CN105732467A - Preparation method of panobinostat - Google Patents
Preparation method of panobinostat Download PDFInfo
- Publication number
- CN105732467A CN105732467A CN201610019918.XA CN201610019918A CN105732467A CN 105732467 A CN105732467 A CN 105732467A CN 201610019918 A CN201610019918 A CN 201610019918A CN 105732467 A CN105732467 A CN 105732467A
- Authority
- CN
- China
- Prior art keywords
- dmf
- methanol
- solvent
- methyl
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Abstract
The invention discloses a preparation method of panobinostat. The preparation method comprises the following steps: adding phenylhydrazine and an absolute methanol 4A molecular sieve into a three-necked flask, adding 5-chloro-2-pentanone, and then adding methanol; filtering a reaction solution, decompressing the filtrate, and removing methanol in an evaporation manner; washing, filtering, and decompressing and concentrating the filtrate to obtain a brownish red viscose material 2-methyltryptamine; step II: adding 4-methyl cinnamate, DMF, glacial acetic acid and NBS into the three-necked flask, heating to 10 to 170 DEG C under the protection of nitrogen, and reacting for 1 to 7 h; and generating a faint yellow oily material. DMF+CH3COOH is adopted in the process, so that the toxicity is reduced on the selection of the solvent; and the subsequent reaction is also carried out under the DMF solvent, so that the solvent treatment is reduced, and the purity of an intermediate is improved. The preparation method is economical, environment-friendly, low in toxicity and very high in market application value.
Description
Technical field
The present invention relates to a kind of pharmaceutical methods, in particular, the preparation of a kind of panobinostat (LBH589)
Method.
Background technology
PTS Farydak(panobinostat that Novartis on February 25, (Novartis) developed in 2015, LBH589)
The final FDA of acquisition favors.Farydak(panobinostat) it is a kind of novel, wide spectrum histone deacetylase (HDAC) suppression
Agent, has a kind of new mechanism of action, plays a role by blocking histone deacetylase (HDAC), and this medicine can be to cancerous cell
Impose serious stress be until it be dead, healthy cell is the most unaffected.
Pharmaceutical college of East China University of Science has delivered " synthesis of LBH589 ", and this technical scheme exists certain shortcoming:
1. the solvent that the first step is selected is not reaching to the requirement of economy, also has and can substitute than better suited solvent.
2. first step initial reaction temperature is slightly higher, higher with production process equipment requirements in operation, thus improves cost.
3. CCl on second step solvent4Liver poison is more severe, and in laboratory or production process, suction can cause health not
Suitable, liver, kidney there are is serious infringement.Spilling causes pipeline long term accumulation and damaged.
4. second step post processing is cumbersome, and NBS is insoluble in CCl4,Needs are dividedly in some parts, complex operation.
5.BPO easily produces O2, it being unfavorable for that reaction is carried out, reaction needs N2Carry out under protection.
6.CCl4With the post processing of BPO, this technology directly revolves steaming CCl4, it is easier to suck.It is the most in production process BPO,
It is not processed by the program, causes impurity many.
Prior art existing defects needs to improve.
Summary of the invention
The technical problem to be solved is to provide one to be had raw material and is easy to get, economic and environment-friendly low toxicity, and post processing is held
The preparation method of easy a kind of panobinostat (LBH589).
Technical scheme is as follows: the preparation method of a kind of panobinostat (LBH589), including following step
Rapid:
Step one: phenylhydrazine, absolute methanol 4A molecular sieve are added in three-neck flask, adds first after adding the chloro-2 pentanone of 5-
Alcohol;By reacting liquid filtering, filtrate decompression is evaporated off methanol;Again by washing, filtrate reduced in volume after filtration, obtain brownish red thickness
Thing 2-methyltryptamine;
Step 2: join in three-necked bottle by 4-methyl cinnamic acid methyl ester, DMF, glacial acetic acid and NBS, is warming up under nitrogen protection
10 DEG C-170 DEG C reaction 1-7h;Generate pale yellow oil;This process uses DMF+CH3COOH, solvent selects to reduce poison
Property, subsequent reactions also needs to react under DMF solvent, therefore decreases the purity that solvent processes and improves intermediate;
Step 3: 2-methyltryptamine and DMF are added in three-necked bottle, adds and stir from N mono-diisopropylethylamine, add (E)-4-
Bromomethyl methyl cinnamate, dry DMF are reacted;Filter dried for reactant liquor washing;Obtain khaki solid (E)-3-[4-[[2-
(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. hydrochlorate;
Step 4: by (E)-3-[4-[[2-(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. salt
Hydrochlorate and absolute methanol add cooling in three-necked bottle, and dropping contains methanol solution and the reaction of light amine methanol solution of potassium hydroxide;Add
Potassium hydroxide solution stirs;Instill elutriation and go out a small amount of unreacted raw material completely;Filter, drip salt acid for adjusting pH 7-8, have solid
Body separates out;Filtering, filter cake washs through cold methanol, obtains, with recrystallization, the faint yellow solid LBH589 raw material that purity is higher after drying
Medicine.
Using such scheme, the present invention adopts technical solution of the present invention what advantage or beneficial effect, described advantage or useful
Effect is brought by technical solution of the present invention.
1. first this technical scheme reduces cost on solvent selects, absolute methanol: dehydrated alcohol=20000/ ton:
4000/ ton.
2. decrease to some degree in reaction temperature simultaneously, methanol boiling point 67 DEG C: ethyl alcohol boiling point 78 DEG C, relatively industry
Produce or small operation, equipment requirements is reduced, more preferably operate and cost-effective.
3.(E)-4-bromomethyl methyl cinnamate building-up process have employed DMF+CH3COOH
1). carbon tetrachloride liver poison is more severe, and in laboratory or production process, suction can cause uncomfortable, has liver, kidney
Serious infringement.Spilling causes pipeline long term accumulation and damaged.The change of solvent largely reduces toxicity, and is easier place
Reason solvent.
2). subsequent reactions also needs to react under DMF solvent, therefore decreases solvent and processes and improve the pure of intermediate
Degree.
3). original scheme does not has purity, and our scheme is in the case of productivity is constant, the also purity of more than 98%.
This preparation method is more economically saved the most in general, is environment-friendly and low-toxicity, convenient post-treatment, and having the highest market should
By value.
Accompanying drawing explanation
Fig. 1 is that the LC-MS of the present invention detects analysis chart;
Fig. 2 is that the HPLC of the present invention detects analysis chart;
Fig. 3 is that the NMR of the present invention detects analysis chart.
Detailed description of the invention
For the ease of understanding the present invention, below in conjunction with the accompanying drawings and specific embodiment, the present invention will be described in more detail.
This specification and accompanying drawing thereof give the preferred embodiment of the present invention, but, the present invention can be in many different forms
Realize, however it is not limited to the embodiment described by this specification.On the contrary, providing the purpose of these embodiments is to make the present invention
The understanding of disclosure more thorough comprehensively.
As shown in Figure 1, Figure 2, Figure 3 shows, one embodiment of the present of invention is, preferred plan,
The preparation method of a kind of panobinostat (LBH589), comprises the following steps:
Step one: phenylhydrazine, absolute methanol 4A molecular sieve are added in three-neck flask, adds first after adding the chloro-2 pentanone of 5-
Alcohol.By reacting liquid filtering, filtrate decompression is evaporated off methanol;Again by washing, filtrate reduced in volume after filtration, obtain brownish red thickness
Thing 2-methyltryptamine;This process solvent uses the methanol that price is lower instead, is to a certain degree reducing reaction temperature simultaneously.Work relatively
Industry produces or small operation, all more preferably operates and cost-effective;
Step 2: join in three-necked bottle by 4-methyl cinnamic acid methyl ester, DMF, glacial acetic acid and NBS, is warming up under nitrogen protection
70 DEG C of reaction 4h;Generate pale yellow oil;This process uses DMF+CH3COOH, solvent selects to reduce toxicity, and after locate
Reason is easier;Subsequent reactions also needs to react under DMF solvent, therefore decreases solvent and processes and improve the pure of intermediate
Degree;
Step 3: 2-methyltryptamine and DMF are added in three-necked bottle, adds and stir from N mono-diisopropylethylamine, add (E)-4-
Bromomethyl methyl cinnamate, dry DMF are reacted;Filter dried for reactant liquor washing;Obtain khaki solid (E)-3-[4-[[2-
(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. hydrochlorate;
Step 4: by (E)-3-[4-[[2-(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. salt
Hydrochlorate and absolute methanol add cooling in three-necked bottle, and dropping contains methanol solution and the reaction of light amine methanol solution of potassium hydroxide;Add
Potassium hydroxide solution stirs;Instill elutriation and go out a small amount of unreacted raw material completely;Filter, drip salt acid for adjusting pH 7-8, have solid
Body separates out;Filtering, filter cake washs through cold methanol, obtains, with recrystallization, the faint yellow solid LBH589 raw material that purity is higher after drying
Medicine.
The preparation (S-2) of embodiment 1 2-methyltryptamine
19.8 mL phenylhydrazines, 80 mL absolute methanols and 3 g 4A molecular sieves are sequentially added in 500mL three-neck flask, slow under room temperature
The slow dropping 25 chloro-2 pentanones of mL 5-.Drip to finish and add 120 mL methanol, slow temperature rising reflux 4h.Reactant liquor is cooled to room temperature,
Filtering, filtrate decompression is evaporated off methanol.Add 200 mL water, with 150 mL ethyl acetate wash 3 times, add 100 mL toluene and
Saturated 40 mL sodium bicarbonate solutions.Stirring, discards toluene phase.Aqueous phase adds 300 mL toluene, is stirred vigorously down and is slowly added dropwise
40% sodium hydroxide solution 20 mL, stratification, divides and takes organic facies, be warming up to after washing 2 times with saturated nacl aqueous solution 130mL
65 DEG C-70 DEG C, ((0.8 g), stirs 30 min, filters, filtrate reduced in volume, obtains for addition kieselguhr (0.8 g) and activated carbon
Brownish red dope S-2(25.38 g, 71.0%, purity 98.2%).
The preparation (S-4) of embodiment 2 (E)-4-bromomethyl methyl cinnamate and (E)-3-[4-[[2-(2-methyl isophthalic acid H-Yin
Diindyl-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. hydrochlorate preparation (S-5) by S-3 25.0g, 50 mL DMF, 5
ML anhydrous acetic acid and N-smell for succimide (NBS, 22.4 g) join nitrogen displacement after 100 mL three-necked bottles in, nitrogen
It is heated to 80 DEG C under protection, finishes back flow reaction 4h.Be cooled to room temperature, obtain pale yellow oil S-4(75.1%) DMF molten
Liquid.
20.8 g S-2 and 130 mL dry DMF being joined in 500 mL three-necked bottles after nitrogen displacement, stirring is to clear
Clearly.Nitrogen protection is lower adds 60 mL N mono-diisopropylethylamine (DIPEA), and 30 mins are stirred at room temperature, and dropping is containing as obtained above
Dry DMF 50 mL solution containing enough S-4.Finish room temperature reaction overnight.Reactant liquor is poured in 200 mL water, with 200
ML ethyl acetate is extracted twice, and merges organic facies, washes twice, by nothing with 200mL water and 200mL saturated nacl aqueous solution successively
Aqueous sodium persulfate filters after drying.Filtrate adds 1.0 mol/L ether solution of hydrogen chloride (about 80 mL), filters, filter cake 60mL
Cold methanol washs, the dried khaki solid S-5(16.5 g that obtains, and 71.8%).
The preparation of embodiment 3 LBH589
Add to, in 250 mL three-necked bottles, be cooled to-15 DEG C, be slowly added dropwise successively and contain by 11.6g S-5 and 120 mL absolute methanols
The 60mL methanol solution of 5.8g potassium hydroxide and 2.0 mol/L azanol methanol solution 150 mL, finish equality of temperature and react overnight.Heat up
Reaction 5h is continued to 0 DEG C.Add 2 mol/L potassium hydroxide solutions (about 30 mL), stir 40 min.It is slowly dropped into water 100 mL,
Separate out a small amount of unreacted raw material completely.Filtering, filter cake use water 100 mL washs, and merging filtrate and washing liquid drip 2 mol/L salt
Acid (about 60 mL), to pH 7-8, has solid to separate out.Filtering, filter cake is through 50% cold methanol washing, dried with toluene 50 mL weight
Crystallization, obtains faint yellow solid LBH589 (8.1 g, 77%, purity 98%).
By the final process of this technical scheme, we obtain LBH589 product, product after purification are carried out LC-
MS, HPLC, NMR detect.
Interpretation of result:
As shown in Figure 1, Figure 2, Figure 3 shows, the peak areas obtaining us can be analyzed than 99% reached from LC-MS figure (Fig. 1).
The main purpose that HPLC analyzes is to separate each component in a mixture, and quantifies each component at mixture
Proportion shared by.LBH589 composition proportion content 99% during (Fig. 2) analyzes this medicine from figure.
In hydrogen nuclear magnetic resonance spectrogram (Fig. 3), the number of characteristic peak reflects the kind of hydrogen atom chemical environment in organic molecule;
Therefrom analyze number of hydrogen atoms and meet LBH589 structural formula.
Sum up:
1. from highly purified result it can be shown that first this technical scheme reduces cost solvent selects, simultaneously in reaction
Decrease to some degree in temperature, in the case of next reduces toxicity, and productivity is constant, our purity reaches
More than 98%.
2. analysis reason is in second step course of reaction, and we decrease the process in terms of solvent, and subsequent reactions also needs to
React under DMF solvent, and the reaction being equivalent to two steps is single step reaction, improves the purity of intermediate.
Technical scheme is as follows: the preparation method of a kind of panobinostat (LBH589), including following step
Rapid:
Step one: phenylhydrazine, absolute methanol 4A molecular sieve are added in three-neck flask, adds first after adding the chloro-2 pentanone of 5-
Alcohol;By reacting liquid filtering, filtrate decompression is evaporated off methanol;Again by washing, filtrate reduced in volume after filtration, obtain brownish red thickness
Thing 2-methyltryptamine;
Step 2: join in three-necked bottle by 4-methyl cinnamic acid methyl ester, DMF, glacial acetic acid and NBS, is warming up under nitrogen protection
10 DEG C-170 DEG C reaction 1-7h;Generate pale yellow oil;This process uses DMF+CH3COOH, solvent selects to reduce poison
Property, subsequent reactions also needs to react under DMF solvent, therefore decreases the purity that solvent processes and improves intermediate;
Step 3: 2-methyltryptamine and DMF are added in three-necked bottle, adds and stir from N mono-diisopropylethylamine, add (E)-4-
Bromomethyl methyl cinnamate, dry DMF are reacted;Filter dried for reactant liquor washing;Obtain khaki solid (E)-3-[4-[[2-
(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. hydrochlorate;
Step 4: by (E)-3-[4-[[2-(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. salt
Hydrochlorate and absolute methanol add cooling in three-necked bottle, and dropping contains methanol solution and the reaction of light amine methanol solution of potassium hydroxide;Add
Potassium hydroxide solution stirs;Instill elutriation and go out a small amount of unreacted raw material completely;Filter, drip salt acid for adjusting pH 7-8, have solid
Body separates out;Filtering, filter cake washs through cold methanol, obtains, with recrystallization, the faint yellow solid LBH589 raw material that purity is higher after drying
Medicine.
Using such scheme, the present invention adopts technical solution of the present invention what advantage or beneficial effect, described advantage or useful
Effect is brought by technical solution of the present invention.
First this technical scheme reduces cost on solvent selects, absolute methanol: dehydrated alcohol=20000/ ton: 4000/
Ton.
Decrease to some degree in reaction temperature simultaneously, methanol boiling point 67 DEG C: ethyl alcohol boiling point 78 DEG C, relatively industry are raw
Produce or small operation, equipment requirements is reduced, more preferably operate and cost-effective.
(E)-4-bromomethyl methyl cinnamate building-up process have employed DMF+CH3COOH
1). carbon tetrachloride liver poison is more severe, and in laboratory or production process, suction can cause uncomfortable, has liver, kidney
Serious infringement.Spilling causes pipeline long term accumulation and damaged.The change of solvent largely reduces toxicity, and is easier place
Reason solvent.
2). subsequent reactions also needs to react under DMF solvent, therefore decreases solvent and processes and improve the pure of intermediate
Degree.
3). original scheme does not has purity, and our scheme is in the case of productivity is constant, the also purity of more than 98%.
This preparation method is more economically saved in general, is environment-friendly and low-toxicity, convenient post-treatment.
There is the highest market using value.
It should be noted that above-mentioned each technical characteristic continues to be mutually combined, form various embodiments the most enumerated above,
It is accordingly to be regarded as the scope that description of the invention is recorded;Further, for those of ordinary skills, can add according to the above description
To improve or conversion, and all these modifications and variations all should belong to the protection domain of claims of the present invention.
Claims (1)
1. the preparation method of a panobinostat (LBH589), it is characterised in that comprise the following steps:
Step one: phenylhydrazine, absolute methanol 4A molecular sieve are added in three-neck flask, adds first after adding the chloro-2 pentanone of 5-
Alcohol;By reacting liquid filtering, filtrate decompression is evaporated off methanol;Again by washing, filtrate reduced in volume after filtration, obtain brownish red thickness
Thing 2-methyltryptamine;
Step 2: join in three-necked bottle by 4-methyl cinnamic acid methyl ester, DMF, glacial acetic acid and NBS, is warming up under nitrogen protection
10 DEG C-170 DEG C reaction 1-7h;Generate pale yellow oil;This process uses DMF+CH3COOH, solvent selects to reduce poison
Property, subsequent reactions also needs to react under DMF solvent, therefore decreases the purity that solvent processes and improves intermediate;
Step 3: 2-methyltryptamine and DMF are added in three-necked bottle, adds and stir from N mono-diisopropylethylamine, add (E)-4-
Bromomethyl methyl cinnamate, dry DMF are reacted;Filter dried for reactant liquor washing;Obtain khaki solid (E)-3-[4-[[2-
(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. hydrochlorate;
Step 4: by (E)-3-[4-[[2-(2-Methyl-1H-indole-3-base) ethylamino-] methyl] phenyl] acrylic acid methyl ester. salt
Hydrochlorate and absolute methanol add cooling in three-necked bottle, and dropping contains methanol solution and the reaction of light amine methanol solution of potassium hydroxide;Add
Potassium hydroxide solution stirs;Instill elutriation and go out a small amount of unreacted raw material completely;Filter, drip salt acid for adjusting pH 7-8, have solid
Body separates out;Filtering, filter cake washs through cold methanol, obtains, with recrystallization, the faint yellow solid LBH589 raw material that purity is higher after drying
Medicine.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610019918.XA CN105732467A (en) | 2016-01-13 | 2016-01-13 | Preparation method of panobinostat |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610019918.XA CN105732467A (en) | 2016-01-13 | 2016-01-13 | Preparation method of panobinostat |
Publications (1)
Publication Number | Publication Date |
---|---|
CN105732467A true CN105732467A (en) | 2016-07-06 |
Family
ID=56246254
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610019918.XA Pending CN105732467A (en) | 2016-01-13 | 2016-01-13 | Preparation method of panobinostat |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105732467A (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1450991A (en) * | 2000-09-01 | 2003-10-22 | 诺瓦提斯公司 | Hydroxamate derives useful as deacetylase inhibitors |
-
2016
- 2016-01-13 CN CN201610019918.XA patent/CN105732467A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1450991A (en) * | 2000-09-01 | 2003-10-22 | 诺瓦提斯公司 | Hydroxamate derives useful as deacetylase inhibitors |
Non-Patent Citations (2)
Title |
---|
DANIEL T. GLATZHOFER,ET AL.: "A 1,10-HOFMANN ELIMINATION SYNTHESIS OF A [6.6]PARACYCLOPHANE TETRAENE", 《TETRAHEDRON LETTERS》 * |
刘倩等: "帕比司他的合成", 《中国医药工业杂志》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105541633B (en) | Open-chain chiral crown ether containing ent-beyerane skeleton and preparation and application thereof | |
CN105693691A (en) | New crystal form and preparation method of highly pure trelagliptin | |
RU2650110C2 (en) | Processes for synthesis of 2-amino-4,6-dimethoxybenzamide and other benzamide compounds | |
AU2016232270B2 (en) | Method for producing (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile | |
CN105669651A (en) | Preparation technique of dabigatran methanesulfonate | |
CN108218798B (en) | Preparation method of Apabetalone | |
CN103755635A (en) | Synthesis methods of lorcaserin derivative and salt thereof | |
JP7241682B2 (en) | Method for preparing deuterated imidazolidinedione compounds | |
CN105712919A (en) | Application of amide condensing agent in vildagliptin synthetic method | |
CA2889650A1 (en) | Process and intermediates for preparing lacosamide | |
RU2708243C1 (en) | Method of producing a phenylalanine compound | |
CN105732467A (en) | Preparation method of panobinostat | |
CN106008392B (en) | A kind of preparation method of the intermediate of cancer therapy drug Dasatinib | |
RU2709493C1 (en) | Method of producing roxadustat | |
CN103755636A (en) | Method for synthesizing Lorcaserin raceme derivative | |
CN112979577A (en) | Preparation method of oxadiazole derivative | |
CN103613513B (en) | Milnacipran hydrochloride intermediate and its preparation method and application | |
CN109232254B (en) | Synthesis method and application of compound | |
CN102702175A (en) | Preparation method of indole-3-succinimide | |
CN107353266B (en) | A kind of preparation method that olefin(e) acid bromine lactonizes | |
CN112125889A (en) | Preparation method of 7-bromo-2- (1-methyl-1H-pyrazol-4-yl) quinoxaline | |
CN104356126A (en) | Preparation method of arotinolol hydrochloride | |
CN111527069A (en) | Quinoline derivatives | |
CN103539796A (en) | Preparation method of levo praziquantel as well as intermediate thereof | |
CN104151299B (en) | Compound, crystal-form compound and preparation method thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
DD01 | Delivery of document by public notice |
Addressee: SHENZHEN KANGLISHENG BIOLOGICAL TECHNOLOGY CO., LTD. Patent person in charge Document name: Notification of Passing Examination on Formalities |
|
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160706 |