CN107721941A - A kind of preparation method of the methyl-isoxazole of 3 amino 5 - Google Patents
A kind of preparation method of the methyl-isoxazole of 3 amino 5 Download PDFInfo
- Publication number
- CN107721941A CN107721941A CN201710939463.8A CN201710939463A CN107721941A CN 107721941 A CN107721941 A CN 107721941A CN 201710939463 A CN201710939463 A CN 201710939463A CN 107721941 A CN107721941 A CN 107721941A
- Authority
- CN
- China
- Prior art keywords
- methyl
- amino
- isoxazoles
- acetonitrile
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
- C07D261/14—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses a kind of preparation method of the methyl-isoxazole of 3 amino 5, is completed by three steps, belongs to technical field of organic chemistry.From the raw acetic acid ethyl ester being easy to get with acetonitrile in the presence of metal base, be initially formed acetyl acetonitrile, then again with tolysulfonyl hydrazine reaction into hydrazone, then ring closure reaction obtains the methyl-isoxazole of 3 amino 5 in the basic conditions with azanol.Raw material is all relatively common in reaction, avoids chloroform or carbon tetrachloride in conventional method, and the similar isomers generation of product is not detected by course of reaction.
Description
Technical field：
The present invention relates to a kind of preparation method of 3- amino -5- methyl-isoxazoles, belong to technical field of organic synthesis.
Background technology：
3- amino -5- methyl-isoxazoles, English name 3-Amino-5-Methylisoxazole, white crystal, CAS：
1072-67-9.Alcohol, ether are dissolved in, is volatilized with vapor.Medicine intermediate.For producing sulfonamides, especially anti-infectives
Radonil.Radonil, a kind of broad-spectrum antibiotic, belong to one-level anti-microbial type, suppurated for urinary tract infections, respiratory tract infection, skin
Sexuality dye, tonsillitis；Shared with synergist, its antibacterial efficacy is remarkably reinforced, and can increase several times to tens times.It is clinically used for
Tonsillitis, acute bronchitis, pulmonary infection, urinary tract infections, skin pyogenic infection, bacillary dysentery and typhoid fever etc..
The synthetic method of the compound mainly includes following several at present：
The first, using 5- methyl-isoxazole -3- formamides, chlorination generates N- chloroamides in aqueous sodium hypochlorite solution
Sodium, then de- group of generation 3- amino -5- methylisoxazole of normal pressure or pressurized, heated, takes off in 104 DEG C of normal pressures and dials, yield 83%；150
DEG C pressurization is de- dials, then yield is 95%.Dialled during country's trial-production using normal pressure is de-, yield only 67%.In above-mentioned technique, from chloroform
Extraction.Chloroform consumption is big, and the rate of recovery is low, easily emulsifies during layering.
Second, with hydroxylamine hydrochloride and 2- methyl -2- acetonitrile-bases -1,3- dioxolane be raw material prepare 5- methyl -
3- An isoxazoles.Hydroxylamine hydrochloride is dissolved in ammoniacal liquor, adds the 60 DEG C of reactions 6 of 2- methyl -2- acetonitrile-bases -1,3- dioxolane
Hour, 2- methyl -2- second amidoxime group -1,3- dioxolane is obtained, adds chloroform dissolving, adds concentrated hydrochloric acid backflow,
Adjust pH value to be more than 13, chloroform extraction, be evaporated to obtain 5- methyl -3- amido isoxazoles.
The third, substituted acetyl acetonitrile and hydroxylamine hydrochloride are reacted under weak basic condition and obtain amino oxime and accessory substance
The mixture of 5- amino -3- substituted isoxazoles compounds, then removes the accessory substance, amino oxime exists using carbon tetrachloride extraction method
Ring-closure reaction occurs in the presence of weak acid, finally obtains 5- substitutions -3- amino-isoxazole compound.
In the above method, hypertoxic solvent chloroform or carbon tetrachloride are all inevitably used, or while in the presence of needs
Strong oxdiative condition, or the separation of isomers be present, for pharmaceutical field, single miscellaneous amount needs strict control, especially
The very similar isomers of property especially has a negative impact.
The content of the invention：
To overcome disadvantage mentioned above, it is an object of the present invention to provide a kind of preparation method of 3- amino -5- methyl-isoxazoles, passes through
Three steps are completed.From the raw acetic acid ethyl ester being easy to get with acetonitrile in the presence of metal base, be initially formed acetyl acetonitrile, Ran Houzai
With tolysulfonyl hydrazine reaction into hydrazone, then ring closure reaction obtains 3- amino -5- methyl-isoxazoles in the basic conditions with azanol.
A kind of preparation method of 3- amino -5- methyl-isoxazoles, is obtained, the technical scheme of use after three-step reaction
For：
The first step, acetonitrile react generation anion in metal base, are then reacted with ethyl acetate or methyl acetate, obtain second
Acyl acetonitrile.
Second step, acetyl acetonitrile add alcoholic solvent and unifor, corresponding hydrazone are obtained after back flow reaction.
3rd step, after hydroxylamine hydrochloride addition potassium carbonate is dissociated, the hydrazone that step obtains is added, heat up ring closure reaction, obtains
To 3- amino -5- methyl-isoxazoles.
Reaction scheme is as follows：
Further, in the first step, metal base selects NaH, n-BuLi or LDA, and addition is worked as the 1.1-1.4 of acetonitrile
Amount, it is 1 equivalent of ethyl acetate or methyl acetate.
Further, in second step, alcoholic solvent is selected from methanol or ethanol.Acetyl acetonitrile is with unifor equivalent proportion
1：0.95-1, the hydrazone obtained after reaction are white crystalline solid.
Further, in the 3rd step, potassium carbonate addition is the 2.2-4 equivalents of hydroxylamine hydrochloride.After free end, second is added
Glycol dimethyl ether, diethoxymethane, tetrahydrofuran, 2- methyltetrahydrofurans or toluene, carry out ring closure reaction.
Further, the optimal reaction temperature of the 3rd step ring closure reaction is 65-90 DEG C, i.e., solvent is micro- is back to counterflow condition
Lower progress, when temperature reduces by less than 40 DEG C, reaction needs to complete more than 3 days, reacts do not occur at room temperature.Done using toluene
Solvent, reacting under counterflow condition can complete in 1 hour.In view of the convenience of extracting and demixing, the preferred diethoxy of reaction dissolvent
Methylmethane or 2- methyltetrahydrofurans.
Beneficial effects of the present invention：
(1) raw material is all relatively common in this reaction, and less expensive, and purchase transport and use are all very convenient.
(2) hydrazine make use of to generate cation in the basic conditions in course of reaction, the attack for being advantageous to hydroxyl reaches
Quick cyclization；
(3) chloroform or carbon tetrachloride in conventional method are instead of using diethoxymethane and 2- methyltetrahydrofurans,
Reduce labor protection.
(4) the similar isomers generation of product is not detected by course of reaction using HPLC-MS.
Embodiment
Embodiment 1
The first step, in 500mL reaction bulbs, sodium hydride (12.0g, 0.3mol, 60%) is added and is dissolved in 120mL tetrahydrofurans
Acetonitrile (10.3g, 0.25mol) solution in, then add ethyl acetate (26.4g, 0.3mol), be heated to reflux 4 hours, be down to
Room temperature, frozen water are quenched, and 2N HCl adjust pH value 5-6, and ethyl acetate extracts, and after organic layer anhydrous sodium sulfate drying, concentrates out solvent
Obtain acetyl acetonitrile 18.9g, GC purity 96%, yield 91%.
Second step, in 1L reaction bulbs, upper step products obtained therefrom acetyl acetonitrile (18.9g, 0.23mol) is dissolved in 600mL methanol
In, unifor (40.2g, 0.22mol) is added, is heated to reflux 2 hours, cool crystallization, filters to obtain white crystalline solid
Hydrazone 50.3g, HPLC purity 99%, yield 88%.
3rd step, in 500mL reaction bulbs, add hydroxylamine hydrochloride (16.7g, 0.24mol), potassium carbonate (99.5g,
0.72mol) with 40mL water, it is stirred at room temperature 0.5 hour, hydrazone obtained by addition tetrahydrofuran (360mL) and upper step (50.3g,
0.20mol), 65 DEG C are warming up to, is incubated 2 hours, cooling, concentrated hydrochloric acid is added dropwise and adjusts pH value 1, stirs 1 hour, layering, discards organic
Layer, the water layer molten tune pH value 10-12 of 20% sodium hydroxide, a large amount of precipitations of precipitation, filtering, light yellow crystal 3- ammonia is obtained after drying
Base -5- methyl-isoxazoles 15.5g, HPLC purity 98.8%, yield 79%.
Embodiment 2
The first step, in 500mL reaction bulbs, sodium hydride (14g, 0.35mol, 60%) is added and is dissolved in 120mL tetrahydrofurans
Acetonitrile (10.3g, 0.25mol) solution in, then add methyl acetate (25.9g, 0.35mol), be heated to reflux 4 hours, drop
To room temperature, frozen water is quenched, and 2N HCl adjust pH value 5-6, and ethyl acetate extracts, and after organic layer anhydrous sodium sulfate drying, concentrates out molten
Agent obtains acetyl acetonitrile 19.1g, GC purity 96%, yield 92%.
Second step, in 1L reaction bulbs, upper step products obtained therefrom acetyl acetonitrile (19.1g, 0.23mol) is dissolved in 600mL ethanol
In, unifor (42.8g, 0.23mol) is added, is heated to reflux 2 hours, cool crystallization, filters to obtain white crystalline solid
Hydrazone 52.0g, HPLC purity 99%, yield 90%.
3rd step, in 500mL reaction bulbs, add hydroxylamine hydrochloride (17.3g, 0.25mol), potassium carbonate (75.4g,
0.55mol) with 40mL water, it is stirred at room temperature 0.5 hour, adds hydrazone obtained by 2- methyltetrahydrofurans (360mL) and upper step
(0.21mol), 80 DEG C are warming up to, are incubated 2 hours, cooling, concentrated hydrochloric acid is added dropwise and adjusts pH value 1, stirs 1 hour, layering, discards organic
Layer, the water layer molten tune pH value 10-12 of 20% sodium hydroxide, a large amount of precipitations of precipitation, filtering, light yellow crystal 3- ammonia is obtained after drying
Base -5- methyl-isoxazoles 15.8g, HPLC purity 98.8%, yield 78%.
Embodiment 3
The first step, in 500mL reaction bulbs, by diisopropylamine (35.4g, 0.35mol) tetrahydrofuran (140mL) solution body
System is cooled to less than -30 DEG C, the lower hexane solution (140mL, 0.35mol, 2.5M) that n-BuLi is added dropwise of nitrogen protection, is added dropwise
Finish, be stirred at room temperature 30 minutes, be cooled at -78 DEG C, be added dropwise ethyl acetate (30.8g, 0.35mol) acetonitrile (10.3g,
0.25mol) solution, it is added dropwise, is stirred at room temperature 2 hours, reaction terminates rear 2N HCl and tune pH value 5-6, ethyl acetate extraction is quenched
Take, after organic layer anhydrous sodium sulfate drying, concentrate out solvent and obtain colorless oil acetyl acetonitrile 18.1g, GC purity 98%, yield
87%.
Second step, in 1L reaction bulbs, upper step products obtained therefrom acetyl acetonitrile 18.1g is dissolved in 600mL methanol, added to first
Benzene sulfonyl hydrazide (40.5g, 0.22mol), it is heated to reflux 2 hours, cool crystallization, filters to obtain white crystalline solid hydrazone 48.1g, HPLC
Purity 99%, yield 88%.
3rd step, in 500mL reaction bulbs, add hydroxylamine hydrochloride (16.0g, 0.23mol), potassium carbonate (127.1g,
0.92mol) with 40mL water, it is stirred at room temperature 0.5 hour, hydrazone obtained by addition diethoxymethane (360mL) and upper step (48.1g,
0.19mol), 85 DEG C are warming up to, is incubated 2 hours, cooling, concentrated hydrochloric acid is added dropwise and adjusts pH value 1, stirs 1 hour, layering, discards organic
Layer, the water layer molten tune pH value 10-12 of 20% sodium hydroxide, a large amount of precipitations of precipitation, filtering, light yellow crystal 3- ammonia is obtained after drying
Base -5- methyl-isoxazoles 15.0g, HPLC purity 98.7%, yield 80%.
Embodiment 4
The first step, in 500mL reaction bulbs, by diisopropylamine (27.8g, 0.28mol) tetrahydrofuran (100mL) solution body
System is cooled to less than -30 DEG C, the lower hexane solution (110mL, 0.28mol, 2.5M) that n-BuLi is added dropwise of nitrogen protection, is added dropwise
Finish, be stirred at room temperature 30 minutes, be cooled at -78 DEG C, be added dropwise methyl acetate (20.4g, 0.28mol) acetonitrile (10.3g,
0.25mol) solution, it is added dropwise, is stirred at room temperature 2 hours, reaction terminates rear 2N HCl and tune pH value 5-6, ethyl acetate extraction is quenched
Take, after organic layer anhydrous sodium sulfate drying, concentrate out solvent and obtain colorless oil acetyl acetonitrile 17.7g, GC purity 98%, yield
85%.
Second step, in 1L reaction bulbs, upper step products obtained therefrom acetyl acetonitrile (17.7g, 0.21mol) is dissolved in 600mL ethanol
In, unifor (39.6g, 0.21mol) is added, is heated to reflux 2 hours, cool crystallization, filters to obtain white crystalline solid
Hydrazone 48.1g, HPLC purity 99%, yield 90%.
3rd step, in 500mL reaction bulbs, add hydroxylamine hydrochloride (16.0g, 0.23mol), potassium carbonate (95.2g,
0.69mol) with 40mL water, it is stirred at room temperature 0.5 hour, hydrazone obtained by addition glycol dimethyl ether (360mL) and upper step (48.1g,
0.19mol), 80 DEG C are warming up to, is incubated 2 hours, cooling, concentrated hydrochloric acid is added dropwise and adjusts pH value 1, stirs 1 hour, layering, discards organic
Layer, the water layer molten tune pH value 10-12 of 20% sodium hydroxide, a large amount of precipitations of precipitation, filtering, light yellow crystal 3- ammonia is obtained after drying
Base -5- methyl-isoxazoles 14.6g, HPLC purity 98.8%, yield 78%.
Embodiment 5
The first step, in 500mL reaction bulbs, acetonitrile (10.3g, 0.25mol) tetrahydrofuran (50mL) solution system is dropped
Temperature the lower hexane solution (140mL, 0.35mol, 2.5M) that n-BuLi is added dropwise of nitrogen protection, is added dropwise, protected to -78 DEG C
Tetrahydrofuran (60mL) Solutions Solution of ethyl acetate (30.8g, 0.35mol) is added dropwise in temperature stirring at 30 minutes, -78 DEG C, be added dropwise
Finish, be stirred at room temperature 2 hours, reaction terminates rear 2N HCl and tune pH value 5-6, ethyl acetate extraction, organic layer anhydrous slufuric acid is quenched
After sodium is dried, concentrate out solvent and obtain colorless oil acetyl acetonitrile 17.6g, GC purity 98%, yield 85%.
Second step, in 1L reaction bulbs, upper step products obtained therefrom acetyl acetonitrile (17.6g, 0.21mol) is dissolved in 600mL ethanol
In, unifor (37.6g, 0.20mol) is added, is heated to reflux 2 hours, cool crystallization, filters to obtain white crystalline solid
Hydrazone 48.0g, HPLC purity 99%, yield 90%.
3rd step, in 500mL reaction bulbs, add hydroxylamine hydrochloride (15.9g, 0.23mol), potassium carbonate (95.0g,
0.69mol) with 40mL water, it is stirred at room temperature 0.5 hour, adds hydrazone (48.0g, 0.19mol) obtained by toluene (360mL) and upper step,
90 DEG C are warming up to, is incubated 2 hours, cooling, concentrated hydrochloric acid is added dropwise and adjusts pH value 1, stirs 1 hour, layering discards organic layer, and water layer is used
The molten tune pH value 10-12 of 20% sodium hydroxide, a large amount of precipitations of precipitation, filtering, it is different to obtain light yellow crystal 3- amino -5- methyl after drying
Oxazole 15.0g, HPLC purity 98.9%, yield 80%.
Embodiment 6
The first step, in 500mL reaction bulbs, acetonitrile (10.3g, 0.25mol) tetrahydrofuran (50mL) solution system is dropped
Temperature the lower hexane solution (110mL, 0.28mol, 2.5M) that n-BuLi is added dropwise of nitrogen protection, is added dropwise, protected to -78 DEG C
Tetrahydrofuran (40mL) Solutions Solution of methyl acetate (20.4g, 0.28mol) is added dropwise in temperature stirring at 30 minutes, -78 DEG C, be added dropwise
Finish, be stirred at room temperature 2 hours, reaction terminates rear 2N HCl and tune pH value 5-6, ethyl acetate extraction, organic layer anhydrous slufuric acid is quenched
After sodium is dried, concentrate out solvent and obtain acetyl acetonitrile 17.4g, GC purity 97%, yield 84%.
Second step, in 1L reaction bulbs, upper step products obtained therefrom acetyl acetonitrile (17.4g, 0.21mol) is dissolved in 600mL methanol
In, unifor (37.2g, 0.20mol) is added, is heated to reflux 2 hours, cool crystallization, filters to obtain white crystalline solid
Hydrazone 46.4g, HPLC purity 99%, yield 88%.
3rd step, in 500mL reaction bulbs, add hydroxylamine hydrochloride (15.4g, 0.22mol) add potassium carbonate (76.0g,
0.55mol) with 40mL water, it is stirred at room temperature 0.5 hour, hydrazone obtained by addition 2- methyltetrahydrofurans (360mL) and upper step (46.4g,
0.18mol), 80 DEG C are warming up to, is incubated 2 hours, cooling, concentrated hydrochloric acid is added dropwise and adjusts pH value 1, stirs 1 hour, layering, discards organic
Layer, the water layer molten tune pH value 10-12 of 20% sodium hydroxide, a large amount of precipitations of precipitation, filtering, light yellow crystal 3- ammonia is obtained after drying
Base -5- methyl-isoxazoles 14.1g, HPLC purity 98.7%, yield 78%.
The general principle and principal character and advantages of the present invention of the present invention has been shown and described above.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the simply explanation described in above-described embodiment and specification is originally
The principle of invention, without departing from the spirit and scope of the present invention, various changes and modifications of the present invention are possible, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent thereof.
Claims (8)
- A kind of 1. preparation method of 3- amino -5- methyl-isoxazoles, it is characterised in that：Ethyl acetate exists with acetonitrile in metal base Lower generation acetyl acetonitrile, then again with tolysulfonyl hydrazine reaction into hydrazone, then cyclization is anti-in the basic conditions with hydroxylamine hydrochloride 3- amino -5- methyl-isoxazoles should be obtained.
- 2. according to a kind of preparation method of 3- amino -5- methyl-isoxazoles in claim 1, it is characterised in that including following step Suddenly：The first step, acetonitrile react generation anion in metal base, are then reacted with ethyl acetate or methyl acetate, obtain acetyl second Nitrile；Second step, acetyl acetonitrile add alcoholic solvent and unifor, corresponding hydrazone are obtained after back flow reaction；3rd step, hydroxylamine hydrochloride addition potassium carbonate is dissociated, then adds the hydrazone for walking to obtain, heat up ring closure reaction, obtains 3- Amino -5- methyl-isoxazoles.
- 3. a kind of preparation method of 3- amino -5- methyl-isoxazoles according to claim 1 or 2, it is characterized in that：Metal base From NaH, n-BuLi or LDA, addition is the 1.1-1.4 equivalents of acetonitrile, is 1 equivalent of ethyl acetate or methyl acetate.
- 4. a kind of preparation method of 3- amino -5- methyl-isoxazoles according to claim 2, it is characterized in that：In second step, Alcoholic solvent is selected from methanol or ethanol.
- 5. a kind of preparation method of 3- amino -5- methyl-isoxazoles according to claim 1 or 2, it is characterized in that：The second Acyl acetonitrile is 1 with unifor mol ratio：0.95-1.
- 6. a kind of preparation method of 3- amino -5- methyl-isoxazoles according to claim 2, it is characterized in that：The carbonic acid Potassium addition is the 2.2-4 equivalents of hydroxylamine hydrochloride.
- 7. a kind of preparation method of 3- amino -5- methyl-isoxazoles according to claim 2, it is characterized in that：Described 3rd In step, reaction dissolvent is selected from glycol dimethyl ether, diethoxymethane, tetrahydrofuran or 2- methyltetrahydrofurans.
- 8. a kind of preparation method of 3- amino -5- methyl-isoxazoles according to claim 2, it is characterized in that：Described 3rd In step, reaction temperature is 65-90 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710939463.8A CN107721941B (en) | 2017-10-10 | 2017-10-10 | Preparation method of 3-amino-5-methyl isoxazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710939463.8A CN107721941B (en) | 2017-10-10 | 2017-10-10 | Preparation method of 3-amino-5-methyl isoxazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107721941A true CN107721941A (en) | 2018-02-23 |
| CN107721941B CN107721941B (en) | 2020-05-22 |
Family
ID=61210182
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710939463.8A Active CN107721941B (en) | 2017-10-10 | 2017-10-10 | Preparation method of 3-amino-5-methyl isoxazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107721941B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022206010A1 (en) * | 2021-03-29 | 2022-10-06 | 苏州大学 | Simple preparation method for isoxazolines |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4256898A (en) * | 1978-05-15 | 1981-03-17 | The Upjohn Company | α(substituted) Amino-3-substituted-2-isoxazoline-5-acetic acids (esters) |
| JPH04275277A (en) * | 1991-03-01 | 1992-09-30 | Sumitomo Chem Co Ltd | Production of 5-aminopyrazoles |
| CN1402715A (en) * | 1999-11-30 | 2003-03-12 | 武田药品工业株式会社 | Processes for production of oxadiazoline derivs. |
| CN1642918A (en) * | 2002-04-05 | 2005-07-20 | 卡地拉健康护理有限公司 | Novel hererocyclic compound and preparation thereof and medicine composition containing same and use thereof in medicine |
| CN103435592A (en) * | 2013-08-12 | 2013-12-11 | 南京欧信医药技术有限公司 | 2-((4R,6S)-6-formaldehyde-2,2-dimethyl-1,3 dioxane-4-base)-methyl acetate preparation method |
| CN103562178A (en) * | 2011-06-03 | 2014-02-05 | 住友化学株式会社 | Method of manufacturing isoxazoline compound |
| CN104592144A (en) * | 2015-01-12 | 2015-05-06 | 上海鼎雅药物化学科技有限公司 | New method for preparing oxazole derivative |
| WO2015196071A1 (en) * | 2014-06-19 | 2015-12-23 | Proteostasis Therapeutics, Inc. | Compounds, compositions and methods of increasing cftr activity |
-
2017
- 2017-10-10 CN CN201710939463.8A patent/CN107721941B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4256898A (en) * | 1978-05-15 | 1981-03-17 | The Upjohn Company | α(substituted) Amino-3-substituted-2-isoxazoline-5-acetic acids (esters) |
| JPH04275277A (en) * | 1991-03-01 | 1992-09-30 | Sumitomo Chem Co Ltd | Production of 5-aminopyrazoles |
| CN1402715A (en) * | 1999-11-30 | 2003-03-12 | 武田药品工业株式会社 | Processes for production of oxadiazoline derivs. |
| CN1642918A (en) * | 2002-04-05 | 2005-07-20 | 卡地拉健康护理有限公司 | Novel hererocyclic compound and preparation thereof and medicine composition containing same and use thereof in medicine |
| CN103562178A (en) * | 2011-06-03 | 2014-02-05 | 住友化学株式会社 | Method of manufacturing isoxazoline compound |
| CN103435592A (en) * | 2013-08-12 | 2013-12-11 | 南京欧信医药技术有限公司 | 2-((4R,6S)-6-formaldehyde-2,2-dimethyl-1,3 dioxane-4-base)-methyl acetate preparation method |
| WO2015196071A1 (en) * | 2014-06-19 | 2015-12-23 | Proteostasis Therapeutics, Inc. | Compounds, compositions and methods of increasing cftr activity |
| CN104592144A (en) * | 2015-01-12 | 2015-05-06 | 上海鼎雅药物化学科技有限公司 | New method for preparing oxazole derivative |
Non-Patent Citations (5)
| Title |
|---|
| GUO-BO LI等: "Drug Discovery against Psoriasis:Identfication of a New Potent FMS-like Tyrosine Kinase 3(FLT3)Inhibitor,1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-florophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea,That Showed Potent Activity in a Psoriatic Animal Model", 《J. MED. CHEM.》 * |
| ZHIMIN CHEN等: "The synthesis and properties of highly organosoluble metal(II) complexes with hydrazone ligands derived from pivaloylacetonitrile", 《DYES AND PIGMENTS》 * |
| 周星雷等: "3-氨甲酰基-和3-氨基-5-甲基异噁唑的合成工艺研究", 《中国医药工业杂志》 * |
| 唐晖等: "5-甲基-4-异噁唑甲酰肼的合成研究", 《科学技术与工程》 * |
| 孙明娜等: "1H-吲唑的合成研究进展", 《化学试剂》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022206010A1 (en) * | 2021-03-29 | 2022-10-06 | 苏州大学 | Simple preparation method for isoxazolines |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107721941B (en) | 2020-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2954276C (en) | Process for the preparation of 4-alkoxy-3-hydroxypicolinic acids | |
| CN107445909B (en) | Preparation method of prothioconazole intermediate | |
| CN109438405A (en) | A kind of synthetic method of 3- (benzyloxy) -4- oxo -4H- pyrans -2- carboxylic acid | |
| US11958858B2 (en) | Method for preparation of Asenapine | |
| CN105452256A (en) | Method for preparing a pyripyropene compound | |
| CN110878084A (en) | Preparation method of nicosulfuron original drug | |
| CN107721941A (en) | A kind of preparation method of the methyl-isoxazole of 3 amino 5 | |
| CN103554031B (en) | Preparation method of azilsartan intermediate | |
| US20180346443A1 (en) | Preparation Method Of Intermediate For Oxazolidinone Derivative | |
| CN103896858B (en) | The preparation technology of cytosine | |
| CN105218329A (en) | Clean analogue intermediate of a kind of row and preparation method thereof | |
| WO2011113788A1 (en) | Process for purifying 3-difluoromethyl-1-methyl-1h-pyrazole-4-carboxylic acid | |
| CN107118128B (en) | Preparation method of 3, 4-dihydroxy benzonitrile | |
| CN107879992A (en) | A kind of preparation method of (base of 1 methyl 1H [1,2,4] triazole 3) methanol | |
| CN106146486A (en) | A kind of method preparing high-purity high-yield Lurasidone | |
| CN107602497B (en) | Preparation method of 3-amino-5-alkylisoxazole | |
| CN104725349A (en) | Polycrystalline A-type crystal of alogliptin polycrystalline, preparation method and production purpose thereof | |
| CN106083631B (en) | A kind of preparation method of equal amido phenenyl acid | |
| WO2020125581A1 (en) | Amide derivatives and preparation method for intermediates thereof | |
| CN105061227A (en) | Environment-friendly ritodrine hydrochloride production method | |
| CN105924400B (en) | The preparation method of Azilsartan impurity A and B | |
| CN104230909B (en) | A kind of preparation method of Azilsartan | |
| CN104817482A (en) | 2-substituted pyrrolidine compound, preparation method and application thereof in preparation of vildagliptin | |
| CN107739343A (en) | A kind of environment-friendly type technique for producing Quizalotop-ethyl | |
| US20220204455A1 (en) | A process for the synthesis of lofexidine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Lu Dianyun Inventor after: Qi Wei Jun Inventor after: Xiao Haiwang Inventor after: Cai Weibing Inventor before: Qi Wei Jun Inventor before: Xiao Haiwang Inventor before: Cai Weibing |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |