CN112679420B - Preparation method of 2,5-dibromopyridine - Google Patents
Preparation method of 2,5-dibromopyridine Download PDFInfo
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- CN112679420B CN112679420B CN202011572053.2A CN202011572053A CN112679420B CN 112679420 B CN112679420 B CN 112679420B CN 202011572053 A CN202011572053 A CN 202011572053A CN 112679420 B CN112679420 B CN 112679420B
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- dibromopyridine
- brominating reagent
- hydroxy
- bromopyridine
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- ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 18
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 13
- NDMZZQRNZFWMEZ-UHFFFAOYSA-N 5-bromo-1h-pyridin-2-one Chemical compound OC1=CC=C(Br)C=N1 NDMZZQRNZFWMEZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000011968 lewis acid catalyst Substances 0.000 claims abstract description 7
- 238000001953 recrystallisation Methods 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical group CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 238000010791 quenching Methods 0.000 claims description 4
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 230000000171 quenching effect Effects 0.000 claims description 3
- MXSVLWZRHLXFKH-UHFFFAOYSA-N triphenylborane Chemical compound C1=CC=CC=C1B(C=1C=CC=CC=1)C1=CC=CC=C1 MXSVLWZRHLXFKH-UHFFFAOYSA-N 0.000 claims description 3
- OBAJXDYVZBHCGT-UHFFFAOYSA-N tris(pentafluorophenyl)borane Chemical group FC1=C(F)C(F)=C(F)C(F)=C1B(C=1C(=C(F)C(F)=C(F)C=1F)F)C1=C(F)C(F)=C(F)C(F)=C1F OBAJXDYVZBHCGT-UHFFFAOYSA-N 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 2
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005893 bromination reaction Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000006193 diazotization reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- YDUGVOUXNSWQSW-UHFFFAOYSA-N 3-bromo-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1Br YDUGVOUXNSWQSW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
The invention discloses a preparation method of 2,5-dibromopyridine, and belongs to the technical field of organic synthesis. 2-hydroxy pyridine is taken as a raw material to react with a brominating reagent to obtain 2-hydroxy-5-bromopyridine; then reacts with brominating reagent under the action of Lewis acid catalyst to obtain 2, 5-dibromopyridine. The method is completed in two steps, the isomer obtained in the first step does not need to be purified, and the product with the purity of more than 99.5% can be obtained in the last step through recrystallization once.
Description
Technical Field
The invention relates to a preparation method of 2,5-dibromopyridine, belonging to the technical field of medicine synthesis.
Background
Pyridine derivatives are widely used in the synthesis of pesticides, medicines and natural products, such as antibiotics, antitumor drugs, antiulcer drugs, antihypertensive drugs and the like. The pyridine ring and the benzene ring are bioisosteres, and the pyridine ring has higher biological activity and smaller toxic and side effects. Pyridine derivatives are a general potential basic unit of nitrogen-containing bioactive molecules. The alkaloid contains a saturated six-membered nitrogen heterocyclic structure, so that an alkaloid skeleton unit can be skillfully constructed through pyridine derivatives, and the method has important significance for synthesizing the nitrogen heterocyclic alkaloid.
2,5-dibromopyridine, english name: 2, 5-Dibronoperidine, CAS 624-28-2, is used as pyridine skeleton intermediate, and bromine at 2-position and 5-position can be subjected to substitution reaction, coupling reaction and other reactions, and is widely used in medicine, pesticide, perfume and other aspects.
Hitherto reported methods for synthesizing 2,5-dibromopyridine [ Synthesis,2015,47,3169-3178], [ Journal of Organic Chemistry,2012,77,6908-6916] and WO2012/162818A1 are by bromination reaction and diazotization reaction, the reaction routes are as follows:
the method has the advantages that the yield of each step is about 85%, but the method has the defects that diazonium salt is unstable and high in activity, is easy to decompose and explode under the condition of heated collision, is unfavorable for safety and environmental protection, and has more waste water in the post-treatment process, thereby being unfavorable for industrial development.
However, in the above synthetic route, diazonium salt generated by diazotization reaction is unstable, and is easy to decompose and explode under the action of light and heat, so that the problem of safe industrial production and the like exists, and therefore, it is necessary to conduct intensive research on the synthetic process of 2,5-dibromopyridine, a better, safe and stable reaction route is provided, and industrial production is met, so as to meet the increasing market demand.
Disclosure of Invention
In order to overcome the technical defects, the invention provides a preparation method of 2, 5-dibromopyridine. 2-hydroxy pyridine is taken as a raw material to react with a brominating reagent to obtain 2-hydroxy-5-bromopyridine; then reacts with brominating reagent under the action of Lewis acid catalyst to obtain 2, 5-dibromopyridine. The method is completed in two steps, the isomer obtained in the first step does not need to be purified, and the product with the purity of more than 99.5% can be obtained in the last step through recrystallization once.
The preparation method of the 2,5-dibromopyridine comprises the following steps: adding 2-hydroxypyridine into an organic solvent, adding a brominating reagent in batches, quenching and filtering to obtain 2-hydroxy-5-bromopyridine; then adding the mixture into an organic solvent, reacting with a brominating reagent in the presence of a Lewis acid catalyst, and recrystallizing the obtained crude product by using a mixed solvent to obtain 2, 5-dibromopyridine; the reaction equation is expressed as follows:
further, in the above technical scheme, the organic solvent is selected from 1, 2-dichloroethane or acetonitrile, and the brominating reagent is selected from NBS and dibromohydantoin; the reaction temperature is between-10 and 25 ℃.
Further, in the above technical scheme, the molar ratio of the 2-hydroxypyridine to the brominating reagent is 1:0.60-1.00.
Further, in the above technical scheme, the organic solvent is selected from 1, 2-dichloroethane or acetonitrile, the lewis acid catalyst is selected from tris (pentafluorophenyl) borane or triphenylborane, and the brominating reagent is selected from phosphorus tribromide or phosphorus tribromide. Phosphorus tribromide is preferably used.
Further, in the above technical scheme, the molar ratio of the 2-hydroxy-5-bromopyridine to the catalyst to the brominating reagent is 1:0.05-0.10:1.10-1.30; the reaction is carried out under reflux conditions.
Further, in the above technical scheme, the recrystallization solvent is a mixed solvent of isopropanol and water.
Advantageous effects of the invention
The method is completed in two steps, and in the first step, the bromination reaction of the hydroxy para substituent is carried out, so that the regioselectivity is high and can reach 94/6, and the purification is not needed. In the second step, the product with purity more than 99.5% can be obtained by the reaction with brominating reagent under the catalysis of Lewis acid, the dosage of brominating reagent is almost equivalent, and the recrystallization.
The diazotization reaction with great potential safety hazard is not involved in the route, the operation is easy, the total yield can reach 80%, the wastewater production amount is greatly reduced, and the method is green and environment-friendly and is suitable for industrial production.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The invention is further illustrated by the following specific examples. These examples should be construed as merely illustrative of the present invention and not limiting the scope of the present invention. Various changes and modifications to the present invention may be made by one skilled in the art after reading the description herein, and such equivalent changes and modifications are intended to fall within the scope of the present invention as defined in the appended claims.
Example 1
Into the reaction flask, 50g (0.526 mol) of 2-hydroxypyridine and 250mL of acetonitrile were charged, 93.6g (0.526 mol) of NBS was added in portions at a temperature of-10 to 0℃and after the addition was completed, the temperature was raised to 15 to 25℃and the reaction was carried out for 1 hour. Detecting the reaction completion of the raw materials by sampling HPLC, and the proportion of the product 2-hydroxy-5-bromopyridine to the isomer 2-hydroxy-3-bromopyridineIs 94:6. concentrating the reaction solution at 45 ℃ under reduced pressure, heating the rest materials to 50 ℃ to dissolve the materials, measuring the pH=6.0-7.0, controlling the temperature to 45-50 ℃ and adding 750mL of water, slowly cooling to 20-25 ℃, precipitating the materials, stirring for 3 hours at the temperature, and filtering. The filter cake was rinsed with water and petroleum ether and dried to give 82.6g of 2-hydroxy-5-bromopyridine in 90.3% yield by HPLC:95.6%. 1 HNMR(400MHz,CDCl 3 ):11.73(s,1H),7.70(d,1H),7.56-7.51(m,1H),6.36(d,1H).
Example 2
50g (0.526 mol) of 2-hydroxypyridine and 200ml of 1, 2-dichloroethane are put into a reaction flask, 90g (0.315 mol) of dibromohydantoin is added in portions at a temperature of between-10 and 0 ℃ and then the temperature is raised to between 20 and 25 ℃ after the addition is completed, and the reaction is carried out for 1.5 hours. After the reaction of the raw materials is detected by sampling HPLC, the proportion of the product 2-hydroxy-5-bromopyridine to the isomer 2-hydroxy-3-bromopyridine is 93:7. aqueous sodium bisulphite is added to quench, the layers are separated, the aqueous phase is extracted with 1, 2-dichloroethane, the organic phases are combined, washed with water to ph=6.0-7.0, and the organic phases are dried over anhydrous sodium sulfate to give 435g of 1, 2-dichloroethane solution containing 2-hydroxy-5-bromopyridine, hplc:92.6% and yield 92.0%; and (5) carrying out bromination in the next step.
Example 3
50g (0.287 mol) of 2-hydroxy-5-bromopyridine, 7.3g (0.014 mol) of tris (pentafluorophenyl) borane and 200mL of acetonitrile were charged into the reaction flask under nitrogen protection, 93.2g (0.344 mol) of phosphorus tribromide was added dropwise at room temperature, and the mixture was slowly warmed to reflux after the completion of the dropwise addition, and reacted for 5 hours. Detecting that the raw materials react, concentrating under reduced pressure at 55deg.C until no liquid flows, pouring the residual liquid into 200mL ice water, adding saturated sodium carbonate solution to adjust pH=8.0-9.0, extracting with dichloromethane, concentrating the solvent under reduced pressure, adding 35mL isopropanol for replacement, heating to 50deg.C, adding 100mL water, and slowly cooling to precipitateThe solid was filtered and the filter cake was dried to give 56.3g of 2,5-dibromopyridine in 82.7% yield by HPLC:99.7%. 1 HNMR(400MHz,CDCl 3 )：8.81(d,1H),8.35(d,1H),8.13(d,1H).
Example 4
Under the protection of nitrogen, 435g of the 2-hydroxy-5-bromopyridine/1, 2-dichloroethane-containing solution of example 2 and 11.7g (0.048 mol) of triphenylborane were put into a reaction flask, and 131g (0.484 mol) of phosphorus tribromide was added dropwise, and after the completion of the dropwise addition, the temperature was slowly raised to reflux for 10 hours. After the detection reaction is finished, pouring the residual liquid into 200mL of ice water for quenching, adding 10% sodium hydroxide aqueous solution to adjust the pH value to be 8.0-9.0, washing an organic phase with water, concentrating dichloromethane under reduced pressure, replacing with 55mL of isopropanol, heating to 50 ℃, adding 160mL of water, slowly cooling to precipitate solid, filtering, drying a filter cake to obtain 101.6g of 2,5-dibromopyridine, and obtaining 88.7% yield by HPLC:99.5%.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should be covered by the protection scope of the present invention by making equivalents and modifications to the technical solution and the inventive concept thereof.
Claims (3)
1. The preparation method of the 2,5-dibromopyridine is characterized by comprising the following reaction routes:
the method comprises the following steps: adding 2-hydroxypyridine into an organic solvent, adding a brominating reagent in batches, quenching and filtering to obtain 2-hydroxy-5-bromopyridine; then adding the mixture into an organic solvent, reacting with a brominating reagent in the presence of a Lewis acid catalyst, and recrystallizing the obtained crude product by using a mixed solvent to obtain 2, 5-dibromopyridine; the organic solvent is selected from 1, 2-dichloroethane or acetonitrile, the Lewis acid catalyst is selected from tris (pentafluorophenyl) borane or triphenylborane, and the brominating reagent is selected from phosphorus tribromide or phosphorus tribromide oxide; the molar ratio of the 2-hydroxy-5-bromopyridine to the Lewis acid catalyst to the brominating reagent is 1:0.05-0.10:1.10-1.30; the recrystallization adopts a mixed solvent composed of isopropanol and water.
2. The method for preparing 2,5-dibromopyridine according to claim 1, wherein: the brominating reagent is selected from NBS and dibromohydantoin.
3. The method for preparing 2,5-dibromopyridine according to claim 1, wherein: the molar ratio of the 2-hydroxypyridine to the brominating reagent is 1:0.60-1.00.
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| CN113461603A (en) * | 2021-07-01 | 2021-10-01 | 南京超逸生物科技有限公司 | Synthetic method of medicine raw material 2, 5-dibromopyridine |
| CN113402451A (en) * | 2021-07-04 | 2021-09-17 | 南京超逸生物科技有限公司 | Preparation method of 2, 5-dibromopyridine |
| CN113773291B (en) * | 2021-10-09 | 2023-04-25 | 上海昕凯医药科技有限公司 | Improved synthesis method of glass color factor of cosmetic active ingredient |
| CN114591225B (en) * | 2022-03-02 | 2024-02-06 | 河南阿尔法医药科技有限公司 | Method for large-scale production of 2, 6-dibromo-4-methylpyridine |
| CN116003407B (en) * | 2022-12-27 | 2025-04-01 | 株洲千金药业股份有限公司 | A synthetic method for large-scale production of zolpidem |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105061301A (en) * | 2015-09-07 | 2015-11-18 | 陈吉美 | Synthesis method of 2,5-dibromopyridine |
| WO2018231627A1 (en) * | 2017-06-12 | 2018-12-20 | Viamet Pharmaceuticals (NC), Inc. | 2,5-dibromopyridine and processes of preparation |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105061301A (en) * | 2015-09-07 | 2015-11-18 | 陈吉美 | Synthesis method of 2,5-dibromopyridine |
| WO2018231627A1 (en) * | 2017-06-12 | 2018-12-20 | Viamet Pharmaceuticals (NC), Inc. | 2,5-dibromopyridine and processes of preparation |
Non-Patent Citations (3)
| Title |
|---|
| C. Scott Shultz 等.Practical Synthesis of a Potent Bradykinin B1 Antagonist via Enantioselective Hydrogenation of a PyridylN-Acyl Enamide.《J. Org. Chem.》.2009,第74卷4547-4553. * |
| Mercedes Santos 等.Mild Regioselective Halogenation of Activated Pyridines with NBromosuccinimide.《Synthesis 》.2001,第14卷2176页table，2177页制备方法. * |
| 刘鹰翔.《药物合成反应》.中国中医药出版社,2017,(第第1版版),66-75. * |
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