- Development of Scalable Processes for the Preparation of N-Methyl-3-Bromo-5-Methyl Pyrazole
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The development and optimization of two scalable routes to N-methyl-3-bromo-5-methyl pyrazole is described. The initial Sandmeyer route entailed a three-step sequence from crotonitrile and methyl hydrazine, proceeding through the 3-amino pyrazole intermediate. Due to the GTI liability of the 3-amino pyrazole intermediate, a tedious steam-distillation, and 30% overall yield, we developed a second-generation Sandmeyer-free approach from methyl crotonate and methyl hydrazine which leveraged a condensation, bromination, and oxidation sequence. Process development led to the improved preparation of N-methyl-3-bromo-5-methyl pyrazole with increased efficiency and overall yield. The isolation, handling, and storage of the final product was greatly improved through the generation of the triflic acid salt, and salt form studies are also discussed.
- Fox, Richard J.,Markwalter, Chester E.,Lawler, Michael,Zhu, Keming,Albrecht, Jacob,Payack, Joseph,Eastgate, Martin D.
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p. 754 - 762
(2017/05/29)
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- SMALL MOLECULE INHIBITORS OF MCL-1 AND USES THEREOF
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This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having pyrazolopyridine structure which function as inhibitors of Mcl-1 protein, and their use as therapeutics for the treatment of cancer and other diseases.
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Paragraph 0141
(2015/10/28)
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- PYRAZOLE DERIVATIVES
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Disclosed are compounds of general formula (I), wherein R, R1, Rc, Rd, Re, Rf, X, Y, Z, A and B are as defined in the application.
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Paragraph 0137
(2013/04/23)
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- PYRAZOLE DERIVATIVES
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Disclosed are compounds of general formula (I), wherein R, R1, Rc, Rd, Re, Rf, X, Y, Z, A and B are as defined in the application.
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Paragraph 0253
(2013/06/26)
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- 2,4-DIAMINO-6,7-DIHYDRO-5H-PYRROLO[2,3]PYRIMIDINE DERIVATIVES AS FAK/Pyk2 INHIBITORS
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The invention relates to a novel class of 2,4-diamino-6,7-dihydro-5H-pyrrolo[2,3]pyrimidine derivatives as a FAK and/or Pyk2 inhibitor, to a process for their preparation, and to a composition thereof, as well as to use of the compounds for the inhibiting FAK and/or Pyk2 and method for the treatment of a FAK and/ or Pyk2 mediated disorder or disease.
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Page/Page column 59
(2012/07/27)
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- The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist
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The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A selective over PR is described. Associated structure-activity relationships and the process of optimisation of an initial HTS hit are also described.
- Rimland, Joseph,Dunne, Angela,Hunjan, Suchete S.,Sasse, Rosemary,Uings, Iain,Montanari, Dino,Caivano, Matilde,Shah, Poonam,Standing, David,Gray, David,Brown, David,Cairns, William,Trump, Ryan,Smith, Paul W.,Bertheleme, Nicolas,D'Alessandro, Pier,Gul, Sheraz,Vimal, Mythily,Smith, David N.,Watson, Stephen P.
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scheme or table
p. 2340 - 2343
(2010/08/22)
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- Approach to the library of fused pyridine-4-carboxylic acids by combes-type reaction of acyl pyruvates and electron-rich amino heterocycles
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A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.
- Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Plaskon, Andrey S.,Dmytriv, Yuri V.,Grygorenko, Oleksandr O.,Mykhailiuk, Pavel K.,Krotko, Dmitriy G.,Pushechnikov, Alexei,Tolmachev, Andrey A.
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scheme or table
p. 510 - 517
(2010/09/05)
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- Condensation of 1-substituted 5-aminopyrazoles with β-dicarbonyl compounds
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Condensation of N-substituted 5-aminopyrazoles with β-diketones occurs with the formation of pyrazolo[4,5-b]pyridines. Depending on the conditions, their reaction with β-keto acids can give either 6-oxo- or 4-oxopyrazolo[4,5-b]pyridines.
- Nam,Grandberg,Sorokin
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p. 937 - 942
(2007/10/03)
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- Composition for dyeing keratin fibers which contain at least one diaminopyrazole, dyeing process, novel diaminopyrazoles and process for their preparation
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The invention relates to novel compositions for the oxidation dyeing of keratin fibers, comprising at least one specific diaminopyrazole derivative, to the dyeing process using this composition, to novel diaminopyrazole derivatives and to a process for their preparation.
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Page column 15
(2008/06/13)
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- Composition for dyeing keratin fibers which contain at least one diaminopyrazole, dyeing process, novel diaminopyrazoles and process for their preparation
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The invention relates to novel compositions for the oxidation dyeing of keratin fibers, comprising at least one specific diaminopyrazole derivative, to the dyeing process using this composition, to novel diaminopyrazole derivatives and to a process for their preparation.
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- Synthesis of N(1)-substituted 5-amino-3-methylpyrazoles
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With the aim of preparing new biologically active compounds a series of N(1)-substituted 5-amino-3-methylpyrazoles has been obtained from β-aminocrotononitrile and mono-substituted hydrazines.
- Nam,Grandberg,Sorokin
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p. 281 - 283
(2007/10/03)
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- Pyrazolopyridine analogs of mevalonolactone and derivatives thereof useful for inhibiting cholesterol biosynthesis in mammals
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Compounds of the formula STR1 and processes for and intermediates in the synthesis thereof, pharmaceutical compositions comprising such a compound and the use of such compounds for inhibiting cholesterol biosynthesis and lowering the blood cholesterol level and, therefore, in the treatment of hyperlipoproteinemia and atherosclerosis.
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