Process for the preparation of 5-substituted-8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amines
View Patent ↗5-Substituted-8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amines are manufactured from 2-substituted-4-amino-5-methoxypyrimidines in a process that avoids hydrazine and cyanogen halide.
1. A process for the preparation of 5-substituted-8-alkoxy[1,2,4]triazolo[1,5-c]-pyrimidin-2-amines of the formula (I),
in which
X represents halogen or OR; and
R represents C 1 -C 4 alkyl;
which comprises:
i) contacting a 2-substituted-4-amino-5-alkoxypyrimidine of the formula
in which X and R are as previously defined
with an isothiocyanatidocarbonate of the formula
in which R is as previously defined,
in a polar aprotic solvent to provide a (pyrimidinylamino)carbonothioylcarbamate of the formula
in which X and R are as previously defined;
ii) contacting the (pyrimidinylamino)carbonothioylcarbamate with hydroxylamine in the presence of a base to provide a (pyrimidinylamino)hydroxyimino)methylcarbamate of the formula
in which X and R are as previously defined; and
iii) cyclizing the (pyrimidinylamino)hydroxyimino)methylcarbamate by heating in an inert solvent to provide the 5-substituted-8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amine.
2. The process of claim 1 in which X and R both represent OCH 3 .
3. The process of claim 1 in which the (pyrimidinylamino)(hydroxyimino)-methylcarbamate of step ii) is used without isolation to prepare the 2-amino-5-substituted-8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine in step iii).
4. A process for the preparation of 2-amino-5,8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidines of the formula
in which
R represents C 1 -C 4 alkyl;
which comprises contacting a 5-halo-8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amine of the formula
in which
X represents halogen; and
R represents C 1 -C 4 alkyl
with an alkali metal alkoxide in an alcoholic solvent.