- 2-amino-5-heteroaryl substituted pyrazine derivative and application thereof
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The invention provides a 2-amino-5-heteroaryl substituted pyrazine derivative with a chemical structure as shown in a formula 1, a pharmaceutical preparation containing the 2-amino-5-heteroaryl substituted pyrazine derivative, and application of the 2-amino-5-heteroaryl substituted pyrazine derivative in drugs for treating or preventing malaria. Compared with the prior art, the compound has the effects of resisting plasmodium falciparum proliferation and resisting plasmodium falciparum of different strains, and has the advantages of longer half-life period, lower plasma clearance rate, higher distribution volume and better oral bioavailability.
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Paragraph 0077-0078; 0080
(2021/05/29)
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- A General C(sp3)-C(sp3) Cross-Coupling of Benzyl Sulfonylhydrazones with Alkyl Boronic Acids
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A general transition-metal-free cross-coupling between benzylic sulfonylhydrazones and 1°, 2°, or 3° alkyl boronic acids is reported. The base-promoted reaction is operationally simple and exhibits a broad substrate scope to forge a variety of alkyl-alkyl bonds, including between sterically encumbered secondary and tertiary sp3-carbons. The ability of this method to simplify retrosynthetic analysis is exemplified by the improved synthesis of multiple medicinally relevant scaffolds.
- Merchant, Rohan R.,Lopez, Jovan A.
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supporting information
p. 2271 - 2275
(2020/03/13)
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- Synthesis method of cyclopropyl boric acid
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The invention discloses a synthesis method of cyclopropyl boric acid, and belongs to the field of boric acid synthesis in organic chemistry. The synthesis method comprises the following steps: starting from formyl boric acid, enabling the formyl boric acid with strong electron-withdrawing sulfohydrazide to generate hydrazone, then introducing ethylene under the catalysis of ferriporphyrin, and reacting, thus obtaining the cyclopropyl boric acid. The synthesis method disclosed by the invention is simple in operation, the use of cyclopropyl bromide in a traditional technological method is avoided by adopting cyclopropanation reaction under metal catalysis, and a new synthesis path is provided for synthesis of the cyclopropyl boric acid.
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Paragraph 0016; 0017; 0018; 0019
(2019/02/19)
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- Method for preparing cyclopropylboronic acid on basis of carbene insertion process
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The invention discloses a method for preparing a cyclopropylboronic acid on the basis of a carbene insertion process and belongs to the technical field of organic synthesis. The method comprises the following steps: (1) acquiring cyclopropyl borate from the reaction of vinyl borate (or salt) and methylene carbene and (2) decomposing the cyclopropyl borate (salt) into the cyclopropylboronic acid. The method disclosed by the invention is mild in reaction conditions, easily acquired in raw materials, simple in operation, easy in purification and suitable for mass production. A new method for compounding the cyclopropylboronic acid is provided.
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Paragraph 0031; 0032; 0033-0039
(2019/01/08)
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- A process for the preparation method of the cyclopropyl-boronic acid
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The invention discloses a method for preparing cyclopropyl boronic acid. Cyclopropyl methanoic acid is adopted as a raw material and added into a solution obtained after n-butyllithium reacts with organic alkali at the low temperature, and then a boronizing reagent is added into the mixture; after boronation is finished, acid is added for quenching to obtain 1-carboxyl cyclopropyl boronic acid; the intermediate is added into high-boiling-point solvent and heated until the temperature is 80 DEG C-150 DEG C, after reaction deacidification, methylbenzene is added into the mixed solution for dehydration to form cyclopropyl boronic acid trimer, and the cyclopropyl boronic acid trimer is hydrolyzed to obtain the cyclopropyl boronic acid; the melting point of the obtained cyclopropyl boronic acid is 90 DEG C-95 DEG C, and the HNMR purity of the obtained cyclopropyl boronic acid is over 98%. The method is easy to operate and suitable for industrial scale-up production, and no highly toxic chemical is used in the whole process.
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Paragraph 0026; 0027; 0033; 0034; 0040; 0041
(2017/06/30)
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- Organotrifluoroborate hydrolysis: Boronic acid release mechanism and an acid-base paradox in cross-coupling
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The hydrolysis of potassium organotrifluoroborate (RBF3K) reagents to the corresponding boronic acids (RB(OH)2) has been studied in the context of their application in Suzuki-Miyaura coupling. The "slow release" strategy in such SM couplings is only viable if there is an appropriate gearing of the hydrolysis rate of the RBF3K reagent with the rate of catalytic turnover. In such cases, the boronic acid RB(OH)2 does not substantially accumulate, thereby minimizing side reactions such as oxidative homocoupling and protodeboronation. The study reveals that the hydrolysis rates (THF, H2O, Cs2CO 3, 55 °C) depend on a number of variables, resulting in complex solvolytic profiles with some RBF3K reagents. For example, those based on p-F-phenyl, naphthyl, furyl, and benzyl moieties are found to require acid catalysis for efficient hydrolysis. This acid-base paradox assures their slow hydrolysis under basic Suzuki-Miyaura coupling conditions. However, partial phase-splitting of the THF/H2O induced by the Cs2CO 3, resulting in a lower pH in the bulk medium, causes the reaction vessel shape, material, size, and stirring rate to have a profound impact on the hydrolysis profile. In contrast, reagents bearing, for example, isopropyl, β-styryl, and anisyl moieties undergo efficient "direct" hydrolysis, resulting in fast release of the boronic acid while reagents bearing, for example, alkynyl or nitrophenyl moieties, hydrolyze extremely slowly. Analysis of B-F bond lengths (DFT) in the intermediate difluoroborane, or the Swain-Lupton resonance parameter (R) of the R group in RBF3K, allows an a priori evaluation of whether an RBF3K reagent will likely engender "fast", "slow", or "very slow" hydrolysis. An exception to this correlation was found with vinyl-BF 3K, this reagent being sufficiently hydrophilic to partition substantially into the predominantly aqueous minor biphase, where it is rapidly hydrolyzed.
- Lennox, Alastair J. J.,Lloyd-Jones, Guy C.
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supporting information; experimental part
p. 7431 - 7441
(2012/06/16)
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- SLOW RELEASE OF ORGANOBORONIC ACIDS IN CROSS-COUPLING REACTIONS
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A method of performing a chemical reaction includes reacting a compound selected from the group consisting of an organohalide and an organo-pseudohalide, and a protected organoboronic acid represented by formula (I) in a reaction mixture: R1-B-T; where R1 represents an organic group, T represents a conformationalIy rigid protecting group, and B represents boron having sp3 hybridization. When unprotected, the corresponding organoboronic acid is unstable by the boronic acid neat stability test. The reaction mixture further includes a base having a pKB of at least 1 and a pal ladium catalyst. The method further includes forming a cross-coupled product in the reaction mixture.
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Page/Page column 41, 44
(2010/04/27)
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- COMBINATION THERAPY METHOD FOR TREATING HEPATITIS C VIRUS INFECTION AND PHARMACEUTICAL COMPOSITIONS FOR USE THEREIN
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Combination therapy methods for the treatment of hepatitis C virus infection and associated diseases, by the co-administration of 5-cyclopropyl-2- (4-fluoro-phenyl-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran- 3-carboxylic acid methylamide or a pharmaceutically acceptable salt thereof with natural, recombinant or modified interferon, that effectively inhibit viral replication.
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Page/Page column 15
(2008/06/13)
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- ARYL SULFONES AND USES RELATED THERETO
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Aryl sulfone compounds of formula (I) and (II) are described and have therapeutic utility, particularly in the treatment of diabetes, obesity and related conditions and disorders.
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Page/Page column 82
(2010/02/14)
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- Phenylenediamine urotensin-II receptor antagonists and CCR-9 antagonists
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The present invention relates to urotensin II receptor antagonists, CCR-9 antagonists, pharmaceutical compositions containing them and their use.
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- BENZOXAZOCINES AND THEIR USE AS MONOAMINE-REUPTAKE INHIBITORS
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Compounds of the general formula (1), wherein one of W, X, Y and Z is N or CR4 and the others are each CH; and R4 is a specified substituent. These compounds inhibit monoamine reuptake, and are useful in the treatment of pain, emesis depression, post traumatic stress disorders, attention deficit disorders, obsessive compulsive disorders, pre-menstrual syndrome, substance abuse and sexual dysfunction.
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- Cyclopropylboronic acid: Synthesis and Suzuki cross-coupling reactions
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An efficient synthesis of cyclopropylboronic acid is reported. This compound undergoes efficient Suzuki-type coupling reactions with a range of aryl and heteroarybromides.
- Wallace, Debra J.,Chen, Cheng-Yi
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p. 6987 - 6990
(2007/10/03)
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