Process for the preparation of pyrazole carboxylic acid derivatives
AssigneeHoffman-La Roche Inc.
InventorsBjoern Bartels, Fritz Bliss, Katrin Groebke Zbinden, Matthias Koerner
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Abstract
The present invention relates to a novel process for the preparation of a pyrazole carboxylic acid derivative of the formula wherein R1 is C1-7-alkyl and R3 is C1-7-alkyl which is optionally substituted with halogen or C1-4-alkoxy. The pyrazole carboxylic acid derivative of the formula I can be used as building block in the preparation of pharmaceutically active principles e.g. for compounds acting as phosphodiesterase (PDE) inhibitors, particularly PDE10 inhibitors. PDE10 inhibitors have the potential to treat psychotic disorders like schizophrenia.
Claims16
Process for the preparation of a pyrazole carboxylic acid derivative of the formula
- wherein R1 is C1-7-alkyl and R3 is C1-7-alkyl which is optionally substituted with halogen or C1-4-alkoxy comprising the steps,
- a) reacting an oxoacetate of the formula
- wherein R2 is C1-7-alkyl and X is halogen with an acrylate of the formula
- wherein R1 is as above and R4 and R5 are C1-7-alkyl in the presence of a base to form an aminomethylene succinic acid ester of the formula
- wherein R1, R2, R4 and R5 are as above;
- b) coupling the aminomethylene succinic acid ester of the formula IV with an N-protected hydrazine derivative of formula
- wherein R3 is as above and R6 is an amino protecting group to form the hydrazinomethylene succinic acid ester of the formula
- wherein R1, R2, R3 and R6 are as above;
- c) ring closing the hydrazinomethylene succinic acid ester of formula VI under acidic conditions to form the pyrazole dicarboxylic acid ester of the formula
- wherein R1, R2 and R3 are as above and;
- d) hydrolyzing the pyrazole dicarboxylic acid ester of the formula VII in 3-position with a base to form the pyrazole carboxylic acid derivative of the formula I.
Hydrazinomethylene succinic acid ester of the formula
- wherein R1 and R2 are C1-7-alkyl and R3 is C1-7-alkyl which is optionally substituted with halogen or C1-4-alkoxy and R6 stands for an amino protecting group.
Dependencies are inferred from the claim text.