CN116283635A - A method for synthesizing N,3,3-trimethyl-2-oxobutanamide - Google Patents
A method for synthesizing N,3,3-trimethyl-2-oxobutanamide Download PDFInfo
- Publication number
- CN116283635A CN116283635A CN202211732114.6A CN202211732114A CN116283635A CN 116283635 A CN116283635 A CN 116283635A CN 202211732114 A CN202211732114 A CN 202211732114A CN 116283635 A CN116283635 A CN 116283635A
- Authority
- CN
- China
- Prior art keywords
- trimethyl
- oxobutanamide
- synthesizing
- dimethyl
- oxo
- 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
- 238000000034 method Methods 0.000 title claims abstract description 20
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 13
- BLDDQHZFVPZNLF-UHFFFAOYSA-N n,3,3-trimethyl-2-oxobutanamide Chemical compound CNC(=O)C(=O)C(C)(C)C BLDDQHZFVPZNLF-UHFFFAOYSA-N 0.000 title description 22
- IAWVHZJZHDSEOC-UHFFFAOYSA-N 3,3-dimethyl-2-oxobutanoic acid Chemical compound CC(C)(C)C(=O)C(O)=O IAWVHZJZHDSEOC-UHFFFAOYSA-N 0.000 claims abstract description 10
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 150000007530 organic bases Chemical class 0.000 claims abstract description 9
- 238000006482 condensation reaction Methods 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 22
- 239000003960 organic solvent Substances 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 2
- GPDHNZNLPKYHCN-DZOOLQPHSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-morpholin-4-ylmethylidene]-dimethylazanium;hexafluorophosphate Chemical group F[P-](F)(F)(F)(F)F.CCOC(=O)C(\C#N)=N/OC(=[N+](C)C)N1CCOCC1 GPDHNZNLPKYHCN-DZOOLQPHSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 17
- 238000001308 synthesis method Methods 0.000 abstract description 4
- 230000007613 environmental effect Effects 0.000 abstract 1
- 231100000086 high toxicity Toxicity 0.000 abstract 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- -1 (diphenylphosphino)-2-[(diphenylphosphino)oxy]-3,3,N-trimethylbutanamide Chemical compound 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000001394 phosphorus-31 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N N,N′-Dicyclohexylcarbodiimide Substances C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
技术领域technical field
本发明涉及酰胺类技术领域，尤其涉及一种合成N,3,3-三甲基-2-氧代丁酰胺的方法。The invention relates to the technical field of amides, in particular to a method for synthesizing N,3,3-trimethyl-2-oxobutyramide.
背景技术Background technique
N,3,3-三甲基-2-氧代丁酰胺(3)，英文名N,3,3-trimethyl-2-oxobutanamide，是合成高效不对称氢化反应中应用的tLANOP配体(N-(二苯基膦基)-2-[(二苯基膦基)氧]-3，3，N-三甲基丁酰胺)膦配体的关键中间体。文献High yield acyl anion trappingreactions:direct nucleophilic acylation of isocyanates and isothiocyanates.(Tetrahedron:Asymmetry 1998,9,4043–4054)公开了如下图的合成方法：N,3,3-trimethyl-2-oxobutanamide (3), English name N,3,3-trimethyl-2-oxobutanamide, is a tLANOP ligand (N- Key intermediate of (diphenylphosphino)-2-[(diphenylphosphino)oxy]-3,3,N-trimethylbutanamide)phosphine ligand. The document High yield acyl anion trapping reactions:direct nucleophilic acylation of isocyanates and isothiocyanates. (Tetrahedron:
已有的合成N,3,3-三甲基-2-氧代丁酰胺的文献和专利很少(TetrahedronLetters(1984),25(46),5251-4.；EP0798289A1)。具体的合成方法如下图：There are few literatures and patents on the synthesis of N,3,3-trimethyl-2-oxobutanamide (Tetrahedron Letters (1984), 25 (46), 5251-4.; EP0798289A1). The specific synthesis method is as follows:
在这种方法中，以高危险性的叔丁醇锂，高毒性的一氧化碳和活性的异氰酸酯为原料，在-110℃的低温条件下，以84％的收率合成了N,3,3-三甲基-2-氧代丁酰胺。应用高活性，高毒性的原料和超低温的条件，明显限制了该方法的广泛应用。尽管目前合成酰胺的手段多种多样，但是到目前为止，还没有一种温和高效的方法来合成N,3,3-三甲基-2-氧代丁酰胺这一重要的化合物。In this method, N,3,3-N,3,3- Trimethyl-2-oxobutanamide. The application of highly active, highly toxic raw materials and ultra-low temperature conditions obviously limit the wide application of this method. Although there are many ways to synthesize amides, so far, there is no mild and efficient method to synthesize N,3,3-trimethyl-2-oxobutyramide, an important compound.
发明内容Contents of the invention
针对现有技术中所存在的不足，本发明提供了一种合成N,3,3-三甲基-2-氧代丁酰胺的方法，其解决了现有技术中存在的高毒性的原料和超低温的条件导致方法应用受限的问题。Aiming at the deficiencies in the prior art, the invention provides a method for synthesizing N,3,3-trimethyl-2-oxobutyramide, which solves the problems of highly toxic raw materials and The ultra-low temperature condition leads to the problem of limited application of the method.
本发明一方面，提供一种合成N,3,3-三甲基-2-氧代丁酰胺的方法，以3,3-二甲基-2-氧代丁酸为原料，在有机碱和缩合剂作用下，与甲胺盐酸盐发生缩合反应，生成N,3,3-三甲基-2-氧代丁酰胺。One aspect of the present invention provides a method for synthesizing N,3,3-trimethyl-2-oxobutyramide, using 3,3-dimethyl-2-oxobutyric acid as a raw material in an organic base and Under the action of a condensing agent, it undergoes a condensation reaction with methylamine hydrochloride to generate N,3,3-trimethyl-2-oxobutyramide.
进一步地，该方法包括以下步骤：Further, the method includes the following steps:
S1：将3,3-二甲基-2-氧代丁酸溶解于有机溶剂中；S1: dissolving 3,3-dimethyl-2-oxobutanoic acid in an organic solvent;
S2：加入甲胺盐酸盐、有机碱和缩合剂，进行缩合反应。S2: adding methylamine hydrochloride, an organic base and a condensation agent to carry out condensation reaction.
进一步地，所述3,3-二甲基-2-氧代丁酸与有机溶剂的摩尔体积比为1:10-30。Further, the molar volume ratio of the 3,3-dimethyl-2-oxobutanoic acid to the organic solvent is 1:10-30.
进一步地，3,3-二甲基-2-氧代丁酸、甲胺盐酸盐、缩合剂、有机碱的摩尔比为1:2:2:1.21。Further, the molar ratio of 3,3-dimethyl-2-oxobutanoic acid, methylamine hydrochloride, condensing agent, and organic base is 1:2:2:1.21.
进一步地，所述有机碱为N-甲基吗啡啉。Further, the organic base is N-methylmorpholine.
进一步地，所述缩合剂为COMU。Further, the condensing agent is COMU.
进一步地，所用有机溶剂为二氯甲烷。Further, the organic solvent used is dichloromethane.
进一步地，缩合反应的温度为20-35℃，反应时间为9-12小时。Further, the temperature of the condensation reaction is 20-35° C., and the reaction time is 9-12 hours.
本文中术语“eq”或“equiv.”为摩尔当量，“V”为溶剂体积，比如10V代表溶剂体积为溶质摩尔当量的10倍，每摩尔对应每升。具体来说3，3-二甲基-2-羰基丁酸的摩尔当量为1eq.，二氯甲烷用量为10V，浓度为0.1mol/L。Herein, the term "eq" or "equiv." refers to the molar equivalent, and "V" refers to the volume of the solvent. For example, 10V means that the volume of the solvent is 10 times the molar equivalent of the solute, and each mole corresponds to each liter. Specifically, the molar equivalent of 3,3-dimethyl-2-oxobutanoic acid is 1 eq., the amount of methylene chloride is 10 V, and the concentration is 0.1 mol/L.
相比于现有技术，本发明具有如下有益效果：Compared with the prior art, the present invention has the following beneficial effects:
1)本发明的合成方法生成的N,3,3-三甲基-2-氧代丁酰胺的收率高，收率达到82％。1) The yield of N,3,3-trimethyl-2-oxobutyramide produced by the synthesis method of the present invention is high, and the yield reaches 82%.
2)本发明的反应条件温和，适合放大生产。2) The reaction conditions of the present invention are mild and suitable for scale-up production.
3)本发明安全环保，没有采用高毒性的原料。3) The present invention is safe and environment-friendly, and does not use highly toxic raw materials.
附图说明Description of drawings
图1为本发明实施例1中N,3,3-三甲基-2-氧代丁酰胺的1H-NMR图谱。Figure 1 is the 1 H-NMR spectrum of N,3,3-trimethyl-2-oxobutyramide in Example 1 of the present invention.
图2为本发明实施例1中N,3,3-三甲基-2-氧代丁酰胺的31P-NMR图谱。Fig. 2 is the 31 P-NMR spectrum of N,3,3-trimethyl-2-oxobutyramide in Example 1 of the present invention.
具体实施方式Detailed ways
下面结合附图及实施例对本发明中的技术方案进一步说明。The technical solutions in the present invention will be further described below in conjunction with the accompanying drawings and embodiments.
实施例1N,3,3-三甲基-2-氧代丁酰胺的制备Embodiment 1N, the preparation of 3,3-trimethyl-2-oxobutanamide
室温下，向溶于二氯甲烷(15V)的3，3-二甲基-2-羰基丁酸(1eq)的反应液中依次缓慢加入N-甲基吗啡啉(2eq)，甲胺盐酸盐(2eq)和(2-肟基-氰基乙酸乙酯)-N,N-二甲基-吗啉基脲六氟磷酸酯(COMU)(1.21eq)，反应液在室温下搅拌10小时。即可分离得到82％的终产物N,3,3-trimethyl-2-oxobutanamide(3)。终产物的1H-NMR和31P-NMR图谱如图1、2所示。反应式如下所示：At room temperature, slowly add N-methylmorpholine (2eq), methylamine hydrochloride to the reaction solution of 3,3-dimethyl-2-carbonylbutanoic acid (1eq) dissolved in dichloromethane (15V) Salt (2eq) and (2-oximino-ethyl cyanoacetate)-N,N-dimethyl-morpholinourea hexafluorophosphate (COMU) (1.21eq), the reaction solution was stirred at room temperature for 10 hours . That is to say, 82% of the final product N,3,3-trimethyl-2-oxobutanamide (3) can be isolated. The 1 H-NMR and 31 P-NMR spectra of the final product are shown in Figures 1 and 2 . The reaction formula is as follows:
实施例2N,3,3-三甲基-2-氧代丁酰胺的制备Embodiment 2N, the preparation of 3,3-trimethyl-2-oxobutanamide
室温下，向溶于二氯甲烷(10V)的3，3-二甲基-2-羰基丁酸(1eq)的反应液中依次缓慢加入N-甲基吗啡啉(2eq)，甲胺盐酸盐(2eq)和(2-肟基-氰基乙酸乙酯)-N,N-二甲基-吗啉基脲六氟磷酸酯(COMU)(1.21eq)，反应液在20℃下搅拌12小时。即可分离得到80％的终产物N,3,3-trimethyl-2-oxobutanamide(3)。At room temperature, slowly add N-methylmorpholine (2eq), methylamine hydrochloride to the reaction solution of 3,3-dimethyl-2-carbonylbutanoic acid (1eq) dissolved in dichloromethane (10V) Salt (2eq) and (2-oximino-ethyl cyanoacetate)-N,N-dimethyl-morpholinourea hexafluorophosphate (COMU) (1.21eq), the reaction solution was stirred at 20°C for 12 Hour. Then 80% of the final product N,3,3-trimethyl-2-oxobutanamide (3) can be isolated.
实施例3N,3,3-三甲基-2-氧代丁酰胺的制备Embodiment 3N, the preparation of 3,3-trimethyl-2-oxobutanamide
室温下，向溶于二氯甲烷(30V)的3，3-二甲基-2-羰基丁酸(1eq)的反应液中依次缓慢加入N-甲基吗啡啉(2eq)，甲胺盐酸盐(2eq)和(2-肟基-氰基乙酸乙酯)-N,N-二甲基-吗啉基脲六氟磷酸酯(COMU)(1.21eq)，反应液在35℃下搅拌9小时。即可分离得到77％的终产物N,3,3-trimethyl-2-oxobutanamide(3)。At room temperature, slowly add N-methylmorpholine (2eq), methylamine hydrochloride to the reaction solution of 3,3-dimethyl-2-carbonylbutanoic acid (1eq) dissolved in dichloromethane (30V) salt (2eq) and (2-oximino-ethyl cyanoacetate)-N,N-dimethyl-morpholinourea hexafluorophosphate (COMU) (1.21eq), the reaction solution was stirred at 35°C for 9 Hour. 77% of the final product N,3,3-trimethyl-2-oxobutanamide (3) can be isolated.
对比例1N,3,3-三甲基-2-氧代丁酰胺的制备Comparative example 1N, the preparation of 3,3-trimethyl-2-oxobutyramide
与实施例1类似，不同之处在于：将COMU替换为EDCI和HOBt，将N-甲基吗啡啉替换为DIPEA，并调整最佳配比和反应温度，反应式如下：Similar to Example 1, the difference is: COMU is replaced by EDCI and HOBt, N-methylmorpholine is replaced by DIPEA, and the optimum proportioning and reaction temperature are adjusted, the reaction formula is as follows:
经检测，N,3,3-三甲基-2-氧代丁酰胺的收率小于15％。After testing, the yield of N,3,3-trimethyl-2-oxobutanamide is less than 15%.
对比例2N,3,3-三甲基-2-氧代丁酰胺的制备Comparative Example 2N, the preparation of 3,3-trimethyl-2-oxobutyramide
与实施例1类似，不同之处在于：将COMU替换为DCC和HOBt，将N-甲基吗啡啉替换为DIPEA，将DCM替换为THF，并调整最佳配比和反应温度，反应式如下：Similar to Example 1, the difference is that COMU is replaced by DCC and HOBt, N-methylmorpholine is replaced by DIPEA, DCM is replaced by THF, and the optimal proportion and reaction temperature are adjusted. The reaction formula is as follows:
经检测，N,3,3-三甲基-2-氧代丁酰胺的收率小于13％。After testing, the yield of N,3,3-trimethyl-2-oxobutanamide is less than 13%.
对比例3N,3,3-三甲基-2-氧代丁酰胺的制备Comparative Example 3N, the preparation of 3,3-trimethyl-2-oxobutyramide
与实施例1类似，不同之处在于：将COMU替换为HATU和HOAT，将N-甲基吗啡啉替换为DIPEA，将DCM替换为DMF，并调整最佳配比和反应温度，反应式如下：Similar to Example 1, the difference is that COMU is replaced by HATU and HOAT, N-methylmorpholine is replaced by DIPEA, DCM is replaced by DMF, and the optimal proportioning and reaction temperature are adjusted. The reaction formula is as follows:
经检测，N,3,3-三甲基-2-氧代丁酰胺的收率小于10％。After testing, the yield of N,3,3-trimethyl-2-oxobutanamide is less than 10%.
对比例4N,3,3-三甲基-2-氧代丁酰胺的制备Comparative example 4N, the preparation of 3,3-trimethyl-2-oxobutyramide
反应式如下：The reaction formula is as follows:
经检测，N,3,3-三甲基-2-氧代丁酰胺的收率小于5％。After detection, the yield of N,3,3-trimethyl-2-oxobutyramide is less than 5%.
最后说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的宗旨和范围，其均应涵盖在本发明的权利要求范围当中。Finally, it is noted that the above embodiments are only used to illustrate the technical solutions of the present invention without limitation. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be carried out Modifications or equivalent replacements without departing from the spirit and scope of the technical solution of the present invention shall be covered by the claims of the present invention.
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211732114.6A CN116283635B (en) | 2022-12-30 | 2022-12-30 | A method for synthesizing N,3,3-trimethyl-2-oxobutyramide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211732114.6A CN116283635B (en) | 2022-12-30 | 2022-12-30 | A method for synthesizing N,3,3-trimethyl-2-oxobutyramide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116283635A true CN116283635A (en) | 2023-06-23 |
| CN116283635B CN116283635B (en) | 2025-04-15 |
Family
ID=86815694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211732114.6A Active CN116283635B (en) | 2022-12-30 | 2022-12-30 | A method for synthesizing N,3,3-trimethyl-2-oxobutyramide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116283635B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101519389A (en) * | 2009-02-19 | 2009-09-02 | 苏州昊帆生物科技有限公司 | Method for preparing N, N-dimethyl-4-morpholine carboxylic acid amide |
| CN106573958A (en) * | 2014-08-07 | 2017-04-19 | 豪夫迈·罗氏有限公司 | Processes for preparation of oxytocin analogues |
| CN107311961A (en) * | 2016-04-26 | 2017-11-03 | 成都巴赛泰德生物科技有限公司 | A kind of reduction COMU synthesis technique |
| WO2022020731A2 (en) * | 2020-07-23 | 2022-01-27 | Life Technologies Corporation | Compositions, systems and methods for biological analysis involving energy transfer dye conjugates and analytes comprising the same |
| WO2022178633A1 (en) * | 2021-02-25 | 2022-09-01 | Mcmaster University | Antibody recruitment molecules and methods of treating covid-19 using same |
-
2022
- 2022-12-30 CN CN202211732114.6A patent/CN116283635B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101519389A (en) * | 2009-02-19 | 2009-09-02 | 苏州昊帆生物科技有限公司 | Method for preparing N, N-dimethyl-4-morpholine carboxylic acid amide |
| CN106573958A (en) * | 2014-08-07 | 2017-04-19 | 豪夫迈·罗氏有限公司 | Processes for preparation of oxytocin analogues |
| CN107311961A (en) * | 2016-04-26 | 2017-11-03 | 成都巴赛泰德生物科技有限公司 | A kind of reduction COMU synthesis technique |
| WO2022020731A2 (en) * | 2020-07-23 | 2022-01-27 | Life Technologies Corporation | Compositions, systems and methods for biological analysis involving energy transfer dye conjugates and analytes comprising the same |
| WO2022178633A1 (en) * | 2021-02-25 | 2022-09-01 | Mcmaster University | Antibody recruitment molecules and methods of treating covid-19 using same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116283635B (en) | 2025-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111072660B (en) | Simple preparation method of rilibatan | |
| WO2004007449A1 (en) | Process for conversion of phenols to carboxamides via the succinimide esters | |
| CN113444039B (en) | A kind of method utilizing ionic liquid to prepare 2,2,4-trimethyl-1,2-dihydroquinoline | |
| CN116283635A (en) | A method for synthesizing N,3,3-trimethyl-2-oxobutanamide | |
| CN107674062B (en) | Anti-hepatitis C drug intermediate, preparation method and application | |
| CN107011185A (en) | One group is used for isotope labeling reagent and its synthetic method that carboxyl is marked | |
| CN103864705B (en) | Polypeptide condensating agent 1-hydroxy-1,2,3-phentriazine-4(3H)-one and preparation method thereof | |
| CN101880262A (en) | The preparation method of 2-thiazolidinone | |
| CN104130195A (en) | Synthetic method for carbendazim hapten | |
| CN114213283B (en) | Method for preparing [2-[1-(Fmoc-amino)ethoxy]ethoxy]acetic acid in one pot | |
| CN104910068B (en) | A kind of synthetic method of the tosilate of 2 cyano group isonicotinic acid hydrazide 1.5 | |
| CN105153023B (en) | The synthetic method of 2 amino, 4 bromopyridine | |
| CN111116421B (en) | Preparation method of amide derivative | |
| CN111848546B (en) | A kind of 2-(aminomethyl)thiazole-5-carbonitrile and its synthetic method | |
| CN106543050A (en) | Synthetic process of apremilast intermediate | |
| CN107573263B (en) | Synthetic method of omega-substituted biuret compound | |
| CN115181139B (en) | Method for synthesizing On-DNA (deoxyribonucleic acid) dihydroquinazolinone compound by using aminobenzonitrile compound | |
| CN110981750A (en) | Method for synthesizing 2-pentanone oxime from 2-pentanone through ammoxidation | |
| CN105198825B (en) | A kind of preparation method of D seromycins | |
| CN107602317A (en) | The preparation method of the chiral Arvlacetic derivatives of 2 amino 2 | |
| CN108409590B (en) | A kind of betaine hydrochloride hydroxylamine and its preparation method and application | |
| WO2018176253A1 (en) | Group of isotope labelling reagents for carboxyl labelling and synthesis method therefor | |
| CN112175021B (en) | Method for synthesizing On-DNA aryl benzyl substituted compound | |
| JP2565034B2 (en) | Novel dopa derivative and its production method | |
| CN115197084A (en) | Preparation method of enzalutamide key intermediate |
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 |