CN110066220A - A kind of preparation method of selegiline - Google Patents
A kind of preparation method of selegiline Download PDFInfo
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- CN110066220A CN110066220A CN201910458791.5A CN201910458791A CN110066220A CN 110066220 A CN110066220 A CN 110066220A CN 201910458791 A CN201910458791 A CN 201910458791A CN 110066220 A CN110066220 A CN 110066220A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/60—Preparation of compounds containing amino groups bound to a carbon skeleton by condensation or addition reactions, e.g. Mannich reaction, addition of ammonia or amines to alkenes or to alkynes or addition of compounds containing an active hydrogen atom to Schiff's bases, quinone imines, or aziranes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/62—Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Abstract
The present invention provides a kind of preparation methods of selegiline, comprising: after compound (i) is carried out acyl chloride reaction, carries out acylation reaction with benzene, after carbonyl reduction and deacylation base, carries out propargylation, obtain selegiline；In compound (i), R is methyl, ethyl, trifluoromethyl, phenyl or benzyl.In the present invention, using acyl group-D-N- methylalanine class compound as raw material, by being acylated; carbonyl reduction and the reaction of deacylation base and propargylation obtain selegiline, and not only raw material simplicity is easy to get, but also reaction step is few; it is easy to operate, without using risk or high price reagent raw material.Meanwhile in the present invention, without carrying out chiral resolution to intermediate or final product, product ee value is high, yield is high, is suitable for scale, industrialized production.
Description
Technical field
The present invention relates to pharmaceutical synthesis fields, in particular to a kind of preparation method of selegiline.
Background technique
Selegiline (Selegilin) is a kind of selective monoamine oxidase B (MAO-B) irreversible inhibition agent, can
The metabolism for blocking dopamine, inhibits the degradation of dopamine, also can inhibit the reuptake of synaptic dopamine and extends dopamine effect
Time.It is shared with levodopa, the effect of levodopa can be enhanced, and can reduce dyskinesia caused by levodopa.Department
Carry out lucky orchid to list in 1993, is currently used primarily in the treatment of Parkinson's disease, alzheimer's disease and depression.
The synthesis of selegiline has many pertinent literature reports, for example, Zhang Lijuan of Shenyang Pharmaceutical University et al. exists
It reports within 2005 and a kind of the side of selegiline hydrochloride is obtained with 42% yield by four steps using amphetamine as raw material
Method, specific reaction route are as follows:
However, raw materials used amphetamine is the chemicals of country's control in this method, it is not easy to granted card, separately
After outer use is split, the product quantity of at least half is wasted, therefore cost is also higher, and general company is also not easy to obtain
Criticize the chemicals using such control.
Talluri et al. reported a kind of method for synthesizing selegiline by 9 steps as raw material using benzenpropanal in 2007,
Specific reaction route is as follows:
However, dangerous nitrine reagent, combustible metal reagent Lithium Aluminium Hydride, sodium hydride, hydroboration can be used in this method
Sodium, the reagents such as mesyl chloride of stench, this also causes this method industrialization cost not have advantage, and amplification risk is excessively high.
2010, Bomholdt et al. was with D- Propanolamine through special protective preparation, and into peroxidating, grignard reaction etc. synthesizes end
Product, specific reaction route are as follows:
In this method, with combustible metal reagent sodium cyanoborohydride, Grignard Reagent, the thioacetic acid of stench, dimethyl sulphide
For raw material, and ultralow temperature is needed to react, while also needed using expensive protective agent, industrializing cost does not have advantage, amplification danger
It is dangerous excessively high.
2011, Kondekar was using phenylacetaldehyde as raw material, by 9 step asymmetric syntheses end product, reaction route with specific reference to
It is as follows:
And in this method, it also needs with nitrine reagent, combustible metal reagent Lithium Aluminium Hydride, sodium hydride, sodium borohydride, cyanogen
Base sodium borohydride, pivaloyl chloride, mesyl chloride, the dimethyl sulphide of stench are raw material, and need low-temp reaction.Meanwhile it is chiral
Catalyst is difficult to obtain, and industrialization cost does not have advantage, and amplification risk is excessively high.
2015, Lalwani et al. reacts to obtain ee value by raw material of trans- -3- phenyl -2- alkene-propyl alcohol by eight steps was
98% product, specific reaction route are as follows:
In this method, dangerous nitrine reagent can be equally used, combustible metal reagent Lithium Aluminium Hydride, sodium hydride, stench
Mesyl chloride, low-temp reaction；Likewise, the method is also required to using the chiral catalyst being difficult to obtain, industrializing cost does not have
Advantage, amplification risk are excessively high.
2016, Dey et al. obtained the product department that ee value is 98% according to following reaction route, with 30.18% yield
Carry out lucky orchid, specific reaction route is as follows:
However, this method reaction needs 8 steps, reaction route is too long, and needs using dangerous nitrine reagent, inflammable gold
Belong to reagent Lithium Aluminium Hydride, pregnancy base silane potassium, sodium borohydride, the pivaloyl chloride of stench, paratoluensulfonyl chloride, low-temp reaction.Work
Industry, which is melted into this, does not have advantage, and amplification risk is excessively high.
2018, Yecheng was uncommon et al. with first azanol, and acetaldehyde and benzaldehyde etc. are raw material, using special chiral catalyst glimmering
Light light irradiation synthesizes the selegiline end product that ee value is 94%, and reaction route is as follows:
However, catalyst is not easily-synthesized in this method, it is also necessary to be reacted using illumination condition, industrialization is not easy reality
It is existing, expensive equipment must be bought realizing.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first object of the present invention is to provide a kind of preparation method of selegiline, and the preparation method has raw material
The advantages that simplicity is easy to get, and reaction step is simple, and product purity is high, and yield is high.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
A kind of preparation method of selegiline, comprising: after compound (i) is carried out acyl chloride reaction, carry out acyl group with benzene
Change reaction, after carbonyl reduction and deacylation base, carries out propargylation, obtain selegiline；Wherein, compound (i) structure
It is as follows:In compound (i), R is methyl, ethyl, trifluoromethyl, phenyl or benzyl.
Compared with prior art, the invention has the benefit that
In the present invention, using acyl group-D-N- methylalanine class compound as raw material, by being acylated, carbonyl reduction and de-
Acyl group reaction and propargylation obtain selegiline, and not only raw material simplicity is easy to get, but also reaction step is few, easy to operate,
Without using risk or high price reagent raw material.Meanwhile in the present invention, without carrying out chiral resolution to intermediate or final product,
Product ee value is high, yield is high, is suitable for scale, industrialized production.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
It is difficult to obtain in view of raw material present in existing selegiline preparation method, reaction route is long, reaction condition is severe
The problems such as quarter and low yield, the present invention provides a kind of new methods of selegiline synthesis, to solve institute in the prior art
The existing above problem.
The synthesis of selegiline of the present invention can refer to following steps progress:
(a) acyl group-D-N- methylalanine acyl chloride reaction.
It is to be with structure in this stepAcyl group-D-N- methylalanine be raw material, carry out acyl chlorides
Change reaction, obtain corresponding midbody compound:Reaction equation can refer to as follows:
In certain embodiments of the present invention, this step reaction carries out under solution condition, i.e., raw material (i) is added molten
In agent, chloride reagent is added, carries out acyl chloride reaction.
In currently preferred some embodiments, in compound (i), R is methyl, ethyl, trifluoromethyl, phenyl,
Or benzyl；
It is furthermore preferred that compound (i) are as follows: acetyl-D-N- methylalanine, trifluoroacetyl group-D-N- methylalanine, or
Person's benzoyl-D-N- methylalanine.
In currently preferred some embodiments, the solvent includes: methylene chloride, tetrahydrofuran, benzene, Huo Zheshu
At least one of butyl methyl ether.
In currently preferred some embodiments, the chloride reagent includes: thionyl chloride, oxalyl chloride, trichlorine
Change at least one of phosphorus or phosphorus pentachloride.
(b) step (a) product acid chlorideFriedel-crafts acylation is carried out with benzene, is obtainedReaction equation can refer to as follows:
This step is carried out under lewis acid catalysed conditions, it is preferred that lewis acid used includes: trichlorine in this step
Change aluminium, tin tetrachloride, boron chloride, sulfuric acid, ferric trichloride, at least one of boron trifluoride ether or zinc chloride.
(c) step (b) productThrough carbonyl reduction and deacylation base, obtain
Reaction equation can refer to as follows:
In certain embodiments of the present invention, in this step, carbonyl reduction reaction can be first carried out, is obtainedDeacylation base reaction is carried out again, is obtained
Alternatively, can also first carry out deacylation base reaction in this step, obtainIt is taken off again
Acyl group reaction, obtains
In currently preferred some embodiments, the carbonyl reduction reaction includes: by compound (iii)/chemical combination
Object (v ') carries out carbonyl reduction by metal/carried metal catalytic hydrogenation reaction；Or by compound (iii)/compound (v ')
With hydrazine hydrate, the reaction of the reducing agents such as zinc amalgam or triethylsilane carries out carbonyl reduction；
Preferably, metal/the metal supported catalyst includes: palladium carbon, Raney's nickel, in rhodium carbon and platinum carbon extremely
Few one kind.
In currently preferred some embodiments, the deacylation base includes: by compound (iii)/compound (iv)
Under basic or acidic conditions, carbonyl removing is carried out；
Preferably, the alkali such as sodium hydroxide solution or potassium hydroxide solution can be added in compound (iii)/compound (v)
Property reagent in, carry out carbonyl elimination reaction；
Preferably, compound (iii)/compound (v) can also be added in the acid reagents such as hydrochloric acid or sulfuric acid, is carried out
Carbonyl elimination reaction.
(d) step (c) productAfter propargylation, product selegiline is obtained, is reacted
Formula can refer to as follows:
It in certain embodiments of the present invention, is under alkaline reagent existence condition, by compound (v) in this step
It is reacted with propargylation reagent, obtains product selegiline.
In currently preferred some embodiments, in this step, alkaline reagent used includes: sodium carbonate, potassium carbonate,
In cesium carbonate, triethylamine, diisopropylamine, diisopropylethylamine or DBU (1,8- diazabicylo, 11 carbon -7- alkene) extremely
Few one kind.
In currently preferred some embodiments, in this step, propargyl reagent used includes: propargyl chloride, alkynes
At least one of propyl bromide or propargyl iodide (i.e. X=Cl, Br or I in above formula).
In reaction as above provided by the present invention, raw materials used equal simplicity is easy to get, and tries without using the metal of high activity
Agent is as raw material, and this is but also reaction process of the present invention is safer controllable, simultaneously as without carrying out chiral resolution
Product is obtained, thus also avoids splitting brought loss of product problem.
Embodiment 1
It weighs 145.16 (1mol) grams of acetyl-D-N- methylalanine to be dissolved in 1000ml methylene chloride, installation magnetic is added
In the 2000ml there-necked flask of power stirring, constant pressure funnel and return pipe, 130.86 grams of (1.1mol) thionyl chlorides are added dropwise, are added dropwise
After, it is heated to reflux 4 hours, it is spare dissolved with the dichloromethane solution of intermediate 2.
It weighs 399.99 grams of (3mol) alchlors to be dissolved in the methylene chloride of 1000ml, and adds with 156 grams of (2mol) benzene
Enter to install in the 3000ml there-necked flask of mechanical stirring, constant pressure funnel and condenser pipe, after stirring 1 hour, intermediate 2 is added dropwise
Dichloromethane solution is heated to reflux, and TLC monitoring has the generation of intermediate 3, remaining raw material disappears.Be down to 0 DEG C hereinafter, be added dropwise lye,
Temperature is kept not surpass 20 DEG C, pH is adjusted to 12 or so, extracts liquid separation, retains dichloromethane layer, and saturated common salt washing obtains in crude product
Mesosome 3 obtains sterling (150 grams, 73.2%) with recrystallizing methanol.
150 grams of intermediates 3 are weighed, are dissolved in 1000ml methanol, 2000ml is added and adds in hydrogen kettle, and 15 gram of 10% palladium is added
Charcoal is replaced with hydrogen after nitrogen displacement, is heated to 60 DEG C, is filled with 8 kilograms of pressure hydrogens (pressure decline just adds to 8 kilograms),
Do not change within 3 hours if pressure is kept for 8 kilograms, for end of reaction, cooling, palladium charcoal is recovered by filtration for pressure release, and filtrate addition etc. is worked as
The NaOH solution of the 3mol/L of amount is heated to 50 DEG C, stirring, after completion of the reaction, with the extraction of 500ml*2 methylene chloride, is concentrated to give
Mesosome 4 (107 grams, 98%)
107 grams of intermediates 4 and 139 grams of Anhydrous potassium carbonates are weighed, and are dissolved in 600ml acetonitrile solution, peace is then added
In the 1000ml there-necked flask for filling mechanical stirring, constant pressure funnel and condenser pipe, propargyl bromide solution is slowly added dropwise (by 85.6 grams
(0.72mol) propargyl bromide, which is dissolved in 100ml acetonitrile, to be obtained), it is added dropwise and is warming up to 50 DEG C, TLC, which is monitored to intermediate 4, to disappear
It loses.Solid is filtered, then acetonitrile is concentrated and is removed, water 500ml and ethyl acetate 500ml is added into residue, extracts liquid separation,
Water layer with 250ml*2 ethyl acetate, is extracted twice again, merges organic phase, and saturated common salt washing is dry, is concentrated to give 125 grams of whole product
(66.8%).
Reaction route is as follows:
Embodiment 2
It weighs 199.13 grams of (1mol) trifluoroacetyl group-D-N- methylalanines to be dissolved in 1000ml methylene chloride, be added
In the 2000ml there-necked flask for installing magnetic agitation, constant pressure funnel and return pipe, dropwise addition dropwise addition phosphorus pentachloride solution (by
45.76g (0.22mol) phosphorus pentachloride is dissolved in 100ml methylene chloride and obtains), after being added dropwise, 4 hours are heated to reflux, intermediate
2 dichloromethane solutions are spare.
It weighs 351.57 grams of (3mol) boron chlorides to be dissolved in the methylene chloride of 1000ml, and adds with 156 grams of (2mol) benzene
Enter to install in the 3000ml there-necked flask of mechanical stirring, constant pressure funnel and condenser pipe, after stirring 1 hour, intermediate 2 two is added dropwise
Chloromethanes stock solution, is heated to reflux, and TLC monitoring has the generation of intermediate 3, remaining raw material disappears.0 DEG C is down to hereinafter, alkali is added dropwise
Liquid keeps temperature not surpass 20 DEG C, and pH is adjusted to 12 or so, extracts liquid separation, retains dichloromethane layer, and saturated common salt washing obtains thick
Product intermediate 3 obtains sterling (185.97,71.74%) with recrystallizing methanol.
In 2000ml plus hydrogen kettle, 185 grams of intermediate 3 and 120 gram hydration hydrazine reactions are weighed；Then, equivalent is added
The NaOH solution of 3mol/L is heated to 50 DEG C, and stirring is extracted with 500ml*2 methylene chloride after completion of the reaction, is concentrated to give intermediate
4,101.18 grams, yield 95%.
101.18 grams of intermediates 4 and 130 grams of Anhydrous potassium carbonates are weighed, and are dissolved in 600ml acetonitrile solution, are then added
In the 1000ml there-necked flask for installing mechanical stirring, constant pressure funnel and condenser pipe, propargyl bromide solution is slowly added dropwise (by 95.2
Gram (0.80mol) propargyl bromide, which is dissolved in 100ml acetonitrile, to be obtained), it is added dropwise and is warming up to 50 DEG C, TLC, which is monitored to intermediate 4, to disappear
It loses.Solid is filtered, then acetonitrile is concentrated and is removed, water 500ml and ethyl acetate 500ml is added into residue, extracts liquid separation,
Water layer is extracted twice with the ethyl acetate of 250ml*2 again, merges organic phase, and saturated common salt washing is dry, is concentrated to give whole product 82.5
Gram, yield 65%.
2 reaction equation of embodiment is as follows:
Embodiment 3
It weighs 207.23 grams of (1mol) benzoyl-D-N- methylalanines to be dissolved in 1000ml methylene chloride, installation is added
In the 2000ml there-necked flask of magnetic agitation, constant pressure funnel and return pipe, 76.16 grams of (0.6mol) oxalyl chlorides are added dropwise, are added dropwise
After, it is heated to reflux 4 hours, 2 dichloromethane solution of intermediate is spare.
It weighs 399.99 grams of (3mol) alchlors to be dissolved in the methylene chloride of 1000ml, and adds with 156 grams of (2mol) benzene
Enter to install in the 3000ml there-necked flask of mechanical stirring, constant pressure funnel and condenser pipe, after stirring 1 hour, intermediate 2 two is added dropwise
Chloromethanes stock solution, is heated to reflux, and TLC monitoring has the generation of intermediate 3, remaining raw material disappears.0 DEG C is down to hereinafter, alkali is added dropwise
Liquid keeps temperature not surpass 20 degree, and pH is adjusted to 12 or so, extracts liquid separation, retains dichloromethane layer, and saturated common salt washing obtains thick
Product intermediate 3 obtains sterling 223g yield 72.3% with recrystallizing methanol.
200 grams of intermediates 3 are weighed, after the dissolution of 600ml methylene chloride, 432 grams of zinc amalgam reactions are added；Then, equivalent
In the KOH solution of 3mol/L, 50 DEG C, after being stirred to react are heated to, with the extraction of 1000ml*2 methylene chloride, organic phase concentration
Obtain 4 86.69 grams of yields 96.7% of intermediate.
Weigh 80 grams of intermediates 4 and 103.73 grams of Anhydrous potassium carbonates, be added installation mechanical stirring, constant pressure funnel and
In the 1000ml there-necked flask of condenser pipe, the solution that 66.64 grams of (0.7mol) propargyl bromides are dissolved in 80ml acetonitrile is slowly added dropwise, is added dropwise
It finishes and is warming up to 50 DEG C, TLC, which is monitored to intermediate 4, to disappear.Solid is filtered, then acetonitrile is concentrated and is removed, water is added in residue
500ml and ethyl acetate 500ml extracts liquid separation, and water layer is extracted twice with the ethyl acetate of 250ml*2 again, merges organic phase,
Saturated common salt washing, it is dry, it is concentrated to get 68.15 grams of yields 65.7% of target product.
3 reaction process of embodiment is shown below:
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from of the invention
Many other change and modification can be made in the case where spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (10)
1. a kind of preparation method of selegiline characterized by comprising
After compound (i) is carried out acyl chloride reaction, acylation reaction is carried out with benzene, after carbonyl reduction and deacylation base, is carried out
Propargylation obtains selegiline；
Wherein, compound (i) structure is as follows:
In compound (i), R is methyl, ethyl, trifluoromethyl, phenyl or benzyl.
2. preparation method according to claim 1, which is characterized in that the compound (i) are as follows: acetyl-D-N- methyl-prop
Propylhomoserin, trifluoroacetyl group-D-N- methylalanine or benzoyl-D-N- methylalanine.
3. preparation method according to claim 1, which is characterized in that the acyl chloride reaction includes:
Compound (i) is reacted under solvent existence condition with chloride reagent.
4. preparation method according to claim 3, which is characterized in that the chloride reagent includes: thionyl chloride, oxalyl
Chlorine, at least one of phosphorus trichloride or phosphorus pentachloride.
5. preparation method according to claim 3, which is characterized in that the solvent includes: methylene chloride, tetrahydrofuran,
At least one of benzene or t-butyl methyl ether.
6. preparation method according to claim 1, which is characterized in that the acylation reaction is in Louis acid catalysis condition
Lower progress；
Preferably, the lewis acid includes: alchlor, tin tetrachloride, boron chloride, sulfuric acid, ferric trichloride, boron trifluoride
At least one of ether or zinc chloride.
7. preparation method according to claim 1, which is characterized in that the carbonyl reduction includes: that metal/carried metal is urged
Change hydrogenation reaction carbonyl reduction, is hydrated hydrazine reaction carbonyl reduction, zinc amalgam reacts carbonyl reduction and triethylsilane reacts carbonyl
At least one of base reduction；
Preferably, the metal/carried metal catalytic hydrogenation reaction carbonyl reduction used catalyst includes: palladium carbon, Raney's nickel, rhodium
At least one of carbon and platinum carbon.
8. preparation method according to claim 1, which is characterized in that the deacylation base reaction is under acid or alkaline conditions
It carries out；
Preferably, the deacylation base reaction includes: to remove acyl group in sodium hydroxide or potassium hydroxide solution；
Preferably, the deacylation base reaction includes: to remove acyl group in hydrochloric acid or sulfuric acid.
9. preparation method according to claim 1, which is characterized in that the propargylation includes:
Under alkaline reagent existence condition, propargylation is carried out with propargyl reagent；
Preferably, the propargyl reagent includes: propargyl chloride, propargyl bromide, p-methyl benzenesulfonic acid allyl ester, methylsulphur allyl propionate
Or at least one of propargyl iodide.
10. preparation method according to claim 9, which is characterized in that the alkaline reagent includes: sodium carbonate, potassium carbonate,
Cesium carbonate, triethylamine, diisopropylamine, at least one of diisopropylethylamine or DBU.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067794A1 (en) * | 2004-12-22 | 2006-06-29 | Emmellen Biotech Pharmaceuticals Limited | A PROCESS FOR THE PREPARATION OF R-(-)-N, α-DIMETHYLPHENETHYLAMINE (LEVMETAMFETAMINE) OR S-(+)-N, α-DIMETHYLPHENETHYLAMINE (METHAMPHETAMINE) FROM d-EPHEDRINE OR L-EPHEDRINE RESPECTIVELY |
| CN102203053A (en) * | 2008-06-02 | 2011-09-28 | 基因里克斯(英国)有限公司 | An improved process for the preparation of amines |
| WO2013167988A1 (en) * | 2012-05-08 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of cough |
| WO2014174421A2 (en) * | 2013-04-22 | 2014-10-30 | Mahesh Kandula | Compositions and methods for the treatment of respiratory diseases |
-
2019
- 2019-05-29 CN CN201910458791.5A patent/CN110066220A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067794A1 (en) * | 2004-12-22 | 2006-06-29 | Emmellen Biotech Pharmaceuticals Limited | A PROCESS FOR THE PREPARATION OF R-(-)-N, α-DIMETHYLPHENETHYLAMINE (LEVMETAMFETAMINE) OR S-(+)-N, α-DIMETHYLPHENETHYLAMINE (METHAMPHETAMINE) FROM d-EPHEDRINE OR L-EPHEDRINE RESPECTIVELY |
| CN102203053A (en) * | 2008-06-02 | 2011-09-28 | 基因里克斯(英国)有限公司 | An improved process for the preparation of amines |
| WO2013167988A1 (en) * | 2012-05-08 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of cough |
| WO2014174421A2 (en) * | 2013-04-22 | 2014-10-30 | Mahesh Kandula | Compositions and methods for the treatment of respiratory diseases |
Non-Patent Citations (6)
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Application publication date: 20190730 |