US 5,326,902 A · Oxyalkyne compounds, pharmaceutical compositions containing them and processes for preparing such compounds and compositions

Abstract

Oxyalkyne compounds corresponding to the formula I ##STR1## in which the substituent Y in the meta- or para-position is R.sup.1 represents CH.sub.3 or NH.sub.2, R.sup.2 represents H or CH.sub.3, R.sup.3 represents H, C.sub.1-3 -alkyl or COCH.sub.3, and Ar represents an aromatic residue selected from the group ##STR2## with the proviso that the substituents R.sup.4, R.sup.5 and R.sup.6 are the same or different and each substituent represents H, F, Cl, Br, C.sub.1-6 -alkyl, CF.sub.3 or C.sub.1-6 -alkoxy, and R.sup.7 represents H, F, Cl, Br, C.sub.1-3 -alkyl or CF.sub.3, in the form of their racemates or mixtures of diastereoisomers or in optically active form, which are suitable active ingredients in pharmaceutical compositions.

Claims20

Dependent claims

An oxyalkyne compound corresponding to the formula I ##STR20## wherein the substituent Y in the meta- or para-position is ##STR21## R.sup.1 represents CH.sub.3 or NH.sub.2 ;

R.sup.2 represents H or CH.sub.3 ;
R.sup.3 represents H, C.sub.1-3 -alkyl or COCH.sub.3, and
Ar represents an aromatic residue selected from the group consisting of ##STR22## wherein R.sup.4, R.sup.5 and R.sup.6 are each independently selected from the group consisting of H, F, Cl, Br, C.sub.1-6 -alkyl, CF.sub.3 and C.sub.1-6 -alkoxy, and
R.sup.7 represents H, F, Cl, Br, C.sub.1-3 -alkyl or CF.sub.3 in the form of racemates or mixtures of diastereoisomers or in optically active form.

1 more element

A process for preparing an oxyalkyne compound corresponding to the formula I ##STR23## wherein the substituent Y in the meta- or para-position is ##STR24## R.sup.1 represents CH.sub.3 or NH.sub.2 ;

R.sup.2 represents H or CH.sub.3 ;
R.sup.3 represents H, C.sub.1-3 -alkyl or COCH.sub.3 ;
Ar represents an aromatic residue selected from the group consisting of ##STR25## wherein R.sup.4, R.sup.5 and R.sup.6 are each independently selected from the group consisting of H, F, Cl, Br, C.sub.1-6 -alkyl, CF.sub.3 or C.sub.1-6 -alkoxy, and
R.sup.7 is H, F, Cl, Br, C.sub.1-3 -alkyl or CF.sub.3 ;
said process comprising
reacting an alkyne corresponding to the formula II
Ar--C.tbd.CH
with a partially protected terephthal or isophthal aldehyde corresponding to the formula III ##STR26## wherein R.sup.8 represents CH.sub.3 or CH2CH.sub.3, or both R.sup.8 residues together represent the ethylene group,
in the presence of a base to form an acetal corresponding to the formula IV ##STR27## reacting the resulting acetal with an acid in a water containing solvent to form a hydroxyaldehyde corresponding to the formula V ##STR28## converting the resulting hydroxyaldehyde into an oxime corresponding to the formula VI ##STR29## by either reacting a hydroxy aldehyde of formula V with hydroxyl amine or a salt thereof in the presence of a base, or
substituting the alcoholic proton of the hydroxy aldehyde of formula V with an acid cleavable group which does not react with a Grignard reagent, then reacting the substituted compound of formula V with a methyl magnesium halogenide in an anhydrous nucleophilic solvent to form a secondary alcohol;
oxidizing the resulting secondary alcohol with an oxidizing agent to form a keto compound;
and splitting off the acid cleavable group from the resulting keto compound with an acid to form into a keto compound corresponding to the formula Va ##STR30## reacting the resulting keto compound of formula Va with a hydroxylamine or a salt thereof in the presence of a base to form an oxime corresponding to the formula VI ##STR31## reducing the resulting oxime with a boron-containing reducing agent in the presence of an acid, and optionally a C.sub.1-3 -alcohol, to form a hydroxylamine corresponding to the formula VII ##STR32## wherein R.sup.9 represents H or C.sub.1-3 -alkyl, and converting the resulting hydroxylamine of formula VII into an oxyalkyne compound of formula I by
a) reacting the hydroxylamine of formula VII with trimethylsilyl isocyanate or an alkali cyanate, and hydrolyzing the resulting product, or With phosgene and subjecting the resulting product to aminolysis, or
b) reacting the hydroxylamine of formula VII with an acetylating agent to form a bis-acetyl compound, and treating the resulting acetylated product with a base to split off the O-acetyl group, and optionally converting the propargylic OCOCH.sub.3 -group into an OH-group

11 more elements

Dependencies are inferred from the claim text.

Oxyalkyne compounds, pharmaceutical compositions containing them and processes for preparing such compounds and compositions

Life of this patent

Oxyalkyne compounds, pharmaceutical compositions containing them and processes for preparing such compounds and compositions

Life of this patent

Abstract

Claims20