FIELD: pharmacology.
SUBSTANCE: invention relates to a novel method for preparing a pyrazole-carboxylic acid derivative of the formula (I) wherein R1 is C1-7-alkyl and R3 is C1-7-alkyl which is optionally substituted by halogen or C1-4-alkoxy. The pyrazole-carboxylic acid derivative of the formula I can be used as a structural element in the preparation of pharmaceutically active components, for example compounds performing the function of phosphodiesterase (PDE) inhibitors, especially PDE10 inhibitors. PDE10 inhibitors have the ability to treat psychotic disorders similar to schizophrenia. The proposed method comprises the following stages: a) reacting the oxoacetate of formula II, where R2 is C1-7-alkyl and X is halogen, with an acrylate of formula III, where R1 is as described above, and R4 and R5 are C1-7-alkyl, in the presence of a base with formation of an ester of aminomethylene-succinic acid of formula IV, where R1, R2, R4 and R5 are as described above; B) coupling an ester of aminomethylene-succinic acid of formula IV with an N-protected hydrazine derivative of formula V, where R3 is as described above, and R6 is an amino-protecting group, with formation of a hydrazinomethylene-succinic acid ester of the formula VI, where R1, R2, R3 and R6 are as described above; C) closing the ring of the hydrazinomethylene-succinic acid ester of the formula VI under acidic conditions with formation of the pyrazole-dicarboxylic acid ester of the formula VII, where R1, R2 and R3 are as described above, and d) hydrolyzing the pyrazole-dicarboxylic acid ester of the formula VII in the 3-position with a base with formation of the pyrazole-carboxylic acid derivative of the formula I. The invention also relates to an intermediate ester of the hydrazinomethylene-succinic acid of the formula VI.
EFFECT: increased selectivity of the process, which will allow to obtain the target compound on an industrial scale.
16 cl, 5 ex
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