CN108659004A - The preparation method of Oxiracetam isomers - Google Patents
The preparation method of Oxiracetam isomers Download PDFInfo
- Publication number
- CN108659004A CN108659004A CN201810764944.4A CN201810764944A CN108659004A CN 108659004 A CN108659004 A CN 108659004A CN 201810764944 A CN201810764944 A CN 201810764944A CN 108659004 A CN108659004 A CN 108659004A
- Authority
- CN
- China
- Prior art keywords
- oxiracetam
- type
- acid lactone
- salt
- reaction
- 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
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
Abstract
The invention belongs to pharmaceutical synthesis fields, and in particular to the preparation method of Oxiracetam isomers.(S) Oxiracetam, (R) Oxiracetam of the present invention is prepared by following steps：1) dehydration generates Oxiracetam lactone in Oxiracetam acid molecule；2) lactone reacts generation (1R, 5R), (1S, 5R), (1R, 5S), (1S, 5S) type Oxiracetam acid lactone salt with 10 camphorsulfonic acids of D (+)；3) (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt reacts generation (R) Oxiracetam, (1R with ammonia, 5S), (1S, 5S) type Oxiracetam acid lactone salt reacts generation (S) Oxiracetam with ammonium hydroxide.Method provided by the invention can prepare (S) Oxiracetam and (R) Oxiracetam, do not waste material, have the advantages that easy to operate, product yield high (up to 60%), product purity are high (99.8% or more), is suitable for industrialized large-scaled production.
Description
Technical field
The invention belongs to pharmaceutical synthesis fields, and in particular to Oxiracetam isomers (S)-Oxiracetam, (R)-Aura west
Smooth preparation method.
Background technology
The present invention relates to a kind of synthesis of Esomeprazole (i.e. Oxiracetam).Oxiracetam
Molecular formula is C6H10N2O3, it is a kind of hydroxy-amino-butyric acid cyclic derivatives of synthesis, structural formula is as follows：
Oxiracetam is that one kind acting on the cholinergic nootropic of reticular formation of brain stem, is used for cerebral injury and caused nerve
Afunction, memory and the treatment of disturbance of intelligence, wide market.
There are some researches prove the isomers of Oxiracetam (S)-Oxiracetams to play more your writing than (R)-Oxiracetam
With.
106146379 B of patent of invention CN disclose a kind of synthetic method of (S)-Oxiracetam, include the following steps：
(1) using S-4- amino -3-hydroxybutyrate as starting material, esterification is carried out with alcohol, obtains intermediate compound I；(2) by intermediate compound I
Condensation reaction is carried out with halogenated acetic acids ester, obtains intermediate II；(3) intermediate II progress ring closure reaction is obtained into intermediate III；
(4) intermediate III is subjected to ammonolysis reaction, obtains target product (S)-Oxiracetam.Invention (the S)-Oxiracetam yield only has
20%, and synthesis step is long, complicated for operation, product cost is higher, is not appropriate for industrialized production.
Being used to prepare Oxiracetam as raw material using Oxiracetam acid has the advantages that reaction step is short.Patent of invention
CN106496989A discloses a kind of technique preparing Oxiracetam by Oxiracetam acid, Oxiracetam acid and compound R-CH2-
OH reacts, and generates the compound with structure shown in formula (A)：
The invention Oxiracetam preparation process is simpler, but obtained Oxiracetam cannot distinguish between (S)-Aura west therein
Smooth and (R)-Oxiracetam.Limitation is brought for subsequent utilize.
It there is no the technique report that (S)-Oxiracetam or (R)-Oxiracetam are prepared using Oxiracetam acid as raw material at present.
Therefore one kind is developed using Oxiracetam acid as raw material, and the Oxiracetam isomers (S)-for preparing high quality in high yield is difficult to understand
The method of La Xitan and (R)-Oxiracetam, two kinds of isomers for industrially largely preparing Oxiracetam have important meaning
Justice.
Invention content
In view of this, one of the objects of the present invention is to provide a kind of method of separation Oxiracetam lactone salt isomers,
(1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt and (1R, 5S), (1S, 5S) type Oxiracetam acid lactone can be isolated
Salt, and reaction condition is mild, easy to operate, reaction efficiency is high, product yield high.
The second object of the present invention is to provide a kind of preparation method of Oxiracetam isomers, can prepare (S)-
Oxiracetam and (R)-Oxiracetam, reaction condition is mild, product yield high.
To achieve the above object, the technical scheme is that：
A method of separation Oxiracetam lactone salt isomers, by Oxiracetam lactone and D (+) -10- camphorsulfonic acids in
Reaction generates Oxiracetam acid lactone salt in non-protonic solvent, and reaction equation is as follows：
(1R, 5R), the crystallization of (1S, 5R) type Oxiracetam acid lactone salt are precipitated in reaction system, (1R, 5S), (1S, 5S) type
Oxiracetam acid lactone salt is stored in solution；
(1R, the 5R), (1S, 5R), (1R, 5S), (1S, 5S) type Oxiracetam acid lactone salt structural formula be respectively formula
I, Formula II, formula III, shown in formula IV：
As a preferred option, above-mentioned to react on insulated and stirred reaction 30min-3h at 40-60 DEG C.
As a preferred option, there is the process of low temperature growing the grain after reaction generation Oxiracetam acid lactone salt.
Further, the low temperature growing the grain is specially：It is cooled to -10~0 DEG C, growing the grain 1-3 hours.
Preferably, low temperature growing the grain keeps the temperature 2 hours for 0 DEG C.
As a preferred option, above-mentioned non-protonic solvent is selected from acetone, dimethyl sulfoxide (DMSO), acetonitrile, hexamethylene, dichloromethane
Alkane, chloroform it is one or more.
Further, preferably acetone.
As a preferred option, above-mentioned Oxiracetam lactone is generated by being dehydrated in Oxiracetam acid molecule.Reaction equation
For：
Further, preferably：Oxiracetam acid, a small amount of concentrated sulfuric acid are added in non-protonic solvent, temperature reaction, then
It is concentrated to dryness, obtains Oxiracetam acid lactone.
Preferably, above-mentioned non-protonic solvent is selected from acetone, dimethyl sulfoxide (DMSO), acetonitrile, hexamethylene, dichloromethane, trichlorine
Methane it is one or more.
Preferably, the above-mentioned concentrated sulfuric acid is 98% concentrated sulfuric acid, and addition is the 0.5%-2% of non-protonic solvent quality.
Preferably, 2% that 98% concentrated sulfuric acid amount is non-protonic solvent quality is added.
As a preferred option, above-mentioned temperature reaction temperature is 40-60 DEG C, and the time is 2-5 hours.
Further, temperature is 50 DEG C, and the time is 3 hours.
A method of separation Oxiracetam lactone salt isomers, specially：Filtering, collect in filter cake (1R, 5R), (1S,
5R) type Oxiracetam acid lactone salt collects (1R, 5S), (1S, 5S) type Oxiracetam acid lactone salt in filtrate.
As a preferred option, (1R, 5S) is collected, (1S, 5S) type Oxiracetam acid lactone salt is specially：Control temperature in
Filtrate decompression is dried to dry at 40-60 DEG C.
As a preferred option, (1R, 5R) is collected in filter cake, (1S, 5R) type Oxiracetam acid lactone salt is specially：Filter cake
It is washed with above-mentioned non-protonic solvent, collects filter cake, 40-60 DEG C of temperature of control is dried under reduced pressure.
The preparation method of Oxiracetam isomers, it may include following steps：
1) according to the method for purpose one obtain (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt and (1R, 5S), (1S,
5S) type Oxiracetam acid lactone salt；
2) (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt or (1R, 5S), (1S, 5S) type Austria that step 1) obtains
La Xitan acid lactone salt is dissolved in polar organic solvent, leads to ammonia, and reaction generates (R)-Oxiracetam, (S)-Oxiracetam.
The above-mentioned reaction equation for preparing Oxiracetam isomers is：
Wherein, Formula V is (R)-Oxiracetam, and Formula IV is (S)-Oxiracetam.
As a preferred option, the step 2) polar organic solvent is methanol, ethyl alcohol, normal propyl alcohol, isopropanol, the tert-butyl alcohol
It is one or more.
Further, preferably methanol.
As a preferred option, also comprising water in the step 2) reaction system, the volume of the water is anti-no more than described
Answer the 2% of system volume.
As a preferred option, include also low temperature growing the grain after reaction generates Oxiracetam, be filtered, washed, recrystallize, filtering
With dry process.
Further, above-mentioned low temperature growing the grain is specially to be cooled to -10~0 DEG C, growing the grain 1-3 hours.
Preferably, low temperature growing the grain keeps the temperature 2 hours for 0 DEG C.
Further, above-mentioned recrystallization process is specially：Water and a small amount of glacial acetic acid is added to be warming up to 40-70 DEG C of dissolving, after dissolved clarification
It filters while hot, then filtrate slow cooling is cooled to 0-10 DEG C of growing the grain to 40~45 DEG C of heat preservation crystallizations.
As a preferred option, step 2) can be optimized for：
A. after Oxiracetam acid lactone salt is dissolved in polar organic solvent, -10~10 DEG C are cooled to, leads to ammonia, adds a small amount of water,
The volume of the water is no more than the 2% of reaction system volume；Insulated and stirred is reacted 10-24 hours at 15~30 DEG C, and reaction generates
(S)-Oxiracetam, (R)-Oxiracetam；
B. it is cooled to -10~0 DEG C, growing the grain 1-3 hours filters to obtain filter cake, and polar organic solvent washs described in step a,
Obtain (S)-Oxiracetam and/or (R)-Oxiracetam crude product.
Further, above-mentioned steps a Oxiracetams acid lactone salt is stirred to react 15 hours with ammonia at 25 DEG C.
To sum up, it is preferable that the preparation method of Oxiracetam isomers of the invention may include following steps：
1) Oxiracetam acid generates Oxiracetam lactone in intramolecular dehydration, is concentrated under reduced pressure and obtains in dry Oxiracetam
Ester；
2) lactone that step 1) obtains, which is reacted with D (+) -10- camphorsulfonic acids in non-protonic solvent, generates Oxiracetam
Acid lactone salt, low temperature growing the grain filter, and (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt are collected in filter cake, is collected in filtrate
(1R, 5S), (1S, 5S) type Oxiracetam acid lactone salt；
3) (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt or (1R, 5S), (1S, 5S) type Austria that step 2) obtains
La Xitan acid lactone salt is dissolved in polar organic solvent, leads to ammonia, and reaction generates (R)-Oxiracetam, (S)-Oxiracetam.Instead
Answer equation as follows：
The beneficial effects of the present invention are：
1) the present invention provides the methods of separation Oxiracetam acid lactone salt isomers, and provide by above-mentioned isomers point
The method for not preparing (S)-Oxiracetam, (R)-Oxiracetam.
2) separation method of Oxiracetam isomers provided by the invention only obtains Oxiracetam lactone salt by filtering
Isomers, it is easy to operate, and can be used in preparing (S)-Oxiracetam and (R)-Oxiracetam, enormously simplify Oxiracetam
The preparation process of isomers.
3) reaction condition is mild, and product yield is up to 60%, is higher than the yield of the prior art, is suitable for industrialized large-scaled production.
Specific implementation mode
It detailed description of a preferred embodiment of the present invention will be given below.The reality of actual conditions is not specified in preferred embodiment
Proved recipe method, usually according to normal condition, illustrated embodiment are but not to be to preferably be illustrated to present disclosure
Present disclosure is only limitted to illustrated embodiment.So those skilled in the art according to foregoing invention content to embodiment party
Case carries out nonessential modifications and adaptations, still falls within protection scope of the present invention.
Embodiment 1 includes the preparation of the reaction system of Oxiracetam acid lactone salt isomers
1. preparing Oxiracetam lactone
100g Oxiracetams acid, the 2g concentrated sulfuric acids are added in 200g acetone, is warming up at 50 DEG C and is stirred to react 3 hours, so
After be concentrated to dryness, obtain Oxiracetam acid lactone, this step yield is based on 100%.
2. preparing the reaction system of (1R, 5R), (1S, 5R) and (1R, 5S), (1S, 5S) type Oxiracetam acid lactone salt
400g acetone and 144gD (+) -10- camphorsulfonic acids, heating are added in the Oxiracetam acid lactone obtained to step 1
Insulated and stirred reacts 1h to 50 DEG C, is then cooled at 0 DEG C and keeps the temperature growing the grain 2h.
At this point, (1R, 5R), the crystallization of (1S, 5R) type Oxiracetam acid lactone salt are precipitated in reaction system, (1R, 5S), (1S,
5S) type Oxiracetam acid lactone salt is stored in solution.Obtain the reactant for including Oxiracetam acid lactone salt isomers of the present invention
System.
The separation of isomers in reaction system of the embodiment 2 comprising Oxiracetam acid lactone salt isomers
1) reaction system of Example 1, filtering, filter cake are washed with 40g acetone, collect filter cake, and control temperature 50 C subtracts
It press dry dry 6 hours, obtains (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt；
3) filtrate is collected, control temperature is dried under reduced pressure at 50 DEG C to doing, and obtains (1R, 5S), (1S, 5S) type Oxiracetam acid
Lactone salt.
The preparation of embodiment 3 (R) type Oxiracetam
1) 160g methanol is added into embodiment 2 (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt, is cooled to 10
DEG C hereinafter, 2ml water is added, 24g ammonias are passed through, lead to ammonia and is warming up at 25 DEG C insulated and stirred and reacted 15h, controlled, lead in sampling
Peak purity about 97%, starting material left 2%；
2) reaction terminates to be cooled to 0 DEG C of heat preservation growing the grain 2h, filtering, and filter cake is washed with 20g methanol, obtains (R) type Oxiracetam
Crude product；
3) add 40g water and 0.1g glacial acetic acid to be warming up at 60 DEG C and dissolve, filtered while hot after dissolved clarification, filtrate slow cooling to 40
~45 DEG C of heat preservation crystallization 30min, are then cooled to 5 DEG C of growing the grain 2h, and filtering, the 20g methanol being pre-chilled wash filter cake, obtains 31.5g (R)
Type Oxiracetam wet product, 55 DEG C of temperature of control are dried under reduced pressure 6 hours；30.5g (R) type Oxiracetam is obtained, mass yield 61% is pure
Degree >=99.8%.
The preparation of embodiment 4 (S) type Oxiracetam
1) 160g methanol is added into embodiment 2 (1R, 5S), (1S, 5S) type Oxiracetam acid lactone salt, is cooled to 10
DEG C hereinafter, 2ml water is added, 24g ammonias are passed through, lead to ammonia and is warming up at 25 DEG C insulated and stirred and reacted 15h, controlled, lead in sampling
Peak purity about 97%, starting material left 2%；
2) reaction terminates to be cooled to 0 DEG C of heat preservation growing the grain 2h, filtering, and filter cake is washed with 20g methanol, obtains (S) type Oxiracetam
Crude product；
3) add 40g water and 0.1g glacial acetic acid to be warming up at 60 DEG C and dissolve, filtered while hot after dissolved clarification, filtrate slow cooling to 40
~45 DEG C of heat preservation crystallization 30min, are then cooled to 5 DEG C of growing the grain 2h, filter, and the 20g methanol washing filter cake of precooling is added, obtains 31g
(S) type Oxiracetam wet product, 55 DEG C of temperature of control are dried under reduced pressure 6 hours；30g (S) type Oxiracetam, mass yield 60%,
Purity >=99.8%.
The preparation method of Oxiracetam isomers provided by the invention can detach the isomers of Oxiracetam lactone salt, and
It is used to prepare (S)-Oxiracetam and (R)-Oxiracetam, does not waste material.And reaction condition is mild, product yield height, quality
Height is suitable for industrialized large-scaled production.
Finally illustrate, the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although with reference to compared with
Good embodiment describes the invention in detail, it will be understood by those of ordinary skill in the art that, it can be to the skill of the present invention
Art scheme is modified or replaced equivalently, and without departing from the objective and range of technical solution of the present invention, should all be covered at this
In the right of invention.
Claims (10)
1. a kind of method of separation Oxiracetam lactone salt isomers, which is characterized in that by Oxiracetam lactone and D (+) -10-
Camphorsulfonic acid reacts in non-protonic solvent generates Oxiracetam acid lactone salt, filtering, collect in filter cake (1R, 5R), (1S,
5R) type Oxiracetam acid lactone salt collects (1R, 5S), (1S, 5S) type Oxiracetam acid lactone salt, reaction equation in filtrate
It is as follows：
Wherein Formulas I, Formula II, formula III, formula IV are respectively (1R, 5R), (1S, 5R), (1R, 5S), (1S, 5S) type Oxiracetam acid
Lactone salt.
2. according to the method described in claim 1, it is characterized in that, described react on insulated and stirred reaction at 40-60 DEG C
30min-3h。
3. according to the method described in claim 1, it is characterized in that, reaction has low temperature growing the grain after generating Oxiracetam acid lactone salt
Process, specially：It is cooled to -10~0 DEG C, growing the grain 1-3 hours.
4. according to the method described in claim 1, it is characterized in that, the non-protonic solvent be selected from acetone, dimethyl sulfoxide (DMSO),
Acetonitrile, hexamethylene, dichloromethane, chloroform it is one or more.
5. according to the method described in claim 1, it is characterized in that, by Oxiracetam acid molecule occurs for the Oxiracetam lactone
Interior dehydration generates.
6. the preparation method of Oxiracetam isomers, which is characterized in that include the following steps：
1) detach according to the method for claim 1 (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt and (1R, 5S),
(1S, 5S) type Oxiracetam acid lactone salt；
2) (1R, 5R), (1S, 5R) type Oxiracetam acid lactone salt or (1R, 5S), (1S, 5S) the type Aura west that step 1) obtains
Smooth acid lactone salt is dissolved in polar organic solvent, leads to ammonia, and reaction generates (R)-Oxiracetam, (S)-Oxiracetam.
7. preparation method according to claim 6, which is characterized in that the step 2) polar organic solvent is methanol, second
Alcohol, normal propyl alcohol, isopropanol, the tert-butyl alcohol it is one or more.
8. preparation method according to claim 6, which is characterized in that also include water, institute in the step 2) reaction system
The volume for stating water is no more than the 2% of the reaction system volume；
The condition of the step 2) reaction is that insulated and stirred is reacted 10-24 hours at 15~30 DEG C.
9. according to the method described in claim 6, it is characterized in that, including also low temperature growing the grain after step 2), being filtered, washed, again
Crystallization and dry process.
10. according to the method described in claim 9, it is characterized in that, the recrystallization is specially：Add water and water quality in product
0.2%-0.5% glacial acetic acid, be warming up to 40-70 DEG C of dissolving, filtered while hot after dissolved clarification, filtrate slow cooling is to 40~45 DEG C
Crystallization is kept the temperature, 0-10 DEG C of growing the grain is then cooled to.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810764944.4A CN108659004B (en) | 2018-07-12 | 2018-07-12 | Preparation method of oxiracetam isomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810764944.4A CN108659004B (en) | 2018-07-12 | 2018-07-12 | Preparation method of oxiracetam isomer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108659004A true CN108659004A (en) | 2018-10-16 |
| CN108659004B CN108659004B (en) | 2020-11-10 |
Family
ID=63774024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810764944.4A Active CN108659004B (en) | 2018-07-12 | 2018-07-12 | Preparation method of oxiracetam isomer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108659004B (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0205247A2 (en) * | 1985-05-10 | 1986-12-17 | State Of Israel, Represented By Prime Minister's Office, Israel Institute For Biological Research | Derivatives of quinuclidine |
| KR20060010000A (en) * | 2004-07-27 | 2006-02-02 | 한국화학연구원 | Process for preparation of (s) or (r)-oxiracetam |
| CN102633686A (en) * | 2011-02-09 | 2012-08-15 | 重庆福安药业(集团)股份有限公司 | Preparation method of peramivir |
| CN104693108A (en) * | 2013-12-06 | 2015-06-10 | 重庆博腾制药科技股份有限公司 | Preparation method of Bruton's tyrosine kinase (Btk) intermediate |
| CN105899487A (en) * | 2013-12-27 | 2016-08-24 | 株式会社Api | Method for producing 5-hydroxypiperidine-2-carboxylic acid |
| CN106146379A (en) * | 2013-06-19 | 2016-11-23 | 成都百途医药科技有限公司 | A kind of synthetic method of oxiracetam |
| CN106349144A (en) * | 2016-08-30 | 2017-01-25 | 山东默得森生物制药有限公司 | Preparation method of (S)-oxiracetam intermediate |
| WO2018011823A1 (en) * | 2016-07-13 | 2018-01-18 | Mylan Laboratories Limited | Salt of amine-protected (1s,2r,4s)-1,2-amino-n,n-dimethylcyclohexane-4-carboxamide |
| CN107750245A (en) * | 2015-05-13 | 2018-03-02 | 詹森药业有限公司 | (S) the CSA salt of S ketamines, (R) the CSA salt of S ketamines and the method for preparing S ketamines |
-
2018
- 2018-07-12 CN CN201810764944.4A patent/CN108659004B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0205247A2 (en) * | 1985-05-10 | 1986-12-17 | State Of Israel, Represented By Prime Minister's Office, Israel Institute For Biological Research | Derivatives of quinuclidine |
| KR20060010000A (en) * | 2004-07-27 | 2006-02-02 | 한국화학연구원 | Process for preparation of (s) or (r)-oxiracetam |
| CN102633686A (en) * | 2011-02-09 | 2012-08-15 | 重庆福安药业(集团)股份有限公司 | Preparation method of peramivir |
| CN106146379A (en) * | 2013-06-19 | 2016-11-23 | 成都百途医药科技有限公司 | A kind of synthetic method of oxiracetam |
| CN104693108A (en) * | 2013-12-06 | 2015-06-10 | 重庆博腾制药科技股份有限公司 | Preparation method of Bruton's tyrosine kinase (Btk) intermediate |
| CN105899487A (en) * | 2013-12-27 | 2016-08-24 | 株式会社Api | Method for producing 5-hydroxypiperidine-2-carboxylic acid |
| CN107750245A (en) * | 2015-05-13 | 2018-03-02 | 詹森药业有限公司 | (S) the CSA salt of S ketamines, (R) the CSA salt of S ketamines and the method for preparing S ketamines |
| WO2018011823A1 (en) * | 2016-07-13 | 2018-01-18 | Mylan Laboratories Limited | Salt of amine-protected (1s,2r,4s)-1,2-amino-n,n-dimethylcyclohexane-4-carboxamide |
| CN106349144A (en) * | 2016-08-30 | 2017-01-25 | 山东默得森生物制药有限公司 | Preparation method of (S)-oxiracetam intermediate |
Non-Patent Citations (2)
| Title |
|---|
| 李坤等: "促智药物(S)-奥拉西坦的合成", 《中国新药杂志》 * |
| 杨帆等: "D-对羟基苯甘氨酸的不对称转化拆分", 《中国医药工业杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108659004B (en) | 2020-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2839344B2 (en) | Method for producing cyclic amino acid and intermediate thereof | |
| CN105814020B (en) | Method for mass producing 1 [(2 bromophenyl) sulfonyl] 5 methoxyl group 3 [(4 methyl, 1 piperazinyl) methyl] 1H indoles dimethanesulfonate monohydrates | |
| CN110590746A (en) | Preparation method of low-impurity vonoprazan fumarate | |
| RU2387656C2 (en) | Method for synthesis of galantamine hydrobromide | |
| CN112062712A (en) | Preparation method of 2- (5-bromo-3-methylpyridin-2-yl) acetic acid hydrochloride | |
| WO2012134392A1 (en) | Process for the production of a pemetrexed salt | |
| CN108659004A (en) | The preparation method of Oxiracetam isomers | |
| CN108314696B (en) | Utilization method of 2-hydroxy-1, 3, 5-tri-O-benzoyl-alpha-D-ribofuranose crystallization mother liquor | |
| CN106588888B (en) | Method for preparing high-purity L-sunitinib malate | |
| CN113072514B (en) | Preparation method of Xuanjinning and intermediate thereof | |
| AU2009264395B2 (en) | Process for the preparation of clopidogrel hydrogen sulfate crystalline form I | |
| CN111196771B (en) | Compound, preparation method thereof and application thereof in preparation of brivaracetam | |
| EA022300B1 (en) | Separation of 2-amino-3,6-dihydro-4-dimethylamino-6-methyl-1,3,5-triazine enantiomers using tartaric acid | |
| EP1564209A1 (en) | Process for the preparation of 13-cis-retinoic acid | |
| CN106187864A (en) | A kind of method being prepared high-purity bupivacaine alkali by bupivacaine hydrochloride | |
| SU831078A3 (en) | Lidene/thioxanthen-2-sulfamide | |
| CN113004245B (en) | Preparation method of desloratadine | |
| KR100704641B1 (en) | Methods for the preparation of levofloxacin having a high purity | |
| CN103012264A (en) | Method for resolving 3-substituted amino-hexahydro-1H-azacycloheptane | |
| CN112225736B (en) | Preparation method of 6-bromoimidazo [1.2-a ] pyridine-3-formaldehyde | |
| SU540867A1 (en) | Method for preparing cis-dimethyl9- / 3- (4-methyl-1-piperazinyl) -propylidene / -thioxanthene-2-sulfonamide | |
| EP4083045B1 (en) | Novel method for synthesizing decursin derivative | |
| CN109988092B (en) | Preparation method of nefiracetam for treating Alzheimer disease | |
| JPH03279348A (en) | Production of 2,4,5-trifluoro-3-alkoxybenzoic acid | |
| CN109096107B (en) | Preparation method of 5-formyl-2-methoxy methyl benzoate |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |