1006376-61-9Relevant articles and documents
Comparison of a Batch and Flow Approach for the Lipase-Catalyzed Resolution of a Cyclopropanecarboxylate Ester, A Key Building Block for the Synthesis of Ticagrelor
Hugentobler, Katharina G.,Rasparini, Marcello,Thompson, Lisa A.,Jolley, Katherine E.,Blacker, A. John,Turner, Nicholas J.
, p. 195 - 199 (2017)
In this study a batch reactor process is compared to a flow chemistry approach for lipase-catalyzed resolution of the cyclopropanecarboxylate ester (±)-3. (1R,2R)-3 is a precursor of the amine (1R,2S)-2 which is a key building block of the API ticagrelor. For both flow and batch operation, the biocatalyst could be recycled several times, whereas in the case of the flow process the reaction time was significantly reduced.
Controllable stereoinversion in DNA-catalyzed olefin cyclopropanationviacofactor modification
Cheng, Yu,Hao, Jingya,Jia, Guoqing,Li, Can,Lu, Shengmei,Miao, Wenhui
, p. 7918 - 7923 (2021/06/16)
The assembly of DNA with metal-complex cofactors can form promising biocatalysts for asymmetric reactions, although catalytic performance is typically limited by low enantioselectivities and stereo-control remains a challenge. Here, we engineer G-quadruplex-based DNA biocatalysts for an asymmetric cyclopropanation reaction, achieving enantiomeric excess (eetrans) values of up to +91% with controllable stereoinversion, where the enantioselectivity switches to ?72% eetransthrough modification of the Fe-porphyrin cofactor. Complementary circular dichroism, nuclear magnetic resonance, and fluorescence titration experiments show that the porphyrin ligand of the cofactor participates in the regulation of the catalytic enantioselectivityviaa synergetic effect with DNA residues at the active site. These findings underline the important role of cofactor modification in DNA catalysis and thus pave the way for the rational engineering of DNA-based biocatalysts.
Preparation method of phenyl-containing compound
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, (2022/01/04)
The present invention discloses a method for preparing an phenyl-containing compound. The present invention provides a method for preparing a compound shown in formula I, comprising the following steps: in the presence of formamide or acetamide, in the pr
Preparation method of chiral aromatic cyclopropylamine and salt thereof and intermediate used in preparation method
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Paragraph 0076-0078, (2020/06/20)
The embodiment of the invention provides a preparation method of a compound as shown in a formula I or salt thereof, which comprises the following steps: (1) reacting a compound as shown in a formulaVI with a compound as shown in a formula VII in a first
Preparation method of ticagrelor
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Paragraph 0035; 0040; 0044; 0084; 0125, (2018/04/21)
The invention discloses a preparation method of ticagrelor. The preparation method comprises the following steps: (1) preparation of ticagrelor intermediate product 1-TK acid; (2) preparation of ticagrelor intermediate product 2-TK-amide; (3) preparation of ticagrelor intermediate product 3-TK-amino compound hydrochloride; (4) preparation of ticagrelor intermediate product 4-TK-amino compound R-tartrate; ( 5) preparation of ticagrelor intermediate product 5-TK-amino compound L-mandelate; and (6) preparation of ticagrelor-TK. The preparation method has the advantages of cost advantage, mature and stable process, stable product quality, and safe and reliable production process.
Method for preparing ticagrelor intermediate
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, (2018/03/06)
The invention discloses a method for preparing a ticagrelor intermediate. The method comprises the following steps: taking o-difluorobenzene and chloroacetyl chloride as initial raw materials, carrying out an F-K reaction, a bio-enzyme fermentation technology asymmetric reduction reaction, a ring-closure reaction and a cyclopropanation reaction, so as to obtain the key intermediate (1R, 2R)-2-(3,4-difluorophenyl) cyanocyclopropane carboxylate of the ticagrelor at high yield, high enantioselectivity and high purity. The method can realize industrialized production. The method is low in energy consumption, less in pollution, green, clean, high in yield and high in purity, the cost is reduced, the product quality is stable, and the method is suitable for large-scale stable industrial production.
Development of a Practical Enzymatic Process for Preparation of (S)-2-Chloro-1-(3,4-difluorophenyl)ethanol
Guo, Xiang,Tang, Jia-Wei,Yang, Jiang-Tao,Ni, Guo-Wei,Zhang, Fu-Li,Chen, Shao-Xin
, p. 1595 - 1601 (2017/10/25)
(S)-2-Chloro-1-(3,4-difluorophenyl)ethanol (1) is a vital chiral intermediate for the synthesis of Ticagrelor - an effective treatment for acute coronary syndromes. A ketoreductase (KRED) KR-01 in our KRED library was screened to transform 2-chloro-1-(3,4
(1 R, 2 S) - 2 - (3, 4 - difluorophenyl) amine ·D - mandelic acid salt preparation method
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Paragraph 0115-0118, (2018/02/04)
The invention discloses a preparation method of (1R,2S)-2-(3,4-difluorophenyl) rolicyprine.D-mandelate. The preparation method comprises the following steps: carrying out cyclopropanation on a compound shown in a formula V to obtain a compound shown in a formula IV; carrying out amide generation and Hofmann degradation to obtain a compound shown in a formula II; and performing salification with D-mandelic acid to obtain a compound shown in a formula I. The compound shown in the formula V is prepared in a way that a compound shown in a structure formula VI is subjected to CBS asymmetric reduction reaction, wherein a catalyst for the CBS asymmetric reduction reaction is a compound shown in a structural formula VII, and a reduction agent for the CBS asymmetric reduction reaction can be borane-tetrahydrofuran or borane-N,N-diethyl phenylamine.
HEMOPROTEIN CATALYSTS FOR IMPROVED ENANTIOSELECTIVE ENZYMATIC SYNTHESIS OF TICAGRELOR
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Paragraph 0211; 0212; 0221; 0222, (2016/12/22)
The present invention provides methods by which trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine and related cyclopropane compounds are prepared using synthetic strategies that include a biocatalytic cyclopropanation step.
