CN110183357A - It is a kind of to be used to prepare preparation method of the Sha Ku than bent intermediate - Google Patents
It is a kind of to be used to prepare preparation method of the Sha Ku than bent intermediate Download PDFInfo
- Publication number
- CN110183357A CN110183357A CN201910512180.4A CN201910512180A CN110183357A CN 110183357 A CN110183357 A CN 110183357A CN 201910512180 A CN201910512180 A CN 201910512180A CN 110183357 A CN110183357 A CN 110183357A
- Authority
- CN
- China
- Prior art keywords
- compound
- solution
- added
- methyl
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/04—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid halides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/001—Amines; Imines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (8)
- The compound as shown in formula I (R)-tert-butyl 1. (1- ((1,1 '-biphenyl) -4- base) -3- hydroxy propane -2- base) carbamic acid The preparation method of ester, the reaction mechanism mechanism of reaction such as formula 3, it may be assumed that(1) be starting material with compound 4- Phenylbenzoic acid 25, with acyl halide reagent or under alkaline condition with chloro-carbonic acid Ester reacts in non-protonic solvent obtains compound 26, in which: the acyl halide reagent is halogenation sulfoxide, oxalyl halogen, three Any one of chlorethoxyfos, phosphorus pentachloride, mesyl chloride, aryl sulfonyl chloride or trifluoromethanesulfchloride chloride;R is halogen or sulphonic acid ester Base or methyl carbonic acid ester group or alkylcarbonic acid ester group or arylcarbonic acid ester group less than six carbon;The alkali is three second Amine, diisopropyl ethyl amine, N-methylmorpholine, pyridine or triethylene diamine (DABCO), 1,8- diazabicyclo [5,4,0] 11 carbon -7- alkene (DBU), 1,5- diazabicyclo [4,3,0] nonyl- 5- alkene (DBN) either 4-dimethylaminopyridine or tetramethyl Any one of base ethylenediamine: the non-protonic solvent is any of methylene chloride or methyl tertiary butyl ether(MTBE) or toluene Any combination of kind or above-mentioned solvent;(2) through micro passage reaction Wollf rearrangement reaction is occurred for the methyl tertiary butyl ether(MTBE) of compound 26 and diazomethane to obtain Compound 27;(3) compound 27 is reacted in non-protonic solvent with acyl halide reagent or under alkaline condition with chloro-formate To compound 28, the alkaline condition refers to triethylamine, diisopropyl ethyl amine, N-methylmorpholine, pyridine or triethylene Diamines (DABCO), the 11 carbon -7- alkene (DBU) of 1,8- diazabicyclo [5,4,0], 1,5- diazabicyclo [4,3,0] nonyl- 5- Alkene (DBN) alkaline condition that either any one of 4-dimethylaminopyridine or tetramethylethylenediamine are constituted;(4) through micro passage reaction Wollf rearrangement reaction is occurred into for compound 28 with diazomethane again and obtains chlorine ketone compound 29;(5) compound 29 is converted under alkaline condition and obtains compound 30, in which: the alkali be alkali metal hydroxide or Alkaline earth metal hydroxide or alkali metal formate or alkaline-earth metal formates or alkali metal acetate or alkaline-earth metal acetic acid Any one of salt;(6) compound 30 is obtained into compound 12 through aminopherase enzymic catalytic reaction highly-solid selectively;(7) compound 12 is reacted under alkaline condition to obtain compound 2 with di-tert-butyl dicarbonate, the alkali is alkali metal Carbonate, alkali metal hydrogencarbonate, alkali metal hydroxide, alkaline earth metal hydroxide, pyridine, triethylamine, diisopropyl second Any one of base amine, 4-dimethylaminopyridine, N-methylmorpholine or tetramethylethylenediamine.
- 2. being used to prepare preparation method of the Sha Ku than bent midbody compound 2 as described in claim 1, it is characterised in that:Step (1) is into (5): the acyl halide reagent is thionyl chloride, and the alkyl for being less than six carbon includes: methyl, second Any one of base, n-propyl, isopropyl, normal-butyl, isobutyl group and tert-butyl, R are halogen or sulfonate group or methyl Carbonate group or alkylcarbonic acid ester group less than six carbon or arylcarbonic acid ester group are chlorine, ethyl carbonate ester group or isobutyl group Carbonate group it is any, the alkali be triethylamine, diisopropyl ethyl amine or N-methylmorpholine it is any;The polar solvent that the conversion in polar solvent obtains compound 30 under alkaline condition of compound 29 is N, N- in step (5) Dimethylformamide, N-Methyl pyrrolidone, low alkyl group alcohols solvent or water, alkali are sodium hydroxide, potassium hydroxide, hydrogen-oxygen Change any one of barium, potassium carbonate, sodium formate or sodium acetate.
- 3. according to claim 1 or 2 be used to prepare preparation method of the Sha Ku than bent midbody compound 2, feature exists Preferred alkali is potassium carbonate or sodium hydroxide in step (7).
- 4. according to claim 3 be used to prepare preparation method of the Sha Ku than bent midbody compound 2, it is characterised in that: The preparation of the t-butyl methyl ether solution of diazomethane in step (3) and (4) are as follows: by methyl tertiary butyl ether(MTBE) and diethylene glycol two Methyl ether stirs evenly after methyl-nitroso-urea is added in the case where ice-water bath is cooling, then by the solution and weight ratio of methyl-nitroso-urea It is prepared by weight 3:1 through micro passage reaction for 30% potassium hydroxide solution, obtains the methyl tertiary butyl ether(MTBE) of diazomethane Solution, by the t-butyl methyl ether solution of the solution of compound 26 and diazomethane by weight 1:1 through micro passage reaction system Standby diazonium compound, flows into water, is slowly heated to 60 DEG C, is stirred to react 1 hour, stratification, and organic phase is concentrated under reduced pressure, remaining Methylene chloride is added in object, under ice-water bath is cooling, thionyl chloride is added dropwise, removes cryostat after dripping off, is warming up to back flow reaction 2 hours, It is cooled to room temperature to obtain the solution of compound 28, then the t-butyl methyl ether solution of the solution of compound 28 and diazomethane is pressed Weight ratio 1:1 prepares diazonium compound through micro passage reaction, flows into hydrochloric acid, and ice-water bath is cooling, is stirred to react 1 hour.It stands Layering, organic phase are concentrated under reduced pressure, and residue directly casts single step reaction.
- 5. according to claim 4 be used to prepare preparation method of the Sha Ku than bent midbody compound 2, it is characterised in that Alkali used in step (5) is sodium hydroxide.
- 6. according to claim 5 be used to prepare preparation method of the Sha Ku than bent midbody compound 2, it is characterised in that Alkali used in step (7) is potassium carbonate.
- 7. according to claim 3 be used to prepare preparation method of the Sha Ku than bent midbody compound 2, it is characterised in that: The preparation of the t-butyl methyl ether solution of diazomethane in step (3) and (4) are as follows: by methyl tertiary butyl ether(MTBE) and diethylene glycol two Methyl ether stirs evenly after methyl-nitroso-urea is added in the case where ice-water bath is cooling, then by the solution and weight ratio of methyl-nitroso-urea It is prepared by weight 3:1 through micro passage reaction for 30% potassium hydroxide solution, obtains the methyl tertiary butyl ether(MTBE) of diazomethane Solution, by the t-butyl methyl ether solution of the solution of compound 26 and diazomethane by weight 1:1 through micro passage reaction system Standby diazonium compound, flows into water, is slowly heated to 60 DEG C, is stirred to react 1 hour, stratification, and organic phase is concentrated under reduced pressure, remaining Methylene chloride is added in object, under ice-water bath is cooling, triethylamine is added dropwise, temperature control -5~0 DEG C is added dropwise ethyl chloroformate, keeps the temperature after dripping off It is stirred to react 1 hour, filters, obtain the solution of compound 28, the solution of compound 28 and the methyl tertiary butyl ether(MTBE) of diazomethane Solution prepares diazonium compound through micro passage reaction by weight 1:1, flows into hydrochloric acid, and ice-water bath is cooling, and it is small to be stirred to react 1 When, stratification, organic phase is concentrated under reduced pressure, and n,N-Dimethylformamide, sodium formate are added in the residue after concentration, is heated to It 90 DEG C, is stirred to react 5 hours, is cooled to room temperature, 100mL hydrochloric acid is added, continue to be heated to 100 DEG C of stirrings 1 hour, be cooled to room Solid product is precipitated in temperature, and filtering obtains compound 30, and polyethylene glycol is added in compound 30, stirs 10 minutes, and pH=8.0 is added Phosphate buffer, isopropylamine, phosphopyridoxal pyridoxal phosphate and transaminase, 45 DEG C insulated and stirred 20 hours.With sodium hydroxide solution tune PH to 10 or more filters to obtain crude product, and second alcohol and water is added in crude product, and system is warming up to 45~50 DEG C, stirs 30min, and temperature control is added dropwise Di-tert-butyl dicarbonate and sodium hydroxide solution, control system pH=9~10 drip off rear insulation reaction 3 hours.Second is recovered under reduced pressure Alcohol is cooled to room temperature, and filtering obtains product 2.
- 8. according to claim 3 be used to prepare preparation method of the Sha Ku than bent midbody compound 2, it is characterised in that: The preparation of the t-butyl methyl ether solution of diazomethane in step (3) and (4) are as follows: by methyl tertiary butyl ether(MTBE) and diethylene glycol two Methyl ether stirs evenly after methyl-nitroso-urea is added in the case where ice-water bath is cooling, then by the solution and weight ratio of methyl-nitroso-urea It is prepared by weight 3:1 through micro passage reaction for 30% potassium hydroxide solution, obtains the methyl tertiary butyl ether(MTBE) of diazomethane Solution, by the t-butyl methyl ether solution of the solution of compound 26 and diazomethane by weight 1:1 through micro passage reaction system Standby diazonium compound, flows into water, is slowly heated to 60 DEG C, is stirred to react 1 hour, stratification, and organic phase is concentrated under reduced pressure, remaining Methylene chloride is added in object, under ice-water bath is cooling, N-methylmorpholine is added dropwise, temperature control -10~-5 DEG C are added dropwise isobutyl chlorocarbonate, drip off The solution of compound 28 is obtained by filtration in insulation reaction 30 minutes afterwards, by the methyl- tert fourth of the solution of compound 28 and diazomethane Base ethereal solution prepares diazonium compound through micro passage reaction by weight 1:1, flows into hydrochloric acid, and ice-water bath is cooling, is stirred to react 1 Hour, stratification, organic phase is concentrated under reduced pressure, and water and potassium hydroxide are added into the residue after concentration, is heated to slightly boiled, stirs Reaction 8 hours is mixed, room temperature is cooled to, is extracted with dichloromethane, separate organic phase, recrystallized after concentration with methyl tertiary butyl ether(MTBE), Compound 30, compound 30 and polyethylene glycol are obtained, stirs 10 minutes, the phosphate buffer, isopropylamine, phosphorus of pH=8 is added Sour pyridoxal and transaminase, 45 DEG C insulated and stirred 20 hours, then with sodium hydroxide solution tune pH to 10 or more, filter to obtain crude product, It is obtained by filtration in crude product in upper step and water and ethyl alcohol is added, be warming up to 40~50 DEG C, stir 30min dissolved clarification, triethylamine is added dropwise, slowly It is down to room temperature, di-tert-butyl dicarbonate is added dropwise, drips off rear insulation reaction 5 hours, ethyl alcohol is recovered under reduced pressure, is cooled to room temperature, is filtered, Obtain product 2.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910512180.4A CN110183357B (en) | 2019-06-13 | 2019-06-13 | Preparation method for preparing Sacubitril intermediate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910512180.4A CN110183357B (en) | 2019-06-13 | 2019-06-13 | Preparation method for preparing Sacubitril intermediate |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110183357A true CN110183357A (en) | 2019-08-30 |
CN110183357B CN110183357B (en) | 2021-09-24 |
Family
ID=67721553
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910512180.4A Active CN110183357B (en) | 2019-06-13 | 2019-06-13 | Preparation method for preparing Sacubitril intermediate |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110183357B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112679404A (en) * | 2020-12-30 | 2021-04-20 | 杭州科巢生物科技有限公司 | Method for synthesizing Upactinib chiral intermediate by using microchannel reaction technology |
CN113754565A (en) * | 2021-11-09 | 2021-12-07 | 南京威凯尔生物医药科技有限公司 | Method for preparing Shakubaqu intermediate in continuous flow microreactor |
CN115745841A (en) * | 2021-09-03 | 2023-03-07 | 凯特立斯(深圳)科技有限公司 | Preparation method of shakubiqu intermediate |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007009083A2 (en) * | 2005-07-12 | 2007-01-18 | Acadia Pharmaceuticals Inc. | Compounds with activity at retinoic acid receptors |
WO2010081410A1 (en) * | 2009-01-13 | 2010-07-22 | Zhejiang Jiuzhou Pharmaceutical Co., Ltd. | Process for manufacture and resolution of 2-acylamino-3-diphenylpropanoic acid |
WO2014032627A1 (en) * | 2012-08-31 | 2014-03-06 | Zhejiang Jiuzhou Pharmaceutical Co., Ltd | New process |
CN105168205A (en) * | 2015-08-18 | 2015-12-23 | 泰力特医药(湖北)有限公司 | Preparation method for dual inhibitor LCZ696 of angiotensin II receptor and neprilysin |
CN105330569A (en) * | 2015-09-11 | 2016-02-17 | 天台宜生生化科技有限公司 | Preparation method of (R)-2-(N-tertbutyloxycarbonylamino)biphenylpropanol |
CN105601524A (en) * | 2016-03-17 | 2016-05-25 | 海门慧聚药业有限公司 | Preparation method of LCZ696 key intermediate |
CN105985225A (en) * | 2015-02-12 | 2016-10-05 | 博瑞生物医药(苏州)股份有限公司 | Preparation methods for LCZ-696 and intermediate thereof |
WO2017148357A1 (en) * | 2016-02-29 | 2017-09-08 | 广东东阳光药业有限公司 | Sacubitril intermediate and preparation method thereof |
CN107382779A (en) * | 2017-07-27 | 2017-11-24 | 江苏中邦制药有限公司 | One planting sand storehouse must bent intermediate preparation method |
CN108675943A (en) * | 2018-06-13 | 2018-10-19 | 常州亚邦制药有限公司 | The preparation method of one planting sand library Ba Qu key intermediates |
-
2019
- 2019-06-13 CN CN201910512180.4A patent/CN110183357B/en active Active
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007009083A2 (en) * | 2005-07-12 | 2007-01-18 | Acadia Pharmaceuticals Inc. | Compounds with activity at retinoic acid receptors |
WO2010081410A1 (en) * | 2009-01-13 | 2010-07-22 | Zhejiang Jiuzhou Pharmaceutical Co., Ltd. | Process for manufacture and resolution of 2-acylamino-3-diphenylpropanoic acid |
WO2014032627A1 (en) * | 2012-08-31 | 2014-03-06 | Zhejiang Jiuzhou Pharmaceutical Co., Ltd | New process |
CN105985225A (en) * | 2015-02-12 | 2016-10-05 | 博瑞生物医药(苏州)股份有限公司 | Preparation methods for LCZ-696 and intermediate thereof |
CN105168205A (en) * | 2015-08-18 | 2015-12-23 | 泰力特医药(湖北)有限公司 | Preparation method for dual inhibitor LCZ696 of angiotensin II receptor and neprilysin |
CN105330569A (en) * | 2015-09-11 | 2016-02-17 | 天台宜生生化科技有限公司 | Preparation method of (R)-2-(N-tertbutyloxycarbonylamino)biphenylpropanol |
WO2017148357A1 (en) * | 2016-02-29 | 2017-09-08 | 广东东阳光药业有限公司 | Sacubitril intermediate and preparation method thereof |
CN105601524A (en) * | 2016-03-17 | 2016-05-25 | 海门慧聚药业有限公司 | Preparation method of LCZ696 key intermediate |
CN107382779A (en) * | 2017-07-27 | 2017-11-24 | 江苏中邦制药有限公司 | One planting sand storehouse must bent intermediate preparation method |
CN108675943A (en) * | 2018-06-13 | 2018-10-19 | 常州亚邦制药有限公司 | The preparation method of one planting sand library Ba Qu key intermediates |
Non-Patent Citations (1)
Title |
---|
王艳: "LCZ696合成工艺探讨", 《中国优秀硕士学位论文 工程科技I辑》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112679404A (en) * | 2020-12-30 | 2021-04-20 | 杭州科巢生物科技有限公司 | Method for synthesizing Upactinib chiral intermediate by using microchannel reaction technology |
CN115745841A (en) * | 2021-09-03 | 2023-03-07 | 凯特立斯(深圳)科技有限公司 | Preparation method of shakubiqu intermediate |
WO2023029235A1 (en) * | 2021-09-03 | 2023-03-09 | 凯特立斯(深圳)科技有限公司 | Method for preparing sacubitril intermediate |
CN115745841B (en) * | 2021-09-03 | 2024-04-16 | 凯特立斯(深圳)科技有限公司 | Preparation method of sakubi-qu intermediate |
CN113754565A (en) * | 2021-11-09 | 2021-12-07 | 南京威凯尔生物医药科技有限公司 | Method for preparing Shakubaqu intermediate in continuous flow microreactor |
Also Published As
Publication number | Publication date |
---|---|
CN110183357B (en) | 2021-09-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111423452B (en) | Intermediate of Rayleigh Lu Geli and preparation method and application thereof | |
CN110183357A (en) | It is a kind of to be used to prepare preparation method of the Sha Ku than bent intermediate | |
CN101538228B (en) | Method for synthesizing medical compound peramivir for resisting influenza viruses and avian influenza viruses | |
CN103524383B (en) | Method for preparing peramivir | |
EP3828170A1 (en) | Method for safely preparing pimavanserin and tartrate salt thereof using triphosgene | |
CN103570580B (en) | Preparation method of high-purity iopromide | |
CN102746210A (en) | Synthesis method for key intermediate of silodosin | |
CN102617542B (en) | Method for preparing and purifying olmesartan intermediate | |
CN106699570A (en) | Synthesis method for (2-chloro-5-iodophenyl)(4-fluorophenyl)ketone | |
CN108467355A (en) | (R) preparation method of-Esomeprazole | |
CN103396406B (en) | Preparation method of candesartan cilexetil | |
CN116514704B (en) | Rafenacin intermediate and preparation method thereof | |
CN106699604B (en) | One seed sand library is than bent and its intermediate preparation method | |
CN103717580A (en) | Method for preparing amino-triazolinone | |
WO2015123998A1 (en) | Method for synthesizing vildagliptin | |
CN101585778B (en) | Lyrica preparation method | |
GB2451384A (en) | 2-cyanophenylboronic acid with reduced impurities or ester thereof,and production method thereof | |
JP2011042647A (en) | Method for producing optically active nipecotamide | |
CN101298448B (en) | Synthetic method of 2-benzyloxy-3-ethyl-4-methyl-5-chloro-6-[(tetrahydro-2H-pyrrole-2-oxyl)methyl ] phenol | |
CN101302195B (en) | Novel synthetic method of 7-hydroxy-3,4-dihydroquinolines | |
WO2006080401A1 (en) | Method for producing fluorinated proline derivative | |
CN102093292A (en) | Method for synthesizing DL-alpha-aminocaprolactam | |
EP4063349A1 (en) | Method for producing pyrrolidine compound | |
CN104610215A (en) | Preparation method of nebivolol intermediates and preparation method of nebivolol | |
CN102336676A (en) | New preparation method of dopexamine hydrochloride by ArCHR protection strategy |
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 | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method for preparing intermediate of shakubiqu Effective date of registration: 20220429 Granted publication date: 20210924 Pledgee: Bank of China Limited Baiyin branch Pledgor: GANSU HAOTIAN PHARMA TECH Co.,Ltd. Registration number: Y2022620000012 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230526 Granted publication date: 20210924 Pledgee: Bank of China Limited Baiyin branch Pledgor: GANSU HAOTIAN PHARMA TECH Co.,Ltd. Registration number: Y2022620000012 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method for preparing intermediate of Shakubiqu Effective date of registration: 20230607 Granted publication date: 20210924 Pledgee: Bank of China Limited Baiyin branch Pledgor: GANSU HAOTIAN PHARMA TECH Co.,Ltd. Registration number: Y2023980043274 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |