- Preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester
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The invention discloses a preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: with 1,3-dimethylpyrazole as a raw material, carrying out halogenation to obtain 4-halogenated-1,3,5-tetrahydronaphthalene; carrying out a reaction under the conditions of a bromination reagent and AIBN and hydrolysis with hexamethylenetetramine to obtain 4-halogen-1-methyl-1H-pyrazole-3-formaldehyde, then performing a reaction with a fluorination reagent to obtain 4-halogen-3-difluoromethyl-1-methylpyrazole; finally carrying out a reaction on the 4-halogen-3-difluoromethyl-1-methylpyrazole and a Grignard reagent to obtain 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester. The method is simple and convenient to operate and high in reaction yield, the purity of the obtained product can reach 99.5% or above, and the method has a potential process amplification prospect.
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- Preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid
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The invention discloses a preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, and belongs to the technical field of organic synthesis. The preparation method comprises thefollowing steps: reacting N-methyl-3-aminopyrazole as a raw material with bromine/iodine to replace pyrazole at site 4, then carrying out diazotizing and coupling with potassium difluoromethyl trifluoroborate to obtain 4-bromo-3-(difluoromethyl)-1-methyl-1H-pyrazole, then performing Grignard exchange by adopting isopropyl magnesium chloride and the like, and performing reaction with carbon dioxide to obtain 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. The method is simple and convenient to operate, the total yield of the three steps is as high as 64%, the product purity can reach 99.5% or above, the situation in which isomers exist in a traditional process is avoided, and the method has potential process amplification prospects.
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Paragraph 0030; 0033-0034; 0037; 0040-0041
(2020/07/15)
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- MACROCYCLIC AZOLOPYRIDINE DERIVATIVES AS EED AND PRC2 MODULATORS
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The invention relates to modulators of Embryonic Ectoderm Development (EED) and/or Polycomb Repressive Complex 2 (PRC2) useful in the treatment of disorders and diseases associated with EEC and PRC2, being macrocyclic azolopyridine derivatives and compositions thereof of Formula (I), or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, enantiomer, isomer, or tautomer thereof, wherein X1, X2, X3, A1, A2, Y, R1, R2, R3, and R4 are as described herein.
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Paragraph 0881
(2020/10/09)
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- Direct Regioselective [3 + 2] Cycloaddition Reactions of Masked Difluorodiazoethane with Electron-Deficient Alkynes and Alkenes: Synthesis of Difluoromethyl-Substituted Pyrazoles
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Phenylsulfone difluorodiazoethane (PhSO2CF2CHN2), an easy-to-prepare and bench-stable masked CF2-building block, has been developed. The synthetic utility of this reagent is demonstrated by a direct regioselecti
- Zeng, Jun-Liang,Chen, Zhen,Zhang, Fa-Guang,Ma, Jun-An
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p. 4562 - 4565
(2018/08/07)
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- TRIAZOLOPYRIMIDINE COMPOUNDS AND USES THEREOF
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A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein R1, R2, R3, R4, R5, and n are as defined herein.
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Paragraph 0368; 0369; 0378; 0379
(2016/07/27)
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- Method for the Production of N-Substituted (3-Dihalomethyl-1-Methyl-Pyrazole-4-yl) Carboxamides
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The present invention relates to a process for preparing N-substituted (3-dihalomethylpyrazol-4-yl)carboxamides of the formula (I) in which R1 is optionally substituted phenyl or C3-C7-cycloalkyl, R1a is hydrogen or fluorine, or R1a together with R1 is optionally substituted C3-C5-alkanediyl or C5-C7-cycloalkanediyl, R2 is C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl or C1-C4-alkoxy-C1-C2-alkyl, X is F or Cl and n is 0, 1, 2 or 3; which comprises A) providing a compound of the formula (II) in which X is F or Cl, Y is Cl or Br and R2 has one of the meanings given above and B) reacting a compound of the formula (II) with carbon monoxide and a compound of the formula (III) in which R1, R1a and n have one of the meanings given above; in the presence of a palladium catalyst; to intermediates used for the preparation according to the process according to the invention, and also to processes for their preparation.
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Page/Page column 17
(2010/07/10)
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- Process for the production of pyrazoles
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The present invention relates to novel processes for the production of compounds of formula I
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Page/Page column 9; 12-13
(2009/01/24)
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