Process for the preparation of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine from 4-amino-2,5-dimethoxypyrimidine
View Patent ↗5-Substituted-8-alkoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amines are manufactured from 4-amino-2,5-dialkoxypyrimidines in an improved process in which the generation of gaseous by-products is controlled by the continuous addition of hydroxylamine as a free base.
1. A process for the preparation of 2-amino-5,8-dialkoxy[1,2,4]triazolo[1,5-c]-pyrimidines of the formula (I),
in which R is C 1 -C 4 alkyl
comprising continuously adding to a [(2,5-dialkoxypyrimidin-4-yl)amino]carbono-thioylcarbamate of the following formula:
in which R is as previously defined
in a polar or nonpolar aprotic solvent an aqueous solution of hydroxylamine free base at a temperature from about 60° C. to about 110° C. at a rate slow enough to safely handle the release of gaseous by-products.
2. The process of claim 1 , wherein R is CH 3 .
3. The process of claim 1 , wherein the aprotic solvent is nonpolar.
4. The process of claim 1 , wherein the aprotic solvent is toluene.
5. The process of claim 1 , wherein said temperature is at least 80° C.
6. The process of claim 1 , wherein the [(2,5-dialkoxypyrimidin-4-yl)amino]carbono-thioylcarbamate is formed by contacting a 4-amino-2,5-dialkoxypyrimidine of the formula
in which R is as previously defined
with a C 1 -C 4 alkoxy carbonylisothiocyanate of the formula
S═C═N—C(O)OR
wherein R is as previously defined,
in a polar or nonpolar aprotic solvent at a temperature from about 60° C. to about 110° C.
7. The process of claim 6 , wherein R represents CH 3 .
8. The process of claim 6 , wherein the aprotic solvent is nonpolar.
9. The process of claim 6 , wherein the aprotic solvent is toluene.
10. The process of claim 6 , wherein the temperature of step (i) and (ii) is at least 60° C.
11. The process of claim 6 , wherein the temperature of step (i) and (ii) is at least 80° C.