CN1762984A - Purification method for amide and sulfonylamine compound synthesized from liquid phase - Google Patents
Purification method for amide and sulfonylamine compound synthesized from liquid phase Download PDFInfo
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Abstract
The purification process of amide and sulfamide compound synthesized in solution phase includes the following steps: 1. dissolving 1 mmol amine compound in 3-5 ml methane dichloride via stirring, adding 2-2.5 mmol benzoyl chloride or 4-tolylsulfonyl chloride, adding 2-3 mmol triethylamine or pyridine, stirring under room temperature, and tracing the reaction process via vapor chromatographic method until finishing reaction; and 2. adding 1.2-2.0 mmol water soluble N-aminoethyl pyridinium as nucleophilic amino eliminator via stirring at room temperature, adding 10-15 ml ethyl acetate to dilute reacted liquid, washing with 10-15 ml salt water, penetrating the organic phase through silicon gel column, drying with anhydrous sodium sulfate and drying. The present invention adopts water soluble ionic compound as eliminator carrier and water to wash reaction product to reach the aim of purification. The eliminator is easy to prepare and purify, low in cost, high in reaction activity, high in purifying efficiency and suitable for mass synthesis.
Description
Technical field
The present invention relates to the purification process of combined synthesizing amide of a kind of solution and sulfamide compound.
Background technology
In recent years, combinatorial chemistry has greatly promoted the development of pharmaceutical chemistry and materials chemistry, provides very effective means for seeking the new drug lead compound and preparing the material with specific function.Compare with the solid phase combination is synthetic, combined synthesizing of solution has plurality of advantages: (1) reaction type is many, and it is combined synthetic that existing reaction all can be used for solution; (2) need not to design synthetic link molecule and cleaved products; (3) the easy tracking and the detection reaction process; (4) need not many times of excessive reagent and a large amount of cleaning solvents, cost is low, is easy to realize a large amount of synthetic.But, how to realize that fast separating and purifying target compound storehouse is the key issue that the combined chemistry of solution will solve.In the combined synthetic separating and purifying technology of solution, it is the method for widespread use that polymkeric substance load scavenging agent (polymer-supported scavenger) is assisted separation and purification.This method uses close electricity such as isocyanic ester excessive in the resin of functionalization and the solution-phase reaction, carboxylic acid halides, amine or nucleophilic reagent to react, and reaches the purpose of purifies and separates by removing by filter the product resin.Though it is simple to operate, the charge capacity of scavenger resin is low, the cost height, be unsuitable for a large amount of synthetic, and the efficient of purifies and separates that had disadvantages affect such as " solid state reaction effects ".
Summary of the invention
The purification process that the purpose of this invention is to provide combined synthesizing amide of a kind of solution and sulfamide compound.
The step of method is as follows:
1) the 1mmol aminated compounds is dissolved in 3～5ml methylene dichloride under stirring, slowly add 2～3mmol triethylamine or pyridine after adding 2～2.5mmol Benzoyl chloride or 4-toluene sulfonyl chloride, mixing solutions at room temperature stirs, and follows the tracks of reaction process with gas-chromatography, and reaction finishes;
2) add the water miscible amino nucleophilicity scavenging agent bromination N-aminoethyl pyridinium salt of 1.2～2.0mmol, stirring at room 6～12 hours, add 10～15ml ethyl acetate dilute reaction solution also with 10～15ml salt water washing 2～3 times, after organic phase is passed 0.5～1cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain amides or sulfamide compound.
Described aminated compounds is aromatic amine compounds, fat amine compound.Aromatic amine compounds is aniline, 4-anisidine, 2-aminotoluene or N-ethylphenyl amine.Fat amine compound is benzylamine, morphine quinoline, amino dodecane, hexahydroaniline or hexahydropyridine.
The present invention adopts micromolecular water dissolubility ionic compound as the scavenging agent carrier, and the product of scavenging agent and cleaning reaction can separate with target compound by liquid-liquid phase extraction, reaches the purpose of purifying.This class scavenging agent is a raw material with pyridine and 2-bromine ethylamine hydrochloride, preparation and purifying easily, and cost is low, reactive behavior height, purification efficiency height (product purity height, yield height) and be suitable for a large amount of synthetic.
Embodiment
The present invention adopts water miscible combined synthetic acid amides of amino nucleophilicity scavenging agent purification solution and sulfamide compound, this class scavenging agent and excessive electrophilic reagent (acyl chlorides, SULPHURYL CHLORIDE) react, removing product that generates and excessive scavenging agent are removed (liquid-liquid phase extracting and separating) by washing, thereby reach the purpose of purified product, reaction formula is as follows:
The acid amides of the synthetic gained of the present invention and the yield of sulfamide compound and purity see Table 1 and table 2.
The combined synthesizing amide compounds of table 1 solution
| No | Amine | Product | Yield (%) | Purity (%) | Molecular weight (EI) (M +，m/z) |
| 1 | aniline | 5a | 87 | 97 | 197 |
| 2 | benzylamine | 5b | 84 | 92 | 211 |
| 3 | 4-methoxylaniline | 5c | 88 | 99 | 227 |
| 4 | 2-toluidine | 5d | 85 | 97 | 211 |
| 5 | morpholine | 5e | 88 | 98 | 191 |
| 6 | hexahydropyridine | 5f | 87 | 99 | 189 |
| 7 | cyclohexylamine | 5g | 86 | 99 | 203 |
| 8 | dodecylamine | 5h | 88 | 97 | 289 |
| 9 | N-ethylaniline | 5i | 83 | 99 | 225 |
The combined synthetic sulfamide compound of table 2 solution
| No | Amine | Product | Yield (%) | Purity (%) | Molecular weight (EI) (M +，m/z) |
| 1 | aniline | 7a | 83 | 95 | 247 |
| 2 | benzylamine | 7b | 85 | 99 | 261 |
| 3 | 4-methoxylaniline | 7c | 86 | 96 | 277 |
| 4 | cyclohexylamine | 7d | 84 | 99 | 253 |
| 5 | hexahydropyridine | 7e | 87 | 93 | 239 |
| 6 | morpholine | 7f | 88 | 99 | 241 |
| 7 | dodecylamine | 7g | 85 | 96 | 339 |
| 8 | 3-toluidine | 7h | 83 | 94 | 261 |
| 9 | N-ethylaniline | 7i | 82 | 97 | 275 |
Following examples will help to understand the present invention, but be not limited to content of the present invention:
Synthesizing of embodiment 1 water-soluble scavenging agent bromination N-aminoethyl pyridinium salt (1)
20.5g after (0.1mol) the pyridine Hybrid Heating of 2-bromine ethylamine hydrochloride and 50ml steaming newly refluxed 24 hours, pyridine was removed in underpressure distillation, portioning adding solid potassium hydroxide adjusting pH=8 after the adding 10ml water dissolution in the gained solid.The aqueous solution extracts product (30ml * 2) with ethyl acetate washing (30ml * 2), solid concentrated, dry gained with acetonitrile, merges the acetonitrile extracting solution, concentrates and obtains bromination N-aminoethyl pyridinium salt 18.3g, yield 90%.
mp：227.9～229.6℃
1H NMR(500MHz，D
2O)：δ3.43(t，2H，J＝6.0Hz)，4.80(t，2H，J＝6.0Hz)，8.10(m，2H)，8.58(m，1H)，8.89(m，2H)；
13C NMR(125MHz，D
2O)：δ40.89，61.43，128.98，145.00，146.76；
IR(KBr)：3555，3481，3418，1637，1618，1079，1036cm
-1.
MS(ESI)：m/z 123([M-Br]
+).
Embodiment 2 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-phenylbenzamaide
93mg (1mmol) aniline is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 171mg N-phenylbenzamaide, yield is 87%.It is 97% that GC/MS analyzes its purity.Molecular weight is 197.
Embodiment 3 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-benzyl benzamide
107mg (1mmol) benzylamine is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 10 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 177mg N-benzyl benzamide, yield is 84%.It is 92% that GC/MS analyzes its purity.Molecular weight is 211.
Embodiment 4 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-4-anisole yl-benzamide
123mg (1mmol) 4-anisidine is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 200mgN-4-anisole yl-benzamide, yield is 88%.It is 99% that GC/MS analyzes its purity.Molecular weight is 227.
Embodiment 5 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-2-aminomethyl phenyl benzamide
107mg (1mmol) 2-aminotoluene is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 12 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 179mgN-2-aminomethyl phenyl benzamide, yield is 85%.It is 97% that GC/MS analyzes its purity.Molecular weight is 211.
Embodiment 6 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic morphine quinoline yl-benzamide
87mg (1mmol) morphine quinoline is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 168mg morphine quinoline yl-benzamide, yield is 88%.It is 98% that GC/MS analyzes its purity.Molecular weight is 191.
Embodiment 7 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic hexahydropyridine yl-benzamide
85mg (1mmol) hexahydropyridine is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmo1) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 164mg hexahydropyridine yl-benzamide, yield is 87%.It is 99% that GC/MS analyzes its purity.Molecular weight is 189.
Embodiment 8 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-phenylcyclohexane methane amide
99mg (1mmol) hexahydroaniline is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 175mg N-phenylcyclohexane methane amide, yield is 86%.It is 99% that GC/MS analyzes its purity.Molecular weight is 203.
Embodiment 9 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-dodecyl benzamide
185mg (1mmol) lauryl amine is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 254mgN-dodecyl benzamide, yield is 88%.It is 97% that GC/MS analyzes its purity.Molecular weight is 289.
Embodiment 10 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-ethylphenyl benzamide
121mg (1mmol) N-ethylphenyl amine is dissolved in the 3ml methylene dichloride under stirring, slowly add 303mg (3mmol) triethylamine after adding 280mg (2mmol) Benzoyl chloride, mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 407mg (2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours, add 10ml ethyl acetate dilute reaction solution and use 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 187mg N-ethylphenyl benzamide, yield is 83%.It is 99% that GC/MS analyzes its purity.Molecular weight is 225.
Embodiment 11 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-phenyl-4-methyl benzenesulfonamide
93mg (1mmol) aniline is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 205mg N-phenyl-4-methyl benzenesulfonamide, yield is 83%.It is 95% that GC/MS analyzes its purity.Molecular weight is 247.
Embodiment 12 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-benzyl-4-methyl benzenesulfonamide
107mg (1mmol) benzylamine is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 222mg N-phenyl-4-methyl benzenesulfonamide, yield is 85%.It is 99% that GC/MS analyzes its purity.Molecular weight is 261.
Embodiment 13 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-4-p-methoxy-phenyl-4-methyl benzenesulfonamide
123mg (1mmol) 4-anisidine is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 238mgN-4-p-methoxy-phenyl-4-methyl benzenesulfonamide, yield is 86%.It is 96% that GC/MS analyzes its purity.Molecular weight is 277.
Embodiment 14 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-cyclohexyl-4-methyl benzenesulfonamide
99mg (1mmol) hexahydroaniline is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 213mg N-cyclohexyl-4-methyl benzenesulfonamide, yield is 84%.It is 99% that GC/MS analyzes its purity.Molecular weight is 253.
Embodiment 15 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic hexahydropyridine base-4-methyl benzenesulfonamide
85mg (1mmol) hexahydropyridine is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 208mg hexahydropyridine base-4-methyl benzenesulfonamide, yield is 87%.It is 93% that GC/MS analyzes its purity.Molecular weight is 239.
Embodiment 16 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic morphine quinoline base-4-methyl benzenesulfonamide
87mg (1mmol) morphine quinoline is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 407mg (2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 12 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 212mg morphine quinoline base-4-methyl benzenesulfonamide, yield is 88%.It is 99% that GC/MS analyzes its purity.Molecular weight is 241.
Embodiment 17 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-dodecyl-4-methyl benzenesulfonamide
185mg (1mmol) lauryl amine is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 288mgN-dodecyl-4-methyl benzenesulfonamide, yield is 85%.It is 96% that GC/MS analyzes its purity.Molecular weight is 339.
Embodiment 18 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-3-aminomethyl phenyl-4-methyl benzenesulfonamide
107mg (1mmol) 3-monomethylaniline is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 244mg (1.2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 6 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 217mgN-3-aminomethyl phenyl-4-methyl benzenesulfonamide, yield is 83%.It is 94% that GC/MS analyzes its purity.Molecular weight is 261.
Embodiment 19 water-soluble scavenging agent bromination N-aminoethyl pyridinium salts are used for synthetic N-ethylphenyl-4-methyl benzenesulfonamide
121mg (1mmol) N-ethylaniline is dissolved in the 3ml methylene dichloride under stirring, and slowly adds 237mg (3mmol) pyridine behind adding 382mg (2mmol) the 4-Methyl benzenesulfonyl chlorine.Mixing solutions at room temperature stirs, follow the tracks of reaction process with gas-chromatography, reaction finishes, add 407mg (2mmol) scavenging agent bromination N-aminoethyl pyridinium salt, stirring at room 12 hours adds 10ml ethyl acetate dilute reaction solution and uses 10ml salt water washing 2 times, after organic phase is passed the 0.5cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain 226mgN-ethylphenyl-4-methyl benzenesulfonamide, yield is 82%.It is 97% that GC/MS analyzes its purity.Molecular weight is 275.
Claims (4)
1. the purification process of combined synthesizing amide of solution and sulfamide compound is characterized in that the step of method is as follows:
1) the 1mmol aminated compounds is dissolved in 3～5ml methylene dichloride under stirring, slowly add 2～3mmol triethylamine or pyridine after adding 2～2.5mmol Benzoyl chloride or 4-toluene sulfonyl chloride, mixing solutions at room temperature stirs, and follows the tracks of reaction process with gas-chromatography, and reaction finishes;
2) add the water miscible amino nucleophilicity scavenging agent bromination N-aminoethyl pyridinium salt of 1.2～2.0mmol, stirring at room 6～12 hours, add 10～15ml ethyl acetate dilute reaction solution also with 10～15ml salt water washing 2～3 times, after organic phase is passed 0.5～1cm silicagel column, use anhydrous sodium sulfate drying, concentrate and obtain amides or sulfamide compound.
2. the purification process of combined synthesizing amide of a kind of solution according to claim 1 and sulfamide compound is characterized in that described aminated compounds is aromatic amine compounds, fat amine compound.
3. the purification process of combined synthesizing amide of a kind of solution according to claim 2 and sulfamide compound is characterized in that described aromatic amine compounds is aniline, 4-anisidine, 2-aminotoluene or N-ethylphenyl amine.
4. the purification process of combined synthesizing amide of a kind of solution according to claim 2 and sulfamide compound is characterized in that described fat amine compound is benzylamine, morphine quinoline, amino dodecane, hexahydroaniline or hexahydropyridine.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103265505A (en) * | 2013-05-24 | 2013-08-28 | 浙江工业大学 | Preparation method of N-p-toluenesulfonyl piperidine |
| CN104130165A (en) * | 2014-06-30 | 2014-11-05 | 江苏瑞克医药科技有限公司 | Post-processing method for moclobemide intermediate |
| CN110950783A (en) * | 2019-11-23 | 2020-04-03 | 苏州华道生物药业股份有限公司 | Solid phase synthesis method of N-butyl benzene sulfonamide |
-
2005
- 2005-09-30 CN CNB2005100609792A patent/CN100334067C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103265505A (en) * | 2013-05-24 | 2013-08-28 | 浙江工业大学 | Preparation method of N-p-toluenesulfonyl piperidine |
| CN103265505B (en) * | 2013-05-24 | 2016-03-09 | 浙江工业大学 | A kind of preparation method of N-tosylpiperidine |
| CN104130165A (en) * | 2014-06-30 | 2014-11-05 | 江苏瑞克医药科技有限公司 | Post-processing method for moclobemide intermediate |
| CN104130165B (en) * | 2014-06-30 | 2016-02-03 | 江苏瑞克医药科技有限公司 | A kind of moclobemide intermediate post-treating method |
| CN110950783A (en) * | 2019-11-23 | 2020-04-03 | 苏州华道生物药业股份有限公司 | Solid phase synthesis method of N-butyl benzene sulfonamide |
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