CN109232592A - A kind of synthetic method of benzofuran [2,3-b] pyrazines derivatives - Google Patents
A kind of synthetic method of benzofuran [2,3-b] pyrazines derivatives Download PDFInfo
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- CN109232592A CN109232592A CN201811128003.8A CN201811128003A CN109232592A CN 109232592 A CN109232592 A CN 109232592A CN 201811128003 A CN201811128003 A CN 201811128003A CN 109232592 A CN109232592 A CN 109232592A
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- benzofuran
- pyrazines derivatives
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- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 150000003216 pyrazines Chemical class 0.000 title claims description 29
- 238000010189 synthetic method Methods 0.000 title claims description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 13
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000012544 monitoring process Methods 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000000377 silicon dioxide Substances 0.000 claims description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- CXNIUSPIQKWYAI-UHFFFAOYSA-N 4,5-bis(diphenylphosphino)-9,9-dimethyl-xanthene Substances C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- 235000011009 potassium phosphates Nutrition 0.000 claims description 7
- 238000007789 sealing Methods 0.000 claims description 7
- 239000007832 Na2SO4 Substances 0.000 claims description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 6
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 6
- RIWNFZUWWRVGEU-UHFFFAOYSA-N isocyanomethylbenzene Chemical compound [C-]#[N+]CC1=CC=CC=C1 RIWNFZUWWRVGEU-UHFFFAOYSA-N 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 239000001103 potassium chloride Substances 0.000 claims description 4
- 235000011164 potassium chloride Nutrition 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 235000011056 potassium acetate Nutrition 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 238000004458 analytical method Methods 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 18
- 229910052763 palladium Inorganic materials 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 5
- -1 3-b]pyrazine compound Chemical class 0.000 abstract description 4
- 238000001914 filtration Methods 0.000 abstract description 4
- BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical class C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 238000001035 drying Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 abstract 1
- 238000010898 silica gel chromatography Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- HBRAWQBSCCABMZ-UHFFFAOYSA-N 2,3-diphenyl-[1]benzothiolo[2,3-b]pyrazine Chemical class C1(=CC=CC=C1)C=1N=C2C(=NC=1C1=CC=CC=C1)SC1=C2C=CC=C1 HBRAWQBSCCABMZ-UHFFFAOYSA-N 0.000 description 1
- GJMIILRZDPIQPL-UHFFFAOYSA-N 2,3-dipropyl-1-benzofuran Chemical compound C1=CC=C2C(CCC)=C(CCC)OC2=C1 GJMIILRZDPIQPL-UHFFFAOYSA-N 0.000 description 1
- HUGNLEZLTOVJLD-UHFFFAOYSA-N 2-bromo-3-methylphenol Chemical class CC1=CC=CC(O)=C1Br HUGNLEZLTOVJLD-UHFFFAOYSA-N 0.000 description 1
- YUQUNWNSQDULTI-UHFFFAOYSA-N 2-bromobenzenethiol Chemical compound SC1=CC=CC=C1Br YUQUNWNSQDULTI-UHFFFAOYSA-N 0.000 description 1
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- MESJRHHDBDCQTH-UHFFFAOYSA-N 3-(dimethylamino)phenol Chemical compound CN(C)C1=CC=CC(O)=C1 MESJRHHDBDCQTH-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
本发明公开了一种苯并呋喃[2,3‑b]吡嗪衍生物的合成方法，以邻卤素苯酚与苄异腈为原料，在封管中先加入0.2mmol的邻卤素苯酚和0.3mmol的苄异腈，再加入2mol%的钯催化剂，2‑3倍量的钾盐及1毫升溶剂，在100‑150℃下反应6~12h，TLC监测反应；待反应完全后，冷却到室温，过滤，最后用无水Na2SO4干燥，产物减压除去溶剂，剩余物经快速硅胶柱析层纯化得到苯并呋喃[2,3‑b]吡嗪化合物产物。在该反应中，钯催化剂显示了高催化活性和可回收性。该方法操作简单，原料易得，反应步骤少，产量高，应用前景广泛，适合于工业化生产。
The invention discloses a method for synthesizing a benzofuran[2,3-b]pyrazine derivative. Using o-halogen phenol and benzisonitrile as raw materials, 0.2 mmol of o-halogen phenol and 0.3 mmol of o-halogen phenol and 0.3 mmol of o-halogen phenol are firstly added in a sealed tube. 2 mol% palladium catalyst, 2-3 times the amount of potassium salt and 1 ml of solvent, react at 100-150 ℃ for 6-12 h, TLC monitoring the reaction; after the reaction is complete, cool to room temperature, Filtration, and finally drying with anhydrous Na 2 SO 4 , the solvent was removed from the product under reduced pressure, and the residue was purified by flash silica gel column chromatography to obtain the benzofuran[2,3-b]pyrazine compound product. In this reaction, the palladium catalyst showed high catalytic activity and recyclability. The method has the advantages of simple operation, readily available raw materials, few reaction steps, high yield and wide application prospect, and is suitable for industrial production.
Description
Technical field
The present invention relates to the synthetic method of pyrazines derivatives, specifically a kind of benzofuran [2,3-b] pyrazines derivatives
Synthetic method.
Background technique
Benzofuran [2,3-b] pyrazine is a kind of compound with significant pharmacological activity.Benzofuran [3,2-d] is derivative
Object is found to be effective 4 regulator of histamine H (2006050965,2006.).Benzofuran [3,2-d] pyrimidine derivatives are more
The novel inhibitors of target spot tyrosine kinase, be currently under in Phase I clinical trial (Eur. J. Med. Chem. 2006,41,
367-372).However, also seldom about the synthetic method of benzofuran [2,3-b] pyrazines derivatives and the research of pharmacological activity.
In the past few decades, the synthetic method about benzofuran [2,3-b] pyrazines derivatives is seldom, and there are mainly two types of:
(1) salicylideoHydride is added with sodium deprotonation in methyloxime in anhydrous tetrahydro furan, then uses methyl sulphonyl -1 3-,
The processing of 2,4- triazines, obtains intermediate product, finally its solution is flowed back in nitrobenzene, slowly consume during 3 days,
Available 8% benzofuran [2,3-b] pyrazines derivatives (Tetrahedron, 1987,43,5159-5168).(2) by 2,
Chloro- 5, the 6- dicyano pyrazine of 3- bis-, which is dissolved in 50 mL toluene, to be heated, and the toluene that 3- Dimethylaminophenol is then added dropwise is molten
Liquid, mixture flow back 24 hours, finally obtain product (Organic Reaction, 1998,53).And existing synthesis benzo
The method of furans [2,3-b] pyrazines derivatives needs the pre- function dough of multi-step or starting material.Benzofuran [2,3- at present
B] pyrazines derivatives synthetic method and pharmacological activity research it is also seldom.Therefore, synthesis benzene is obtained from raw material simple and easy to get
And the simple and effective method of furans [2,3-b] pyrazines derivatives, it is significantly to work, and the research to its pharmacological activity
It is in demand.
Summary of the invention
The object of the present invention is to provide a kind of new synthetic methods of benzofuran [2,3-b] pyrazines derivatives, with adjacent halogen
Phenol and benzyl isonitrile are raw material, under palladium catalyst effect, have synthesized benzofuran [2,3-b] pyrazines derivatives.
Realizing the technical solution of the object of the invention is:
A kind of synthetic method of benzofuran [2,3-b] pyrazines derivatives, synthetic method general formula are as follows:
R1 =H, aromatic radical, fat-based；
R2 =fat-based, aromatic radical；
Wherein, Pd catalyst are as follows: palladium nanometer polymer Pd NPs/POL-xantphos；
Sylvite are as follows: potassium carbonate, potassium phosphate, potassium acetate etc.；
Solvent are as follows: N,N-dimethylformamide, 1,2- dichloroethanes, 1,4- dioxane, acetonitrile, toluene etc..
The universal synthesis method of benzofuran [2,3-b] pyrazines derivatives is:
(1) the adjacent halogen phenol of 0.2 mmol and the benzyl isonitrile of 0.3 mmol are first added in tube sealing, the Pd for adding 2 mol% is urged
Agent, the 2-3 times of sylvite (potassium carbonate, potassium phosphate, potassium acetate etc.) measured and 1 milliliter of solvent (n,N-Dimethylformamide, 1,2-
Dichloroethanes, Isosorbide-5-Nitrae-dioxane, acetonitrile, toluene etc.), 6 ~ 12 h, TLC monitoring reaction are reacted at 100-150 DEG C；
(2) after complete reaction, it is cooled to room temperature, filters, finally uses anhydrous Na2SO4Dry, product at reduced pressure removes solvent, remains
Excess purifies to obtain benzofuran [2,3-b] pyrazines derivatives through Flash silica column analysis layer.
The Flash silica column chromatographic purifying, eluant, eluent is ethyl acetate: petroleum ether=1:100-200.
The structural formula of benzofuran [2,3-b] pyrazines derivatives that the present invention synthesizes is as follows:
。
Nitrogen-containing heterocycle compound plays an important role in modern organic chemistry, they have biological significance in many
Natural products, drug and material science application in be widely present (Chem. Rev. 2012,112,3611-3640).
In numerous nitrogenous polycyclic compounds, benzofuran [2,3-b] pyrazines derivatives are drug candidate and bioactive compound
In common structural unit.
The present invention provides a kind of new synthetic methods of benzofuran [2,3-b] pyrazines derivatives, and in the reaction, palladium is urged
Agent shows high catalytic activity and recuperability.This method is easy to operate, and raw material is easy to get, and reaction step is few, and yield is high, application
Prospect is extensive, is suitable for industrialized production.
Detailed description of the invention
Fig. 1 is synthetic method general formula of the present invention.
Specific embodiment
The synthesis of five kinds of benzofuran [2,3-b] pyrazines derivatives with reference to the accompanying drawings and examples and Characterization of The Products pair
The content of present invention is further described, but is not limitation of the invention.
Embodiment 1
The synthesis of 2,3- diphenylisobenzofuran [2,3-b] pyrazines derivatives:
Referring to Fig.1,0.2 mmol(0.034 mg is added in tube sealing) o-bromophenol and 0.3 mmol(37 μ L) benzyl it is different
Nitrile adds 2 mol% Pd NPs/POL-xantphos catalyst (15 mg), the potassium carbonate (0.0637 mg) and 1 of 2 times of amounts
The n,N-Dimethylformamide of milliliter, flow back 8 h at 130 DEG C, TLC monitoring reaction；After complete reaction, it is cooled to room temperature
Afterwards, it filters, finally uses anhydrous Na2SO4Dry, product at reduced pressure removes solvent, and residue is through Flash silica column chromatographic purifying (acetic acid
Ethyl ester: petroleum ether=1:120) obtain 82.2 mg of yellow solid 1a, yield 85%(mp 208 ~ 210oC)；
1H NMR (400 MHz, CDCl3) δ8.29 (d, 1H), 7.70 - 7.61 (m, 2H ), 7.53 - 7.46
(m, 5H), 7.37 - 7.30 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 156.90, 155.95,
149.63, 148.67, 139.17, 138.46, 135.53, 130.38, 130.14, 130.03, 128.55,
128.29, 128.25, 128.12, 124.21, 122.10, 121.73, 112.61, 77.32, 77.00, 76.68;
HRES (m/z) (ESI): calcd for C22H15N2O [M+H]+ 323.1184, found 323.1184。
Embodiment 2
The synthesis of 9- methyl -2,3- diphenylisobenzofuran [2,3-b] pyrazines derivatives:
Referring to Fig.1,0.2 mmol(0.037 mg is added in tube sealing) 2 bromo- 3- methylphenols and 0.3 mmol(37 μ L)
Benzyl isonitrile, 2 mol% Pd NPs/POL-xantphos(15 mg), 2.1 times amount potassium phosphates (0.0669 mg) and 1 milliliter
1,2- dichloroethanes, flow back 8 h at 100 DEG C, TLC monitoring reaction；After complete reaction, after being cooled to room temperature, filtering,
Finally use anhydrous Na2SO4Dry, product at reduced pressure removes solvent, and residue is through Flash silica column chromatographic purifying (ethyl acetate: petroleum
Ether=1:150) obtain 79.7 mg of yellow solid 2a, yield 79%(mp 181 ~ 183oC)；
1H NMR (400 MHz, CDCl3) δ 7.52 - 7.46 (m, 6H), 7.31 - 7.27 (m, 6H), 7.22
(S, 1H), 2.95 (S, 3H); 13C NMR (101 MHz, CDCl3) δ 157.01, 155.73, 149.17,
149.10, 147.63, 139.43, 138.82, 136.92, 136.29, 130.24, 130.17, 130.03,
128.48, 128.19, 128.15, 125.25, 120.39, 109.67, 77.32, 77.00, 76.68, 18.77;
HRES (m/z) (ESI): calcd forC23H17N2O [M+H]+ 337.1341, found 337.1330。
Embodiment 3
2,3- diphenyl -8-(trifluoromethyl) benzofuran simultaneously [2,3-b] pyrazines derivatives synthesis:
Referring to Fig.1,0.2 mmol(0.048 mg is added in tube sealing) the bromo- 4-(trifluoromethyl of 2-) phenol and 0.3 mmol
The benzyl isonitrile of (37 μ L), 2 mol% Pd NPs/POL-xantphos(15 mg), the potassium phosphate (0.0732 mg) of 2.3 times of amounts
And 1 milliliter of Isosorbide-5-Nitrae-dioxane, flow back 8 h at 140 DEG C, TLC monitoring reaction；After complete reaction, it is cooled to room temperature
Afterwards, it filters, finally uses anhydrous Na2SO4Dry, product at reduced pressure removes solvent, and residue is through Flash silica column chromatographic purifying (acetic acid
Ethyl ester: petroleum ether=1:130) obtain 83.1 mg of yellow solid 3a, yield 71%(mp 144 ~ 145oC)；
1H NMR (500 MHz, CDCl3) δ 8.61 (s, 1H), 7.91 (d, 1H), 7.81 (d, 1H), 7.52
– 7.49 (m, 4H), 7.37 – 7.33 (m, 6H); 13C NMR (126 MHz, CDCl3) δ 158.08,
156.55, 150.67, 150.03, 138.78, 138.12, 134.48, 130.16, 129.98, 128.95,
128.57, 128.42, 128.27, 127.21, 126.92, 125.11, 122.95, 122.57, 122.20,
119.91, 113.29, 77.25, 77.00, 76.75; HRES (m/z) (ESI): calcd for C23H14F3N2O [M
+H]+ 391.1098, found 391.1051。
Embodiment 4
The synthesis of 2,3- diphenyl benzo [4,5] thieno [2,3-b] pyrazines derivatives:
Referring to Fig.1,0.2 mmol(0.038 mg is added in tube sealing) 2- bromo thiophenol and 0.3 mmol(37 μ L) benzyl it is different
Nitrile, 2 mol% Pd NPs/POL-xantphos(15 mg), the potassium phosphate (0.070mg) and 1 milliliter of acetonitrile of 2.2 times of amounts,
Flow back 8 h at 150 DEG C, TLC monitoring reaction；After complete reaction, after being cooled to room temperature, anhydrous Na is finally used in filtering2SO4
Dry, product at reduced pressure removes solvent, and residue obtains yellow through Flash silica column chromatographic purifying (ethyl acetate: petroleum ether=1:140)
Color solid 4a 22.3 mg, yield 22%(mp 290 ~ 291oC)；
1H NMR (400 MHz, CDCl3) δ 8.54 (d, 1H), 7.90 (d, 1H), 7.63 - 7.51 (m,
6H), 7.35 (t, 6H); 13C NMR (101 MHz, CDCl3) δ 154.47, 150.70, 149.69, 144.64,
139.40, 139.03, 138.86, 131.93, 130.09, 129.96, 129.33, 128.60, 128.47,
128.25, 125.44, 123.73, 123.33, 77.32, 77.00, 76.68; HRES (m/z) (ESI): calcd
forC22H15N2S [M+H]+ 339.0956, found 339.0950。
Embodiment 5
The synthesis of 2,3- dipropyl benzofuran [2,3-b] pyrazines derivatives:
Referring to Fig.1,0.2 mmol(0.026 mg is added in tube sealing) o-chlorphenol and 0.3 mmol(32 μ L) normal-butyl
Isonitrile, 2 mol% Pd NPs/POL-xantphos(15 mg), the potassium phosphate (0.079mg) and 1 milliliter of first of 2.5 times of amounts
Benzene, flow back 8 h at 120 DEG C, TLC monitoring reaction；After complete reaction, after being cooled to room temperature, filtering, finally with anhydrous
Na2SO4Dry, product at reduced pressure removes solvent, residue through Flash silica column chromatographic purifying (ethyl acetate: petroleum ether=1:
180) yellow oily 5a 27.4mg, yield 36% are obtained；
1H NMR(400 MHz, CDCl3) δ 8.18 (s, 1H), 7.61 - 7.52 (m, 2H), 7.41 (t, 1H),
2.98 - 2.90 (m, 4H), 1.88 - 1.08 (m, 4H), 1.08 - 1.0 3 (m, 6H); 13C NMR (101
MHz, CDCl3) δ 155.90, 155.64, 151.58, 151.55, 134.00, 129.41, 123.76, 122.02,
121.38, 112.40, 77.32, 77.00, 76.68, 36.60, 36.55, 23.01, 22.36, 14.10,
14.03; HRES (m/z) (ESI): calcd for C16H19N2O [M+H]+ 255.1497, found 255.1494。
Claims (3)
1. a kind of synthetic method of benzofuran [2,3-b] pyrazines derivatives, which is characterized in that its synthetic method general formula is as follows:
R1 =H, aromatic radical, fat-based；
R2 =fat-based, aromatic radical；
Wherein, Pd catalyst are as follows: Pd NPs/POL-xantphos；
Sylvite are as follows: potassium carbonate, potassium phosphate, potassium acetate；
Solvent are as follows: N,N-dimethylformamide, 1,2- dichloroethanes, 1,4- dioxane, acetonitrile, toluene；
The universal synthesis method of benzofuran [2,3-b] pyrazines derivatives is:
(1) the adjacent halogen phenol of 0.2 mmol and the benzyl isonitrile of 0.3 mmol are first added in tube sealing, the Pd for adding 2 mol% is urged
Agent, the 2-3 times of sylvite measured and 1 milliliter of solvent react 6 ~ 12 h, TLC monitoring reaction at 100-150 DEG C；
(2) after complete reaction, it is cooled to room temperature, filters, finally uses anhydrous Na2SO4Dry, product at reduced pressure removes solvent, remaining
Object purifies to obtain benzofuran [2,3-b] pyrazines derivatives through Flash silica column analysis layer.
2. a kind of synthetic method of benzofuran [2,3-b] pyrazines derivatives according to claim 1, it is characterised in that:
Step (2) the Flash silica column chromatographic purifying, eluant, eluent is ethyl acetate: petroleum ether=1:100-200.
3. a kind of synthetic method of benzofuran [2,3-b] pyrazines derivatives according to claim 1, it is characterised in that:
The structural formula of benzofuran [2,3-b] pyrazines derivatives that step (2) obtains is as follows:
。
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| CN105884786A (en) * | 2016-05-13 | 2016-08-24 | 苏州大学 | Benzofuran [2,3-b ] pyrazine derivative and application thereof in organic electroluminescent device |
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