DE1946370

1307005 Derivatives of pyrazole-4-acetic acid BYK GULDEN LOMBERG CHEMISCHE FABRIK GmbH 9 Sept 1970 [12 Sept 1969] 43147/70 Heading C2C The invention comprises compounds of formula and their salts with pharmacologically compatible bases, wherein R1, R2, R3 are each H, an (up to C 7 ) aliphatic or cycloaliphatic hydrocarbon radical, or an (up to C 12 ) optionally substituted (otherwise than by NO 2 ) aryl or heteroaryl group, or R1 is benzyl (optionally halogen- or C 1-4 alkoxy-substituted), provided that when R 2 is H, R 3 may not be H or Me; R4 is H, C 1-3 alkyl or C 3-6 cycloalkyl; and A is,CO 2 H, CO 2 R5, CONR6R7, CN or C(:NOH)OH, where R5 is C 1-4 alkyl, benzyl, Ph or 2-HO 2 CC 6 H 4 , and R6, R7 are each H or C 1-4 alkyl, or NR6R7 is pyrrolidino, piperidino or morpholino. The following preparative methods are exemplified: (1) reacting R2CMe NNHR1 with reaction product and hydrolysing the compound thus formed (or alternatively first forming from the initial product the N,N.dimethyl-4-pyrazolyl. methyleneiminium perchlorate, and hydrolysing this) to give the corresponding 4-formylpyrazole, reducing the latter to the 4-hydroxymethylpyrazole, converting this via the 4-chloromethylpyrazole to the 4-cyanomethyl compound and optionally hydrolysing this to the acid; (2) reacting the diketo ester with R1NHNH 2 ; (3) reacting an alkyl-3-acyl-4- dialkylamino - 3 - butenoate with R1NHNH 2 ; (4) interconversion of acids, esters, nitriles, and amides, by known methods; (5) reacting the corresponding acid chloride with HNR6R7 or with NH 2 OH; (6) reacting a compound where R1 =Na, with R1-halide (R1#H), (7:) hydrolysing (e.g.) 3,5 - dimethyl - 1 - phenyl - 4 - pyrazolethioacetmorpholide to the corresponding acid; (8) hydrolysing (e.g.) ethyl 3,5-dimethyl-1- phenyl - 4 - pyrazoleacetimidate to the corresponding acetate. Therapeutic compositions for oral, parenteral or rectal administration comprise compounds of the above formula, which have antiphlogistic, analgesic and antipyretic properties.