.0mmol) and NaN 3(1.5mmol), K 2CO 3(2.0mmol), CuI (0.1mmol) is in DMSO, and 90 ℃ are stirred 3h down.Crude product through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify white solid 189mg, productive rate: 79%; 1H NMR (CDCl 3, 400MHz) δ 8.79 (d, J=1.6Hz, 1H), 7.82 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.49 (d, J=8.8Hz, 1H), 3.72 (s, 3H), 2.80 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.4,147.0, and 133.5,132.4,122.4,120.5,117.2,116.5,107.7,58.5,28.9,18.4,11.3; ESI-MS m/z 240.1 [M+H] +.
Embodiment 15
Figure BDA0000131305780000091
A is said according to method, N-(2-iodophenyl)-N-methyl-2-butyne acid amides (1.0mmol) and NaN 3(1.5mmol), K 2CO 3(2.0mmol), CuI (0.2mmol) is in DMSO, and 120 ℃ are stirred 46h down.Crude product through column chromatography (10: 1 sherwood oils: ETHYLE ACETATE) purify white solid 42mg, productive rate: 22%; 1H NMR (CDCl 3, 400MHz) δ 8.80 (br, 1H), 8.50 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.58 (td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42 (m, 2H), 2.80 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.8,130.3, and 129.2,124.1,122.4,116.7,115.6,11.4; ESI-MS m/z 201.1 [M+H] +.
Embodiment 16
Figure BDA0000131305780000092
According to of method A, N-(2-iodophenyl)-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(1.5mmol), CuI (0.2mmol) in DMSO, 120 ℃ are stirred down 46h.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 56mg, productive rate: 20%; 1H NMR (CDCl 3, 400MHz) δ 8.80 (br, 1H), 8.60 (dd, J=8.4Hz, J=1.6Hz, 1H), 8.36 (d, J=7.2Hz, 2H), 7.61 (td, J=8.0Hz, J=1.6Hz, 1H), 7.50-7.54 (m, 2H), 7.43-7.47 (m, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.3,148.6, and 130.2,129.4,129.3,128.3,124.2,122.2,121.6,116.9,115.5; ESI-MS m/z 263.1 [M+H] +.
Embodiment 17
Figure BDA0000131305780000101
According to of method A, N-(2-iodophenyl)-3-phenyl-N-propyl group propine acid amides (1.0mmol) and NaN 3(1.2mmol), CuI (0.1mmol) in DMSO, 90 ℃ are stirred down 8h.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 264mg, productive rate: 87%; 1H NMR (CDCl 3, 400MHz) δ 8.61 (dd, J=8.4Hz, J=1.2Hz, 1H), 8.37 (d, J=7.2Hz, 2H); 7.58 (td, J=8.4Hz, J=1.6Hz, 1H), 7.50-7.54 (m, 2H), 7.40-7.47 (m, 3H); 4.26 (t, J=8.0Hz, 2H), 1.79-1.88 (m, 2H), 1.09 (t, J=7.6Hz, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.1,148.5, and 129.4,129.3,128.3,124.0,122.3,121.6,117.1,115.5,43.8,20.7,11.3; ESI-MS m/z 305.2 [M+H] +.
Embodiment 18
Figure BDA0000131305780000102
According to of method A, N-benzyl-N-(2-iodophenyl)-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(1.2mmol), CuI (0.1mmol) in DMSO, 90 ℃ are stirred down 8h.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 327mg, productive rate: 93%; 1H NMR (CDCl 3, 400MHz) δ 8.61 (d, J=8.0Hz, 1H), 8.41 (d, J=7.2Hz, 2H), 7.53 (t, J=7.2Hz, 2H), 7.46 (t, J=7.2Hz, 2H), 7.40 (d, J=7.6Hz, 1H), 7.28-7.37 (m, 6H), 5.57 (s, 2H); 13C NMR (CDCl 3, 125MHz) δ 154.6,149.0, and 135.2,129.5,129.4,129.2,129.0,128.4,127.8,126.6,124.3,122.3,121.5,117.0,116.4,58.5,45.8,18.4; ESI-MS m/z353.1 [M+H] +.
Embodiment 19
Figure BDA0000131305780000103
According to of method A, N-allyl group-N-(2-iodophenyl)-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(1.2mmol), K 2CO 3(2.0mmol), CuI (0.1mmol) is in MeCN, and 90 ℃ are stirred 38h down.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 284mg, productive rate: 94%; 1H NMR (CDCl 3, 400MHz) δ 8.61 (dd, J=8.0Hz, J=1.2Hz, 1H), 8.38 (d, J=1.6Hz; 2H), 7.55 (td, J=8.4Hz, J=1.6Hz, 1H), 7.50-7.52 (m, 2H); 7.40-7.47 (m, 3H), 5.93-6.03 (m, 1H), 5.31 (d, J=10.0Hz; 1H), 5.25 (d, J=17.2Hz, 1H), 4.96-4.97 (m, 2H); 13C NMR (CDCl 3, 125MHz) δ 154.0,148.8, and 130.8,129.4,129.3,129.2,128.3,124.2,122.3,121.5,118.1,117.0,116.1,44.4; ESI-MS m/z 303.2 [M+H] +.
Embodiment 20
Figure BDA0000131305780000111
According to of method A, 4-(benzyloxy)-N-(2-iodophenyl)-N-methyl-2-butyne acid amides (1.0mmol) and NaN 3(1.2mmol), K 2CO 3(2.0mmol), CuI (0.05mmol), part 2-VPP or 2-minaline (0.1mmol) are in DMSO (1mL), and 90 ℃ are stirred 6h down.Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 234mg, productive rate: 73%; 1H NMR (CDCl 3, 400MHz) δ 8.55 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.59 (td, J=8.0Hz, J=1.2Hz, 1H), 7.41-7.45 (m, 4H), 7.33 (t, J=7.6Hz, 2H), 7.24-7.28 (m, 1H), 5.11 (s, 3H), 4.74 (s, 2H), 3.72 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.0,145.8, and 138.0,130.2,129.5,128.3,128.0,127.6,124.3,123.6,122.0,116.8,115.6,62.2,28.8; ESI-MS m/z 321.0 [M+H] +.
Embodiment 21
Figure BDA0000131305780000112
According to of method A, N-(2-iodo-4-anisole)-N-methyl-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(2.0mmol), K 3PO 4(2.0mmol), CuBr (0.15mmol), part N, N-dimethyl glycine hydrochloride or oxine (0.5mmol) 40 ℃ of stirring 40h in DMSO (1mL).Crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 223mg, productive rate: 73%; 1H NMR (CDCl 3, 400MHz) δ 8.36 (d, J=7.2Hz, 2H), 8.07 (d, J=2.8Hz, 1H), 7.52 (t; J=7.2Hz, 2H), 7.45 (t, J=7.2Hz, 1H), 7.36 (d, J=9.2Hz, 1H); 7.16 (dd, J=9.2Hz, J=2.8Hz, 1H), 3.97 (s, 3H), 3.73 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 156.4,153.8, and 148.6,129.4,129.3,128.3,123.9,122.7,121.9,117.4,116.8,100.3,56.1,29.2; ESI-MS m/z 307.1 [M+H] +.
Embodiment 22
Substrate I (X=Br) and NaN 3Reaction (method B)
In the reaction tubes of one one end sealing, add N-(2-bromophenyl)-N-methyl-2-butyne acid amides (1.0mmol), add NaN then 3(1.1mmol), CuI (0.15mmol), 1.0ml DMSO are as solvent, under argon gas or nitrogen protection; In 90 ℃ of stirring reaction 20h,, there are a large amount of solids to separate out with 10 ml water diluting reaction mixed solutions; Filter, filtrating merges organic phase with 10 milliliters of ethyl acetate extractions twice; Dried faint yellow solid is revolved in the decompression of dry back, and gained solid and filter cake are merged column chromatography (leacheate sherwood oil: ETHYLE ACETATE=10: 1) get product 188mg, productive rate 88%; 1H NMR (CDCl 3, 400MHz) δ 8.50 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.58 (td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42 (m, 2H), 3.70 (s, 3H), 2.80 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.8,130.3, and 129.2,124.1,122.4,116.7,115.6,28.6,11.4; ESI-MS m/z 215.1 [M+H] +.
Embodiment 23
Figure BDA0000131305780000122
In the reaction tubes of one one end sealing, add N-(2-bromine 4-methoxycarbonyl phenyl)-N-methyl-2-butyne acid amides (1.0mmol), add NaN then 3(1.1mmol), CuI (0.15mmol), 1.0ml DMSO are as solvent, under argon gas or nitrogen protection; In 90 ℃ of stirring reaction 20h,, there are a large amount of solids to separate out with 10 ml water diluting reaction mixed solutions; Filter, filtrating merges organic phase with 10 milliliters of ethyl acetate extractions twice; Dried faint yellow solid is revolved in the decompression of dry back, and gained solid and filter cake are merged column chromatography (leacheate sherwood oil: ETHYLE ACETATE=10: 1) get product 246mg, productive rate 90%; 1H NMR (CDCl 3, 400MHz) δ 8.50 (s, 1H), 7.78 (d, J=8.0Hz, 1H), 7.39 (d, J=8.0Hz, 1H), 4.12 (s, 3H), 3.77 (s, 3H), 2.83 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 167.4,154.8, and 135.3,133.2,127.1,125.4,118.7,117.6,61.2,30.6,12.4; ESI-MS m/z 273.1 [M+H] +.
Embodiment 24
Figure BDA0000131305780000131
According to of method B, N-(2-bromophenyl)-N-methyl-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(1.1mmol) CuI (0.15mmol), 1.0ml DMF be as solvent, under argon gas or nitrogen protection, in 90 ℃ of stirring reaction 20h, crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 224mg, productive rate: 81%; 1H NMR (CDCl 3, 400MHz) δ 8.60 (dd, J=8.4Hz, J=1.6Hz, 1H), 8.36 (d, J=7.2Hz, 2H), 7.61 (td, J=8.0Hz, J=1.6Hz, 1H), 7.50-7.54 (m, 2H), 7.43-7.47 (m, 3H), 3.75 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.3,148.6, and 130.2,129.4,129.3,128.3,124.2,122.2,121.6,116.9,115.5,29.1; ESI-MS m/z 277.1 [M+H] +.
Embodiment 25
Figure BDA0000131305780000132
According to of method B, N-(2-bromophenyl)-N-methyl-2-hexin acid amides (1.0mmol) and NaN 3(1.5mmol), CuI (0.05mmol) in DMSO (1mL), 90 ℃ of stirring reaction 20h, crude product through column chromatography (3: 1 methylene dichloride: sherwood oil) purify white solid 211mg, productive rate: 87%; 1H NMR (CDCl 3, 400MHz) δ 8.51 (d, J=8.0Hz, 1H), 7.56 (td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42 (m, 2H), 3.70 (s, 3H), 3.17 (t, J=8.0Hz, 2H), 1.83-1.90 (m, 2H), 1.03 (t, J=7.2Hz, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.7,130.3, and 129.1,124.0,122.4,116.7,115.5,28.6,27.6,22.7,13.8; ESI-MS m/z 243.3 [M+H] +.
Embodiment 26
Substrate I (X=Cl) and NaN 3Reaction (method C)
Figure BDA0000131305780000141
In the reaction tubes of one one end sealing, add N-(2-chloro-phenyl-)-N-methyl-2-butyne acid amides (1.0mmol), add NaN then 3(1.5mmol), K 2CO 3(2mmol), L-proline(Pro) (0.2mmol), CuI (0.1mmol), 1.0ml DMF is as solvent; Under argon gas or nitrogen protection,,, there are a large amount of solids to separate out with 10 ml water diluting reaction mixed solutions in 110 ℃ of stirring reaction 10h; Filter, filtrating merges organic phase with 10 milliliters of ethyl acetate extractions twice; Dried faint yellow solid is revolved in the decompression of dry back, and gained solid and filter cake are merged column chromatography (leacheate sherwood oil: ETHYLE ACETATE=10: 1) get product 154mg, productive rate 72%; 1H NMR (CDCl 3, 400MHz) δ 8.50 (dd, J=8.8Hz, J=1.6Hz, 1H), 7.58 (td, J=8.0Hz, J=1.2Hz, 1H), 7.39-7.42 (m, 2H), 3.70 (s, 3H), 2.80 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.8,130.3, and 129.2,124.1,122.4,116.7,115.6,28.6,11.4; ESI-MS m/z 215.1 [M+H] +.
Embodiment 27
Figure BDA0000131305780000142
According to of method C, N-(2-chloro-phenyl-)-N-methyl-3-phenyl-allylene acid amides (1.0mmol) and NaN 3(1.5mmol), CuSO 4(0.5mmol), ligand L-proline(Pro) or 4-Ls-hydroxyproline (1mmol) 110 ℃ of stirring reaction 10h in DMSO (1mL) get yellow solid 168mg productive rate: 61%; 1H NMR (CDCl 3, 400MHz) δ 8.60 (dd, J=8.4Hz, J=1.6Hz, 1H), 8.36 (d, J=7.2Hz, 2H), 7.61 (td, J=8.0Hz, J=1.6Hz, 1H), 7.50-7.54 (m, 2H), 7.43-7.47 (m, 3H), 3.75 (s, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.3,148.6, and 130.2,129.4,129.3,128.3,124.2,122.2,121.6,116.9,115.5,29.1; ESI-MS m/z 277.1 [M+H] +.
Embodiment 28
Figure BDA0000131305780000143
C is said according to method, N-(2-iodophenyl)-N-methyl-2-heptyne acid amides (1.0mmol) and NaN 3(1.5mmol), CuI (0.2mmol), L-proline(Pro) (0.4mmol) 150 ℃ of stirring reaction 10h in DMF (1mL) are getting yellow solid 148mg productive rate: 58%; 1H NMR (CDCl 3, 400MHz) δ 8.50 (d, J=7.6Hz, 1H), 7.56 (td, J=8.0Hz, J=1.2Hz, 1H); 7.38-7.42 (m, 2H), 3.70 (s, 3H), 3.19 (t, J=8.0Hz, 2H); 1.78-1.86 (m, 2H), 1.40-1.50 (m, 2H), 0.98 (t, J=4.8Hz, 3H); 13C NMR (CDCl 3, 125MHz) δ 154.7,150.6, and 130.3,129.1,124.0,122.3,122.2,116.7,115.5,31.4,28.6,25.4,22.4,13.8; ESI-MS m/z 257.1 [M+H] +

Claims (7)

1. compound method with triazole quinokysalines derivative of formula II structure; It is characterized in that in the environment of organic solvent, mantoquita or mantoquita and ligand combination are as catalyzer; Exist or do not have under the situation that alkali exists at alkali, the compound and the NaN that will have formula I structure 3Cascade reaction, synthetic triazole quinokysalines derivative with formula II structure,
Figure FDA0000131305770000011
Wherein:
R 1=H, CN, NO 2, CF 3, COOR ', carbonyl, C 1～C 12Alkyl, C 1～C 12Aralkyl, aryl, OR ', heterocyclic group;
R 2=aryl, heterocyclic group, C 1～C 12Alkyl, naphthenic base, C 1～C 12Aralkyl, C 1～C 12Alkoxyl group;
R 3=H, C 1～C 12Alkyl, C 1～C 12Aralkyl, allyl group, aryl;
X 4＝Cl，Br，I；
R '=C 1～C 12Alkyl.
2. compound method according to claim 1 is characterized in that, said catalyzer mantoquita is 2%-50% with respect to the molar percentage of the consumption of the compound of formula I structure, NaN 3With the mol ratio of the compound of said formula I structure be 1-2: 1, the mol ratio of said part and mantoquita is 1-5: 1.
3. compound method according to claim 1 is characterized in that, wherein
R 1=H, CN, NO 2, CF 3, COOR ', carbonyl, C 1～C 4Alkyl, aryl, OR ';
R 2=aryl, thiophene, C 1～C 4Alkyl, cyclohexyl, C 1～C 4Aralkyl, C 1～C 4Alkoxyl group;
R 3=H, C 1～C 4Alkyl, C 1～C 4Aralkyl, allyl group, aryl;
R '=C 1～C 4Alkyl.
4. compound method according to claim 1 is characterized in that, said cascade reaction carry out temperature between 40～150 ℃, 1 hour-48 hours reaction times.
5. according to each described compound method of claim 1-4, it is characterized in that described alkali is K 2CO 3, Cs 2CO 3, K 3PO 4, NaOH or KOH, described organic solvent are DMSO 99.8MIN., N, dinethylformamide, DMAC N,N, 1,4-dioxane or acetonitrile.
6. according to each described compound method of claim 1-4, it is characterized in that described part is the L-proline(Pro), the L-4-Ls-hydroxyproline; Sarcosine, N, N-dimethyl glycine hydrochloride, oxine; The 2-VPP, 2-minaline, N, N '-dimethyl-ethylenediamine or phenanthroline; Said catalyzer mantoquita is CuI, CuBr, CuCl, Cu 2O or CuSO 4
7. compound method according to claim 6 is characterized in that, said catalyzer mantoquita is CuI.
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JP2016124812A (en) * 2014-12-26 2016-07-11 株式会社ヤクルト本社 Compound having znf143 inhibitory activity and use thereof
CN107602570A (en) * 2017-10-24 2018-01-19 暨南大学 A kind of nitrogenous polynary and heterocyclic compound method of synthesis
CN114195792A (en) * 2021-12-03 2022-03-18 常州大学 Synthesis method of 1,2, 3-triazole quinoxalinone derivative
CN115321495A (en) * 2022-07-28 2022-11-11 东北石油大学 Metal nitrogen-rich compound FeN 8 Method of synthesis of
CN115321495B (en) * 2022-07-28 2023-07-21 东北石油大学 Metal nitrogen-rich compound FeN 8 Is synthesized by the method of (2)

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