CN105294564B - A kind of synthetic method of 5 amino 1 (2 ethoxy) pyrazoles - Google Patents
A kind of synthetic method of 5 amino 1 (2 ethoxy) pyrazoles Download PDFInfo
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- CN105294564B CN105294564B CN201510902099.9A CN201510902099A CN105294564B CN 105294564 B CN105294564 B CN 105294564B CN 201510902099 A CN201510902099 A CN 201510902099A CN 105294564 B CN105294564 B CN 105294564B
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- pyrazoles
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- ethoxys
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 22
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 title abstract 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 27
- GBHCABUWWQUMAJ-UHFFFAOYSA-N 2-hydrazinoethanol Chemical class NNCCO GBHCABUWWQUMAJ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 12
- 238000010992 reflux Methods 0.000 claims abstract description 11
- JYHSJQNYYLGMEI-UHFFFAOYSA-N 3,3-dimethoxypropanenitrile Chemical compound COC(OC)CC#N JYHSJQNYYLGMEI-UHFFFAOYSA-N 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 3
- 238000002425 crystallisation Methods 0.000 claims abstract description 3
- 230000008025 crystallization Effects 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 150000003217 pyrazoles Chemical class 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000001816 cooling Methods 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 3
- ZINFAXPQMLDEEJ-GFVOIPPFSA-N cefoselis Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CN1C=CC(=N)N1CCO ZINFAXPQMLDEEJ-GFVOIPPFSA-N 0.000 description 2
- 229950001580 cefoselis Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 150000002118 epoxides Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- IHQRJCVJAUKIEP-UHFFFAOYSA-N 2-(5-aminopyrazol-1-yl)ethanol Chemical compound NC1=CC=NN1CCO IHQRJCVJAUKIEP-UHFFFAOYSA-N 0.000 description 1
- PEIBTJDECFEPAF-UHFFFAOYSA-N 2-methoxyprop-2-enenitrile Chemical compound COC(=C)C#N PEIBTJDECFEPAF-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- -1 alkene nitrile Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- KTMGNAIGXYODKQ-UHFFFAOYSA-N ethyl 2-cyano-3-ethoxyprop-2-enoate Chemical compound CCOC=C(C#N)C(=O)OCC KTMGNAIGXYODKQ-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of synthetic method of 5 amino 1 (2 ethoxy) pyrazoles.This method be using water as solvent, β hydrazinoethanols and 3,3 dimethoxypropionitrile heating reflux reactions 2~3 hours；Then sodium hydroxide solution is added dropwise and continues back flow reaction；Salt acid for adjusting pH is added after cooling after completion of the reaction to 5~6；Reaction solution is evaporated, after adding the mixed liquor heating stirring dissolving of toluene and methanol, then the crystallization that cools obtains 5 amino 1 (2 ethoxy) pyrazoles.The synthetic method of the present invention had both avoided decarboxylic reaction present in traditional handicraft, substantially increased yield, and technique is short out, simple to operate, was easy to industrialized production.
Description
Technical field
The present invention relates to a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles, belong to pharmaceutical technology field.
Background technology
Cefoselis is forth generation cephalosporin analog antibiotic, and it is respectively provided with very well to gram-positive bacteria and Gram-negative bacteria
Activity, staphylococcus aureus, Pseudomonas aeruginosa especially to methicillin resistance have good antibacterial activity, in addition to β-
Lactamase is highly stable, lists in states such as Japan, is clinically widely used at present.
5- amino -1- (2- ethoxys) pyrazoles is an important intermediate in Cefoselis building-up process.5- amino -1-
(2- ethoxys) pyrazoles, English name：5-Amino-1- (2-hydroxyethyl) pyrazole, chemical formula：C5H9N3O.Chemistry knot
Structure formula is as follows.
Document《The optimization of synthesis of 5- amino -1- (2- ethoxys) pyrazoles》(Wang Gui armies Hebei chemical industry [J] .2011
07 phase) disclose two kinds of synthetic methods of 5- amino -1- (2- ethoxys) pyrazoles.Synthetic method 1：Using β-hydrazinoethanol and 3-
The step cyclization of methoxy acrylonitrile one generates 5- amino -1- (2- ethoxys)-pyrazoles, is raw material 3- methoxy propyls the shortcomings that this method
The alkene nitrile country does not produce, by import.Synthetic method 2：Using ethyl ethoxy-methylene-cyanoacetate and hydroxyethylhydrazine as raw material, warp
Cyclization, basic hydrolysis, acidifying, decarboxylation four-step reaction obtain product 5- amino -1- (2- ethoxys)-pyrazoles.This method cyclization is given birth to
It is higher into yield during 5- amino -1- (2- ethoxys) -4- formic acid-pyrazoles, but be to continue with down reacting need carry out decarboxylation it is anti-
Should, the yield of this reaction is generally 60% or so, therefore the overall yield of this synthetic route is relatively low.
The content of the invention
Instant invention overcomes above-mentioned the deficiencies in the prior art, there is provided a kind of new 5- amino -1- (2- ethoxys) pyrazoles
Synthetic method, the synthetic method is simple, easily operated, suitable industrialized production.
The technical scheme is that：A kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles, it is characterized in that,
(1) using water as solvent, β-hydrazinoethanol (chemical compounds I) and 3,3- dimethoxypropionitrile (compound ii) are heated to reflux
Reaction 2~3 hours；
(2) and then dropwise addition concentration continues back flow reaction 2~3 hours for 20~50wt% sodium hydroxide solution；
(3) 20~30 DEG C are cooled to after completion of the reaction, add salt acid for adjusting pH to 5~6；Reaction solution is evaporated, adds toluene
(mass ratio of toluene and methanol is 10~13 with the mixed liquor of methanol：1) after heating stirring dissolving, then the crystallization that cools obtains 5- ammonia
Base -1- (2- ethoxys) pyrazoles (compound III).
The synthetic route of the present invention is as follows：
Preferably, the mol ratio of step (1) β-hydrazinoethanol and 3,3- dimethoxypropionitrile is 1.0~1.1：1.
Preferably, the dosage of step (1) water is 5~10ml/g (β-hydrazinoethanol), preferably 6~8ml/g (β-hydrazine
Base ethanol).
Preferably, the concentration of step (2) sodium hydroxide solution is 30wt%, sodium hydroxide and 3,3- dimethoxy third
The mol ratio of nitrile is 1.1~1.2：1.
Preferably, the mass ratio of step (3) toluene and methanol is 11：1.
Preferably, the concentration of step (3) hydrochloric acid is 0.5-3mol/L.
Preferably, the heating stirring of the step (3) is dissolved as being heated to 45-60 DEG C.
The beneficial effects of the invention are as follows：Compared to existing synthetic method, synthetic method of the invention had both avoided traditional work
Decarboxylic reaction present in skill, yield (yield >=90% of product, purity >=99.5%) is substantially increased, and technique is short out,
It is simple to operate, it is easy to industrialized production.
Embodiment
Following examples are the further explanations to the present invention, but the invention is not limited in this.
Embodiment 1
Take 150g β-hydrazinoethanol to add in 2000ml reaction bulbs, then add 1000ml purified waters, add 3,3- bis-
Methoxypropionitrile 222g, heating reflux reaction 2 hours, 30% sodium hydroxide 300g is then slowly added dropwise, continues to be heated to reflux instead
Answer 2 hours, be cooled to 20 DEG C after completion of the reaction, pH to 5 is adjusted with 1mol/L hydrochloric acid.Evaporated under reduced pressure reaction solution, then adds first
Benzene 440g, methanol 40g, are heated to 50 DEG C of stirring and dissolvings 30 minutes, then cool to 10 DEG C, stirring and crystallizing 2 hours, filter, use
10g methanol washs filter cake, and solid 231.2g, yield 94.2%, purity 99.53% are obtained after drying.
Embodiment 2
Take 75g β-hydrazinoethanol to add in 1000ml reaction bulbs, then add 500ml purified waters, add 3,3- diformazans
Epoxide propionitrile 110g, heating reflux reaction 2 hours, 30% sodium hydroxide 150g is then slowly added dropwise, continues heating reflux reaction 2
Hour, 25 DEG C are cooled to after completion of the reaction, are adjusted PH to 6 with 1mol/L hydrochloric acid, evaporated under reduced pressure reaction solution, are then added toluene
220g, methanol 20g, are heated to 52 DEG C of stirring and dissolvings 30 minutes, then cool to 10 DEG C, stirring and crystallizing 2 hours, filtering, use 5g
Methanol washs filter cake, and solid 115.4g, yield 94.6%, purity 99.57% are obtained after drying.
Embodiment 3
Take 150g β-hydrazinoethanol to add in 2000ml reaction bulbs, then add 1000ml purified waters, add 3,3- bis-
Methoxypropionitrile 220g, heating reflux reaction 2.5 hours, 30% sodium hydroxide 305g is then slowly added dropwise, continues to be heated to reflux
Reaction 2.5 hours, is cooled to 22 DEG C after completion of the reaction, and pH to 5 is adjusted with 1.5mol/L hydrochloric acid.Evaporated under reduced pressure reaction solution, then
Toluene 420g, methanol 40g are added, is heated to 50 DEG C of stirring and dissolvings 30 minutes, then cools to 10 DEG C, stirring and crystallizing 2 hours, mistake
Filter, filter cake is washed with 10g methanol, and solid 231.7g, yield 94.8%, purity 99.52% are obtained after drying.
Embodiment 4
Take 75g β-hydrazinoethanol to add in 1000ml reaction bulbs, then add 550ml purified waters, add 3,3- diformazans
Epoxide propionitrile 111g, heating reflux reaction 2.5 hours, 30% sodium hydroxide 148g is then slowly added dropwise, continues to be heated to reflux instead
Answer 2.5 hours, be cooled to 25 DEG C after completion of the reaction, adjust pH to 6 with 1mol/L hydrochloric acid, evaporated under reduced pressure reaction solution, then add first
Benzene 250g, methanol 20g, are heated to 52 DEG C of stirring and dissolvings 30 minutes, then cool to 10 DEG C, stirring and crystallizing 2 hours, filter, use
5g methanol washs filter cake, and solid 116.2g, yield 94.7%, purity 99.61% are obtained after drying.
Claims (9)
1. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles, it is characterized in that,
(1) using water as solvent, β-hydrazinoethanol and 3,3- dimethoxypropionitrile heating reflux reaction 2~3 hours；
(2) and then dropwise addition concentration continues back flow reaction 2~3 hours for 20~50wt% sodium hydroxide solution；
(3) 20~30 DEG C are cooled to after completion of the reaction, add salt acid for adjusting pH to 5~6；Reaction solution is evaporated, adds toluene and first
After the mixed liquor heating stirring dissolving of alcohol, then the crystallization that cools obtains 5- amino -1- (2- ethoxys) pyrazoles；The toluene and methanol
Mass ratio be 10~13：1.
2. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as claimed in claim 1, it is characterized in that, the step
Suddenly the mol ratio of (1) β-hydrazinoethanol and 3,3- dimethoxypropionitrile is 1.0~1.1：1.
3. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as claimed in claim 1, it is characterized in that, the step
Suddenly (1) uses gauge with β-hydrazinoethanol, and the dosage of water is 5~10ml/g.
4. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as claimed in claim 3, it is characterized in that, the step
Suddenly (1) uses gauge with β-hydrazinoethanol, and the dosage of water is 6~8ml/g.
5. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as claimed in claim 1, it is characterized in that, the step
Suddenly the concentration of (2) sodium hydroxide solution is 30wt%.
6. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as claimed in claim 1, it is characterized in that, the step
Suddenly the mol ratio of (2) sodium hydroxide and 3,3- dimethoxypropionitrile is 1.1~1.2：1.
7. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as described in any one in claim 1-6, it is special
Sign is that the mass ratio of toluene and methanol is 11 in the step (3)：1.
8. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as described in any one in claim 1-6, it is special
Sign is that the concentration of step (3) hydrochloric acid is 0.5-3mol/L.
9. a kind of synthetic method of 5- amino -1- (2- ethoxys) pyrazoles as described in any one in claim 1-6, it is special
Sign is that the heating stirring of the step (3) is dissolved as being heated to 45-60 DEG C.
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| CN113698348A (en) * | 2021-09-07 | 2021-11-26 | 安徽华甬新材料股份有限公司 | Preparation method of 4, 5-diamino-1- (2-hydroxyethyl) pyrazole sulfate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1342716A2 (en) * | 2002-02-22 | 2003-09-10 | Eastman Chemical Company | Preparation of 4,5-diamino-1-(2'-hydroxyethyl)-pyradazole and acid addition salts thereof |
| CN101367764A (en) * | 2007-08-17 | 2009-02-18 | 长沙理工大学 | A new synthesis process of 5-amino-1-hydroxyethylpyrazole and its analogs |
| CN103819405A (en) * | 2012-11-19 | 2014-05-28 | 王香善 | Method for preparing N-(1-(2-formyloxy ethyl)-1H-pyrazole-5-base) formamide |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0662578B2 (en) * | 1987-09-29 | 1994-08-17 | 宇部興産株式会社 | Process for producing 1-substituted 5-aminopyrazole |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1342716A2 (en) * | 2002-02-22 | 2003-09-10 | Eastman Chemical Company | Preparation of 4,5-diamino-1-(2'-hydroxyethyl)-pyradazole and acid addition salts thereof |
| CN101367764A (en) * | 2007-08-17 | 2009-02-18 | 长沙理工大学 | A new synthesis process of 5-amino-1-hydroxyethylpyrazole and its analogs |
| CN103819405A (en) * | 2012-11-19 | 2014-05-28 | 王香善 | Method for preparing N-(1-(2-formyloxy ethyl)-1H-pyrazole-5-base) formamide |
Non-Patent Citations (3)
| Title |
|---|
| 5- 氨基-1-羟乙基吡唑的合成研究;黄朋勉,等;《精细化工中间体》;20080831;第38卷(第4期);28-30 * |
| 中间体-（2-羟乙基）-3-氨基-4-羧基吡唑的合成研究;郭俊晶，等;《中国药学杂志》;20090531;第44卷(第10期);796-798 * |
| 以氰基乙醛为中间体合成吡唑类化合物;姚鹏;《化学试剂》;20130630;第35卷(第6期);570-572，尤其路线图，1.2.2节 * |
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