US 12,221,420 B2
Process for the preparation of substituted pyrazole derivatives
Paul Spurr, Riehen (CH); and Rene Trussardi
Assigned to Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed by Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed on Jan. 7, 2022, as Appl. No. 17/571,182.
Application 17/571,182 is a continuation of application No. PCT/EP2020/069317, filed on Jul. 9, 2020.
Claims priority of application No. 19185640 (EP), filed on Jul. 11, 2019; and application No. 19194896 (EP), filed on Sep. 2, 2019.
Prior Publication US 2022/0127236 A1, Apr. 28, 2022
Int. Cl. C07D 231/14 (2006.01)
CPC C07D 231/14 (2013.01) 20 Claims
 
1. A method for preparing 5-ethyl-4-methyl-1H-pyrazole-3-carboxylic acid (1)

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without isolation of intermediates,
said method comprising:
a) reacting in the presence of a base pentan-3-one (4),

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 with a dialkyl or diaryl oxalate 5,

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wherein R is C1-C6-alkyl or C6-C14-aryl;
b) adding (i) a hydrazine hydrate in the presence of an acid, or (ii) a hydrazine salt to the reaction mixture obtained from step a);
c) adding an aqueous solution of an alkali metal hydroxide to the mixture obtained from step b); and
d) adjusting the pH of the mixture obtained from step c) to below pH 6 by adding an acid.