3-(Piperidinyl)- and 3-(pyrrolidinyl)-1H-indazoles, a process for their preparation and their use as a medicament

Claim 1

1 . A process for the preparation of a compound of the formula wherein R is hydrogen, loweralkyl, loweralkenyl, lowercycloalkylloweralkyl, cyano, cyanomethyl, formyl, loweralkanoyl, or a group of the formulae R 1 is hydrogen, loweralkyl, loweralkenyl, lowercycloalkylloweralkyl, diloweralkylaminoloweralkyl, cyano, cyanomethyl, formyl, loweralkanoyl, hydroxymethyl, lowercycloalkylloweralkanoyl, or a group of the formulae or R 5 CO, 2- or 4-pyridinyl or 2-pyrimidinyl; R 2 and R 2 ' are independently loweralkyl, 2,2,2-trichloroethyl or phenyl, R 3 and R 4 are independently hydrogen or loweralkyl; R 5 represents the group furyl, thienyl, pyridinyl, thiazolyl, isothiazolyl, oxazolyl or isoxazolyl,. X, X' and X'' are independently hydrogen, halogen, loweralkyl, loweralkoxy, hydroxy, nitro, amino or trifluoromethyl; m is 2 or 3; n is 1 or 2; and the sum of m and n is 3 or 4; n' and n'' are independently 2 or 3; p, p' and p'' are independently 1 or 2; q and q' are independently 1, 2, 3 or 4; the optical antipode thereof, or the pharmaceutically acceptable acid addition salt thereof, which comprises cyclizing a compound of the formula wherein R, X, m, n and p are as above with hydrazine or hydrazine hydrate, to yield a compound of the formula 1 wherein R 1 is hydrogen and R, X, m, n and p are as defined above optionally treating a compound of the formula 1 wherein R 1 is hydrogen and R is as defined above with the proviso that R is not hydrogen, with an alkyl halide, alkenyl halide, cycloalkylalkyl halide, alkenyl halide, cycloalkylalkyl halide, dialkylaminoalkyl halide, cyanogen halide, cyanomethyl halide, 2- or 4-pyridyl halide, 2-pyrimidinyl halide, a compound of the formulae wherein X'', n'', q' and p" are as defined above and Hal is iodo, bromo or chloro in the presence of an alkali metal hydride to yield a compound of the formula 1 wherein R 1 is loweralkyl, loweralkenyl, lowercycloalkylloweralkyl, diloweralkylaminoloweralkyl, cyano, cyanomethyl or a group of the formulae 2- or 4-piperidinyl or 2-pyrimidinyl, and X, m, n and p are as defined above, or optionally reacting a compound of the formula 1 wherein R 1 is hydrogen and R is as defined above with the proviso that R is not hydrogen, and X, m, n and p are as defined above, with a formyl-, alkanoyl- or cycloalkylalkanoyl chloride, bromide or iodide or a compound of the formula R 2' OCO Hal or R 5 CO Hal, where R 2' , R 5 , X'', p'' and q are as defined above and Hal is chloro, bromo or iodo, or the corresponding acid anhydrides to yield a compound of the formula 1 wherein R 1 is formyl, lower alkanoyl, lowercycloalkylloweralkanoyl or a group of the formulae R 2' OCO or R 5 CO, or optionally reacting a compound of the formula 1 wherein R 1 is hydrogen and R is as defined above with the proviso that R is not hydrogen, with formaldehyd to yield a compound of the formula 1 wherein R 1 is h y-droxymethyl or reacting a compound of the formula 1 wherein R 1 is hydrogen and R is phenoxycarbonyl with formaldehyde and then removing the carbamoyl group by hydrolysis to yield a compound of the formula 1 wherein R 1 is hydroxymethyl and R is hydrogen, or optionally reacting a compound of the formula 1 wherein R 1 is hydrogen and R is as defined above but is not hydrogen, with a benzenesulfonyl halide of the formula wherein X" and p" are defined above and Hal is chlorine or bromine, to yield a compound of the formula 1 wherein R 1 is the group or optionally converting a compound of the formula 1 wherein R 1 is a group of the formulae wherein X" is the nitro group, by reduction of the nitro group to an amino function, diazotization and subsequent displacement or reduction of the diazonium moiety to a compound of the formula 1 whereim R 1 is a group of the formula where X" is hydrogen, halogen, alkyl, alkoxy, hydroxy or amino and p'' is 1 or 2, optionally reacting a compound of the formula 1 wherein R and R 1 are both hydrogen with a lower alkanoyl chloride, bromide or iodide or with a halide of the formulae or R 2' OCO Hal where R 2 , X', p' and q are as defined above and Hal is chlorine, bromine or iodine, to yield a compound of the formula 1 wherein R is lower alkanoyl or a group of the formulae or R 2 0CO, or optionally reacting a compound of the formula 1 where R is lower alkyl and R 1 is formyl, lower alkanoyl or a group of the formula wherein X", p" and q' are as defined above with cyanogen bromide or chloride to yield a compound of the formula 1 wherein R is cyano and R is as hereinbefore described, or optionally removing the cyano group from a compound of the formula 1 wherein R 1 is as defined above and R is cyano by hydrolysis to yield a compound of the formula 1 wherein R is hydrogen, or optionally hydrolyzing a compound of the formula 1 wherein R is a group of the formula to yield a compound of the formula 1 wherein R is a group of the formula wherein n' is as defined above, and optionally preparing in a conventional way the pharmaceutically acceptable salts thereof.