41653-96-7Relevant articles and documents
A new synthetic route for the preparation of pregabalin
He, Chasheng,Zhai, Ziran,Zhou, Yang,Li, Jianqi,Wang, Guan
supporting information, p. 2034 - 2040 (2021/05/31)
We reported the synthesis of (S)-pregabalin in a five-step sequence with 20% overall yield. As a modification of the previously developed route, a Michael addition between CH3NO2 and chiral oxaoxazolidinone was employed as a key operation for introducing the methyleneamino group, which allowed avoiding the use of toxic cyanide reagent and led to enantiomerically pure product (>99% ee) after the recrystallization in appropriate solvent.
Ligand-controlled divergent dehydrogenative reactions of carboxylic acids via C–H activation
Wang, Zhen,Hu, Liang,Chekshin, Nikita,Zhuang, Zhe,Qian, Shaoqun,Qiao, Jennifer X.,Yu, Jin-Quan
, p. 1281 - 1285 (2021/12/10)
Dehydrogenative transformations of alkyl chains to alkenes through methylene carbon-hydrogen (C–H) activation remain a substantial challenge. We report two classes of pyridine-pyridone ligands that enable divergent dehydrogenation reactions through palladium-catalyzed b-methylene C–H activation of carboxylic acids, leading to the direct syntheses of a,b-unsaturated carboxylic acids or g-alkylidene butenolides. The directed nature of this pair of reactions allows chemoselective dehydrogenation of carboxylic acids in the presence of other enolizable functionalities such as ketones, providing chemoselectivity that is not possible by means of existing carbonyl desaturation protocols. Product inhibition is overcome through ligand-promoted preferential activation of C(sp3)–H bonds rather than C(sp2)–H bonds or a sequence of dehydrogenation and vinyl C–H alkynylation. The dehydrogenation reaction is compatible with molecular oxygen as the terminal oxidant.
Synthesis method of pregabalin intermediate 3-nitromethylene-5-methyl-ethyl hexanoate
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Paragraph 0022; 0023-0025, (2020/02/27)
The invention provides a synthesis method of a pregabalin intermediate, namely 3-nitromethylene-5-methyl-ethyl hexanoate. The synthesis method comprises the following steps: (1) reacting isovaleraldehyde with malonic acid in a choline chloride-urea eutectic solvent to obtain 5-methyl-2-hexenoic acid; (2) reacting the 5-methyl-2-hexenoic acid with absolute ethyl alcohol in a choline chloride-methanesulfonic acid eutectic solvent to obtain 5-methyl-2- ethyl hexanoate; and (3) reacting the 5-methyl-2- ethyl hexanoate with nitromethane in a choline chloride-urea eutectic solvent to obtain the 3-nitromethylene-5-methyl- ethyl hexanoate. The method does not need an organic solvent, is green, low in toxicity, environment-friendly, simple to operate, simple in post-treatment, high in yield and lowin cost, and is a green and efficient synthesis method for synthesizing the pregabalin intermediate.
Method for preparing 5-methyl-2-hexenoic acid
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Paragraph 0021-0041, (2019/09/13)
The invention discloses a method for preparing 5-methyl-2-hexenoic acid. The method is characterized in that isovaleraldehyde and malonic acid undergo a Knoevenagel condensation reaction and a decarboxylation reaction with KF/K2CO3/gamma-Al2O3 as a catalyst in order to obtain the 5-methyl-2-hexenoic acid. The 5-methyl-2-hexenoic acid product produced through the method by using the isovaleraldehyde and malonic acid as raw materials and the KF/K2CO3/gamma-Al2O3 compound as the catalyst has a yield of 93% or above and a purity of 99.7% or above; the KF/K2CO3/gamma-Al2O3 compound is inexpensive,has no toxic or side effects, and can be recycled, so the input cost of the catalyst is reduced; and the method has the advantages of simple synthesis route, good reproducibility, and easiness in industrial production enforcement of the 5-methyl-2-hexenoic acid.
Phosphodiesterase inhibitor, and applications thereof
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Paragraph 0094; 0098-0100, (2018/09/08)
The invention belongs to the technical field of medicine, and more specifically relates to a phosphodiesterase 9 (PDE9) inhibitor represented by formula I, and pharmaceutically acceptable salts, solvates, polymorphic substances, and isomers thereof, and also relates to medicinal preparations, and pharmaceutical compositions of the above compounds, and applications of the medicinal preparations andpharmaceutical compositions. The compounds and the pharmaceutically acceptable salts, solvates, polymorphic substances, and isomers can be used in treatment of phosphodiesterase 9 (PDE9) abnormal expression mediated related diseases.
Mechanistic Studies of the Deslongchamps Annulation
Kreibich, Michael,Petrovi?, Denis,Brückner, Reinhard
supporting information, p. 1116 - 1133 (2018/02/14)
The Cs2CO3-mediated annulations ("Deslongchamps annulations") of three spirocyclic benzoquinone monoketals 5b-d with an ester or acyl substituent at C-2 to two tert-butyl esters of λδ-unsaturated β-ketocarboxyl acids ("Nazarov reagents" 2a,b) were monitored 1H NMR spectroscopically. This revealed that a primary product, by all likelihood the Michael adduct, forms fast and prior to the appearance of the Deslongchamps adduct. These primary products form reversibly. This was proved by two crossover and four scavenging experiments. Therein, components already incorporat.
Enantioselective Synthesis of N?H-Free 1,5-Benzothiazepines
Wang, Guojin,Tang, Yu,Zhang, Yu,Liu, Xiaohua,Lin, Lili,Feng, Xiaoming
supporting information, p. 554 - 557 (2017/01/18)
An enantioselective sulfa-Michael-cyclization reaction was developed for the synthesis of 1,5-benzothiazepines with versatile pharmacological activities. The reaction between 2-aminothiophenol and α,β-unsaturated pyrazoleamides gave direct access to N?H-free 1,5-benzothiazepines in the presence of a chiral N,N′-dioxide/Yb(OTf)3complex. Excellent enantioselectivities (up to 96 % ee) and high yields (up to 99 %) were obtained for a broad range of substrates under mild reaction conditions. This method provided a facile approach to the antidepressant drug (R)-(?)-Thiazesim.
Screening and Engineering the Synthetic Potential of Carboxylating Reductases from Central Metabolism and Polyketide Biosynthesis
Peter, Dominik M.,Schada Von Borzyskowski, Lennart,Kiefer, Patrick,Christen, Philipp,Vorholt, Julia A.,Erb, Tobias J.
supporting information, p. 13457 - 13461 (2015/11/09)
Carboxylating enoyl-thioester reductases (ECRs) are a recently discovered class of enzymes. They catalyze the highly efficient addition of CO2 to the double bond of α,β-unsaturated CoA-thioesters and serve two biological functions. In primary metabolism of many bacteria they produce ethylmalonyl-CoA during assimilation of the central metabolite acetyl-CoA. In secondary metabolism they provide distinct α-carboxyl-acyl-thioesters to vary the backbone of numerous polyketide natural products. Different ECRs were systematically assessed with a diverse library of potential substrates. We identified three active site residues that distinguish ECRs restricted to C4 and C5-enoyl-CoAs from highly promiscuous ECRs and successfully engineered a selected ECR as proof-of-principle. This study defines the molecular basis of ECR reactivity, allowing for predicting and manipulating a key reaction in natural product diversification.
Diasteroselective conjugate addition of diethylaluminum cyanide to a conjugated N -enoyl system: An alternative synthesis of (S)-pregabalin
Tovar-Gudino, Erika,Morales-Nava, Rosmarbel,Fernandez-Zertuche, Mario
, p. 45 - 48 (2014/02/14)
We have explored in this work the conjugate addition of diethylaluminum cyanide (Nagata's reagent) to an N-enoyl system bearing the (R)-4-phenyl-2- oxazolidinone chiral auxiliary. Since this method provided a practical synthesis of γ-amino acids, we report the conjugate addition of diethylaluminum cyanide as the key step in the synthesis of (S)-pregabalin 1 in a five-step sequence of reactions from commercially available starting materials.
A protocol for accessing the β-azidation of α,β-unsaturated carboxylic acids
Angelini, Tommaso,Bonollo, Simona,Lanari, Daniela,Pizzo, Ferdinando,Vaccaro, Luigi
, p. 4610 - 4613 (2012/10/30)
This contribution reports the preparation and use of a new immobilized catalyst, PS-DABCOF (9), which has been specifically designed to access for the first time the efficient β-azidation of α,β-unsaturated carboxylic acids.
