CN111056979A - 3-cyclopropylbenzenesulfonyl benzylamine and synthesis method thereof - Google Patents
3-cyclopropylbenzenesulfonyl benzylamine and synthesis method thereof Download PDFInfo
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- CN111056979A CN111056979A CN201911354941.4A CN201911354941A CN111056979A CN 111056979 A CN111056979 A CN 111056979A CN 201911354941 A CN201911354941 A CN 201911354941A CN 111056979 A CN111056979 A CN 111056979A
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- benzylamine
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- cyclopropylbenzenesulfonyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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Abstract
The invention discloses 3-cyclopropylbenzenesulfonyl benzylamine and a preparation method thereof, and the preparation method comprises the following steps: dissolving 3-bromobenzenesulfonic acid and benzylamine in pyridine, adding a condensing agent EDC-HCl, and reacting at 50-80 ℃ for 2-3 h to obtain 3-bromo-N-benzylbenzenesulfonamide; dissolving 3-bromo-N-benzylbenzenesulfonamide in dioxane solution, adding cyclopropylboronic acid, sodium carbonate and water, Pd (dppf) Cl2The mixed system reacts for 8-10h at 110 ℃ in the nitrogen atmosphere, and is subjected to post-treatment to obtain the 3-cyclopropylbenzenesulfonyl benzylamine.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to 3-cyclopropylbenzenesulfonyl benzylamine and a preparation method thereof.
Background
The sulfonamide compound is an important medicine branch, is commonly present in anti-inflammatory and antibacterial medicine structures, and various substitutions and derivatives thereof are also widely present in medicine molecules, so that the sulfonamide compound has important pharmaceutical value for preparation and research of the sulfonamide compound. However, the synthetic literature of cyclopropyl substituted benzene sulfonamide compounds is less reported, mainly because the introduction of cyclopropyl substituent is difficult, the steps are long, the reagent is expensive, the operation is not easy, and the like. The research on the type and the synthesis method of the 3-cyclopropylbenzenesulfonyl benzylamine is not reported in the literature at present. The synthesis route disclosed by the invention is short, the preparation method is easy to operate, the yield is good, and the preparation method is suitable for mass preparation. The present disclosure has significant research and utility values as such compounds are valuable pharmaceutical intermediates.
Disclosure of Invention
The invention aims to provide 3-cyclopropylbenzenesulfonyl benzylamine and a preparation method thereof, and the prepared 3-cyclopropylbenzenesulfonyl benzylamine has certain drug research value, is easy to operate in reaction and is suitable for batch preparation.
In order to achieve the purpose, the invention adopts the following technical scheme:
3-cyclopropylbenzenesulfonyl benzylamine, wherein the structural formula of the 3-cyclopropylbenzenesulfonyl benzylamine is shown in the specification
The preparation method of the novel compound 3-cyclopropylbenzenesulfonyl benzylamine comprises the following steps:
(1) dissolving 3-bromobenzenesulfonic acid and benzylamine in pyridine, adding a condensing agent EDC-HCl, and reacting at 50-80 ℃ for 2-3 h to obtain 3-bromo-N-benzylbenzenesulfonamide;
(2) dissolving 3-bromo-N-benzylbenzenesulfonamide in dioxane solution, adding cyclopropylboronic acid, sodium carbonate, Pd (dppf) Cl2Reacting the mixed system at 110 ℃ for 8-10h in a nitrogen atmosphere, and performing post-treatment to obtain 3-cyclopropylbenzenesulfonyl benzylamine;
the specific reaction equation is as follows:
further, the mole ratio of the benzylamine, the 3-bromobenzenesulfonic acid and the condensing agent EDC-HCl in the step (1) is 1: 1.5-1: 1.2: 2.
Further, in the step (2), 3-bromo-N-benzylbenzenesulfonamide is reacted with cyclopropylboronic acid, sodium carbonate, Pd (dppf) Cl2The molar ratio of (1: 1:2: 0.05) to (1: 1:5: 0.1).
The invention has the beneficial effects that: 3-cyclopropylbenzenesulfonyl benzylamine is an important drug intermediate with potential pharmacological activity. The preparation method provided by the invention is easy to operate, high in product yield and suitable for batch preparation, so that the preparation method of the 3-cyclopropylbenzenesulfonyl benzylamine has important application value.
Detailed Description
The present invention will be further described with reference to the following examples. It is to be understood that the following examples are illustrative only and are not intended to limit the scope of the invention, which is to be given numerous insubstantial modifications and adaptations by those skilled in the art based on the teachings set forth above.
Example 1
The preparation of 3-cyclopropylbenzenesulfonylbenzylamine of this example was as follows:
(1) synthesis of 3-bromo-N-benzylbenzenesulfonamide
Adding 4.74g (0.02 mol) of 3-bromobenzenesulfonic acid into a 100mL single-neck bottle, adding 100mL of pyridine, stirring for dissolving, adding 2.14g (0.02 mol) of benzylamine, slowly adding 5.73g (0.03 mol) of condensation agent EDC-HCl into the reaction liquid in batches, heating to 50 ℃ for reacting for 4 hours, removing pyridine by rotary evaporation, pouring residual water into a separating funnel, adding a proper amount of ethyl acetate into the separating funnel for extraction for 3 times, washing an ethyl acetate layer with diluted hydrochloric acid for 1 time, combining organic layers, drying the organic layer by anhydrous sodium sulfate, and removing the solvent under reduced pressure to obtain 5.98g of white solid with the yield of 92%;
MS：m/z: [M+1]: 327，329。
1H NMR (400 MHz, DMSO-d6)：7.78（m, IH）, 7.74（br, 1H）, 7.62-7.60（m,2H）, 7.23-7.33（m, 5H）, 3.98（s, 2H）。
elemental analysis C13H12BrNO2C, 47.86, H, 3.71, Br, 24.49, N, 4.29, O, 9.81 and S, 9.83.
Measured values of C, 47.70, H, 3.77, Br, 24.65, N, 4.13, S, 9.50.
(2) Synthesis of 3-cyclopropylbenzenesulfonylbenzylamine
3.26g (0.01 mol) of 3-bromo-N-benzylbenzenesulfonamide was weighed, 15mL of dioxane and 5mL of water were added, and after stirring and dissolution, 0.86g (0.01 mol) of cyclopropylboronic acid, 2.12g (0.02 mol) of sodium carbonate and Pd (dppf) Cl were weighed20.37g (0.0005 mol) was added to the reaction system, which was then purged with nitrogen 3 times, and the reaction temperature was set at 110 ℃ for 8 hours. After the reaction is finished, evaporating the solvent under reduced pressure, adding a proper amount of water and ethyl acetate into the residue, extracting for 3 times, drying the extract liquor by using anhydrous sodium sulfate, removing the solvent by using a rotary evaporator, and purifying the obtained residue by using a column to obtain 2.37g of a white body with the yield of 89%;
MS：m/z: [M+1]: 288。
1H NMR (400 MHz, DMSO-d6)：7.84（s, 1H）, 7.74（br, 1H）, 7.84-7.65（m,3H）, 7.23-7.33 (m, 6H), 3.99（s, 2H）, 1.50（m, 1H）, 1.24（m, 2H）, 0.98（m, 2H）。
elemental analysis C16H17NO2C, 66.87, H, 5.96, N, 4.87, O, 11.13 and S, 11.16.
Measured values of C, 66.79, H, 5.84, N, 4.90, S, 11.02.
Example 2
The preparation of 3-cyclopropylbenzenesulfonylbenzylamine of this example was as follows:
(1) synthesis of 4-bromo-N-benzylbenzenesulfonamide
Adding 4.74g (0.02 mol) of 3-bromobenzenesulfonic acid into a 100mL single-neck bottle, adding 100mL of pyridine, stirring to dissolve, adding 2.04g (0.022 mol) of benzylamine, slowly adding 5.73g (0.03 mol) of condensation agent EDC-HCl into the reaction liquid in batches, heating to 50 ℃ to react for 2 hours, removing pyridine by rotary evaporation, pouring residual water into a separating funnel, adding a proper amount of ethyl acetate into the separating funnel to extract for 3 times, washing an ethyl acetate layer with diluted hydrochloric acid for 1 time, combining organic layers, drying the organic layer by anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain 5.72g of white solid, wherein the yield is 88%;
(2) synthesis of 3-cyclopropylbenzenesulfonylbenzylamine
3.26g (0.01 mol) of 3-bromo-N-benzylbenzenesulfonamide was weighed, 15mL of dioxane and 5mL of water were added, and after stirring and dissolution, 0.86g (0.01 mol) of cyclopropylboronic acid, 2.12g (0.03 mol) of sodium carbonate and Pd (dppf) Cl were weighed20.37g (0.0005 mol) was added to the reaction system, which was then purged with nitrogen 3 times, and the reaction temperature was set at 110 ℃ for 8 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and then, an appropriate amount of water and ethyl acetate were added to the residue to extract 3 times, and after the extract was dried with anhydrous sodium sulfate, the solvent was removed by a rotary evaporator, and the obtained residue was purified by column chromatography to obtain 2.56g of a white substance with a yield of 89%.
Example 3
The preparation of 3-cyclopropylbenzenesulfonylbenzylamine of this example was as follows:
(1) synthesis of 3-bromo-N-benzylbenzenesulfonamide
Adding 4.74g (0.02 mol) of 3-bromobenzenesulfonic acid into a 100mL single-neck bottle, adding 100mL of pyridine, stirring to dissolve, adding 2.23g (0.024 mol) of benzylamine, slowly adding 5.73g (0.03 mol) of condensation agent EDC-HCl into the reaction liquid in batches, heating to 50 ℃ to react for 2 hours, removing pyridine by rotary evaporation, pouring residual water into a separating funnel, adding a proper amount of ethyl acetate into the separating funnel to extract for 3 times, washing an ethyl acetate layer with diluted hydrochloric acid for 1 time, combining organic layers, drying the organic layers by anhydrous sodium sulfate, and removing the solvent under reduced pressure to obtain 5.78g of white solid with the yield of 89%;
(2) synthesis of 3-cyclopropylbenzenesulfonylbenzylamine
3.26g (0.01 mol) of 3-bromo-N-benzylbenzenesulfonamide was weighed out, and 15m dioxane was addedL, 5mL of water, after stirring and dissolving, 0.86g (0.01 mol) of cyclopropylboronic acid, 2.12g (0.04 mol) of sodium carbonate, Pd (dppf) Cl were weighed20.58g (0.0008 mol) was added to the reaction system, which was then purged with nitrogen 3 times, and the reaction temperature was set at 110 ℃ for 9 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and then, an appropriate amount of water and ethyl acetate were added to the residue to extract 3 times, and after the extract was dried with anhydrous sodium sulfate, the solvent was removed by a rotary evaporator, and the obtained residue was purified by column chromatography to obtain 2.62g of a white substance with a yield of 91%.
Example 4
The preparation of 3-cyclopropylbenzenesulfonylbenzylamine of this example was as follows:
(1) synthesis of 3-bromo-N-benzylbenzenesulfonamide
Adding 4.74g (0.02 mol) of 3-bromobenzenesulfonic acid into a 100mL single-neck bottle, adding 100mL of pyridine, stirring to dissolve, adding 2.23g (0.024 mol) of benzylamine, slowly adding 6.9g (0.036 mol) of condensation agent EDC-HCl into the reaction liquid in batches, heating to 50 ℃ to react for 2 hours, removing pyridine by rotary evaporation, pouring residual water into a separating funnel, adding a proper amount of ethyl acetate to extract for 3 times, washing an ethyl acetate layer with diluted hydrochloric acid for 1 time, combining organic layers, drying the organic layer by anhydrous sodium sulfate, removing the solvent under reduced pressure to obtain 5.98g of white solid with the yield of 92%;
(2) synthesis of 3-cyclopropylbenzenesulfonylbenzylamine
3.26g (0.01 mol) of 3-bromo-N-benzylbenzenesulfonamide was weighed, 15mL of dioxane and 5mL of water were added, and after stirring and dissolution, 0.86g (0.01 mol) of cyclopropylboronic acid, 2.12g (0.04 mol) of sodium carbonate and Pd (dppf) Cl were weighed21.16g (0.001 mol) was added to the reaction system, which was then replaced with nitrogen 3 times, and the reaction temperature was set at 110 ℃ for 10 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and then, an appropriate amount of water and ethyl acetate were added to the residue to extract 3 times, and after the extract was dried with anhydrous sodium sulfate, the solvent was removed by a rotary evaporator, and the obtained residue was purified by column chromatography to obtain 2.67g of a white substance with a yield of 92.8%.
Example 5
The preparation of 3-cyclopropylbenzenesulfonylbenzylamine of this example was as follows:
(1) synthesis of 3-bromo-N-benzylbenzenesulfonamide
A100 mL single-neck bottle is taken, 4.74g (0.02 mol) of 3-bromobenzenesulfonic acid is added, 100mL of pyridine is added, stirring is carried out for dissolution, 2.23g (0.024 mol) of benzylamine is added, 5.73g (0.04 mol) of condensation agent EDC-HCl is slowly added into the reaction liquid in batches, the mixture is heated to 50 ℃ for reaction for 2 hours, pyridine is removed by rotary evaporation, residual water is poured into a separating funnel, a proper amount of ethyl acetate is added into the mixture for extraction for 3 times, an ethyl acetate layer is washed with diluted hydrochloric acid for 1 time, organic layers are combined, the organic layer is dried by anhydrous sodium sulfate, and then the solvent is removed under reduced pressure, so that 6.24g of white solid is obtained, and the yield is 96%.
(2) Synthesis of 3-cyclopropylbenzenesulfonylbenzylamine
3.26g (0.01 mol) of 3-bromo-N-benzylbenzenesulfonamide was weighed, 15mL of dioxane and 5mL of water were added, and after stirring and dissolution, 0.86g (0.01 mol) of cyclopropylboronic acid, 2.12g (0.05 mol) of sodium carbonate and Pd (dppf) Cl were weighed21.16g (0.001 mol) was added to the reaction system, which was then replaced with nitrogen 3 times, and the reaction temperature was set at 110 ℃ for 10 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and then, an appropriate amount of water and ethyl acetate were added to the residue to extract 3 times, and after the extract was dried with anhydrous sodium sulfate, the solvent was removed by a rotary evaporator, and the obtained residue was purified by column chromatography to obtain 2.73g of a white substance with a yield of 95%.
The foregoing shows and describes the general principles and features of the present invention, together with the advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (4)
1.3-cyclopropylbenzenesulfonylbenzylamine, characterized by: the structural formula of the 3-cyclopropylbenzenesulfonyl benzylamine is shown in the specification
2. A process for producing 3-cyclopropylbenzenesulfonylbenzylamine according to claim 1, characterized by the following steps:
(1) dissolving 3-bromobenzenesulfonic acid and benzylamine in pyridine, adding EDC-HCl, and reacting at 50-80 ℃ for 2-3 h to obtain 3-bromo-N-benzylbenzenesulfonamide;
(2) dissolving 3-bromo-N-benzylbenzenesulfonamide in dioxane solution, adding cyclopropylboronic acid, sodium carbonate, Pd (dppf) Cl2Reacting the mixed system for 8-10h at 110 ℃ in the nitrogen atmosphere, and performing post-treatment to obtain 3-cyclopropylbenzenesulfonyl benzylamine;
the specific reaction equation is as follows:
3. the method for producing 3-cyclopropylbenzenesulfonylbenzylamine according to claim 2, characterized in that: the molar ratio of benzylamine, 3-bromobenzenesulfonic acid and condensing agent EDC-HCl in the step (1) is 1:1: 1.5-1: 1.2: 2.
4. The method for producing 3-cyclopropylbenzenesulfonylbenzylamine according to claim 2, characterized in that: in the step (2), the 3-bromine-N-benzyl benzene sulfonamide is mixed with cyclopropyl boric acid, sodium carbonate, Pd (dppf) Cl2The molar ratio of (1: 1:2: 0.05-1: 1.1:5: 0.1).
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101065353A (en) * | 2004-11-26 | 2007-10-31 | 巴斯福股份公司 | Novel 2-cyano-3-(halo)alkoxy-benzenesulfonamide compounds for combating animal pests |
| CN101808983A (en) * | 2007-09-27 | 2010-08-18 | 霍夫曼-拉罗奇有限公司 | biaryl sulfonamide derivatives |
| CN102391059A (en) * | 2011-08-12 | 2012-03-28 | 郑州泰基鸿诺药物科技有限公司 | Method for synthesizing cyclopropyl alkyl aromatic compound |
| US20180146666A1 (en) * | 2016-11-28 | 2018-05-31 | The Regents Of The University Of California | Aba receptor agonists that modulate transpiration |
| WO2018132372A1 (en) * | 2017-01-10 | 2018-07-19 | Sanford Burnham Prebys Medical Discovery Institute | Small molecule activators of nicotinamide phosphoribosyltransferase (nampt) and uses thereof |
| CN108409612A (en) * | 2018-03-21 | 2018-08-17 | 福建医科大学 | A kind of method that N- benzyl benzenesulfonamides are catalyzed and synthesized by boric acid/Catalyzed by Oxalic Acid system under microwave radiation |
| CN110551147A (en) * | 2019-09-29 | 2019-12-10 | 蚌埠产品质量监督检验研究院 | synthetic method of 3-cyclopropylphenylboronic acid |
-
2019
- 2019-12-25 CN CN201911354941.4A patent/CN111056979A/en not_active Withdrawn
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101065353A (en) * | 2004-11-26 | 2007-10-31 | 巴斯福股份公司 | Novel 2-cyano-3-(halo)alkoxy-benzenesulfonamide compounds for combating animal pests |
| CN101808983A (en) * | 2007-09-27 | 2010-08-18 | 霍夫曼-拉罗奇有限公司 | biaryl sulfonamide derivatives |
| CN102391059A (en) * | 2011-08-12 | 2012-03-28 | 郑州泰基鸿诺药物科技有限公司 | Method for synthesizing cyclopropyl alkyl aromatic compound |
| US20180146666A1 (en) * | 2016-11-28 | 2018-05-31 | The Regents Of The University Of California | Aba receptor agonists that modulate transpiration |
| WO2018132372A1 (en) * | 2017-01-10 | 2018-07-19 | Sanford Burnham Prebys Medical Discovery Institute | Small molecule activators of nicotinamide phosphoribosyltransferase (nampt) and uses thereof |
| CN108409612A (en) * | 2018-03-21 | 2018-08-17 | 福建医科大学 | A kind of method that N- benzyl benzenesulfonamides are catalyzed and synthesized by boric acid/Catalyzed by Oxalic Acid system under microwave radiation |
| CN110551147A (en) * | 2019-09-29 | 2019-12-10 | 蚌埠产品质量监督检验研究院 | synthetic method of 3-cyclopropylphenylboronic acid |
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