ES466968A1 - Heterocyclic nitrogen compound and process for preparing same - Google Patents

Abstract

Procedure for the preparation of pyrazolo-oxazepines and pyrazolo-thiazepines of the formula ** (See formula) ** where X means an oxygen or sulfur atom, R1 means hydrogen or one or more groups, the same or different, alcohol with -4 carbon atoms, alkoxy with 1-4 carbon atoms, alcohol mercapto with 1-4 atoms of carbon, halogen, trifluoromethyl, nitro, carboxy, alkoxycarbonyl with 1-4 carbon atoms in the alkoxy group, dialkoxylamino with 1-4 carbon atoms in the alcoholic groups, amidino, the -SO2NH2 group and the -CH2-COCR group, R denoting hydrogen or an alcohol radical with 1-5 carbon atoms, which may be attached to each of the available positions of the phenyl radical; R2 means an alcohol radical with 1-4 carbon atoms, cycloalkoxy with 5-7 carbon atoms, benzyl or phenyl, the phenyl radical being able to be substituted with the R1 substituents; R3 signifies hydrogen, an alcohol radical with 1-4 carbon atoms, cycloalkoxy with 5-7 carbon atoms, benzyl or phenyl, which may be substituted with substituents R1; R4 signifies hydrogen or an alcohol group with 1-4 atoms of carbon, which in turn may be substituted with a dialkoxy amino group with 1-4 carbon atoms in the alcohol groups, with a carboxy or alkoxycarbonyl group with 1-4 carbon atoms in the alkoxy group, with a nitrile group or with a imidazolin-2-yl group, or an imidazolin-2-yl radical, or an acyl radical of the formula ** (See formula) ** , where it is n = 0, 1, 2, and R5 can be chloro, alkoxyloxy with 1-4 carbon atoms, the alcohol group being able to be substituted with a dialkoylamino group with 1-4 carbon atoms in the alcohol groups, and in which if n = 0, R5 can be an amino or hydrazino group, or an alkylated or acylated hydrazino group, and in which R5 can also mean the radical (see formula), in which R6 and R7 are the same or different, and represent hydrogen or an alcohol radical with 1 to 6 carbon atoms, which may be substituted with hydroxy and/or mono- or di-alcoholic groups with 1-4 carbon atoms in the alcohol groups, and may also form the alcohol radicals together with the nitrogen atom a ring with 5 to 8 members, and in which one of the carbon atoms can be replaced by an oxygen, sulfur or nitrogen atom, the hydrogen atom can be replaced together with the last one an alcohol group with 1-4 carbon atoms, which may be substituted with the hydroxy, ethylenedioxy or trimethylenedioxy groups, or with the phenyl group, as well as their physiologically compatible salts, characterized in that (a) a 5-halogen-pyrazole-4-carbaldehyde of formula II ** (See formula) ** where Hal means chlorine or bromine, and R2 and R3 have the meanings mentioned for formula I, are reacted with an ortho-aminophenol (X = 0) or with an ortho-amino-thiophenol (X = S) of the formula III ** (See formula) ** wherein R1 has the meaning mentioned for formula I, and (b) optionally the reaction product is reduced to form the compound ** (See formula) ** and (C1) this compound is optionally reacted with a compound of the formula YR8, in which Y represents chlorine or bromine, and R8 means an alkoxycarbonyl group with 1-4 carbon atoms in the alkoxy group or an alcohol group with 1-4 carbon atoms, which may be substituted with a dialeohylamino group with 1-4 carbon atoms in the alcohol groups, with a carboxy group, an alkoxycarbonyl group with 1-4 carbon atoms in the alkoxy group, a group cyano or an imidazolin-2-yl group, or (C2) is transformed with formaldehyde/potassium cyanide into a cyanomethyl compound, and then, with 1,2-diaminoethane, a 5-imidazolin-2-yl-methyl compound I is prepared, or (C3) with benzoyl isothiocyanate, a benzoylthiourea is prepared, which is transformed in a known way into an imidazolin-2-yl compound I, or (C ^) is reacted with acid chlorides, acid anhydrides or phosgene, obtaining with bifunctional acid derivatives composed of structure V ** (See formula) ** with n = 0, 1 or 2, which are reacted with ammonia, hydrazine, alcohols or amines ** (See formula) ** where R9 and R10 have the meaning of R6 and R7. (Machine-translation by Google Translate, not legally binding)