Process for the preparation of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine from 4-chloro-2,5-dimethoxypyrimidine

1. A process for the preparation of 2-amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]-pyrimidines of the formula (I),

wherein R is C 1 -C 4 alkyl

comprising:

i) contacting a 4-chloro-2,5-dialkoxypyrimidine of the formula

wherein R is as previously defined

with a salt of cyanamide in a polar aprotic solvent to provide a 2,5-dialkoxy-4-cyanoaminopyrimidine of the formula

in which R is as previously defined;

ii) contacting the 2,5-dialkoxy-4-cyanoaminopyrimidine with either hydroxylamine as a free base or hydroxylamine salt in the presence of a base to provide a 2,5-dialkoxy-4-hydroxyguanidinylpyrimidine of the formula

wherein R is as previously defined; and

iii) cyclizing the 2,5-dialkoxy-4-hydroxyguanidinylpyrimidine by treating with an alkyl chloroformate to provide the 2-amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]pyrimidine.

2. The process of claim 1 , wherein R is CH 3 .

3. The process of claim 1 , wherein the 2,5-dialkoxy-4-hydroxyguanidinyl-pyrimidine of step ii) is used without isolation to prepare the 2-amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]pyrimidine in step iii).

4. The process of claim 1 , wherein the salt of cyanamide is an alkali metal salt or alkaline earth metal salt.

5. The process of claim 1 , wherein the salt of cyanamide is sodium hydrogen cyanamide.

6. The process of claim 1 , wherein the polar aprotic solvent of (i) is acetonitrile or N-methyl-2-pyrrolidinone.

7. The process of claim 1 , wherein (i) is performed at a temperature of from about 0° C. to about 60° C.

8. The process of claim 1 , wherein the free base of hydroxylamine salt of (ii) is a sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, or a trialkylamine salt.

9. The process of claim 1 , wherein (ii) is performed in a polar solvent.

10. The process of claim 9 , wherein the solvent is methanol, ethyl acetate, or acetonitrile.

11. The process of claim 1 , wherein (ii) is performed at a temperature of from about 0° C. to about 80° C.

12. The process of claim 1 , wherein the alkylchloroformate of (iii) is a methyl chloroformate.

13. The process of claim 1 , wherein (iii) is performed in the presence of a base.

14. The process of claim 13 , wherein the base is sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, or triethylamine.

15. The process of claim 1 , wherein (iii) is performed at a temperature of from about 45° C. to about 100° C.

16. The process of claim 1 , wherein (iii) is performed in a polar aprotic solvent.

17. The process of claim 16 , wherein the solvent is ethyl acetate or acetonitrile.

18. A process for the preparation of 2-amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]-pyrimidines of the formula (I),

wherein R is C 1 -C 4 alkyl

comprising:

cyclizing a 2,5-dialkoxy-4-hydroxyguanidinylpyrimidine

of the formula

wherein R is as previously defined;

by treating with an alkyl chloroformate to provide the 2-amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]pyrimidine.

19. The process of claim 18 , wherein the 2,5-dialkoxy-4-hydroxyguanidinylpyrimidine is formed by contacting a 2,5-dialkoxy-4-cyanoaminopyrimidine of the formula

in which R is as previously defined

with either hydroxylamine as a free base or hydroxylamine salt in the presence of a base to provide a 2,5-dialkoxy-4-hydroxyguanidinylpyrimidine.

20. A compound of the formula

in which R represents C 1 -C 4 alkyl.

21. A compound of the formula

in which R represents C 1 -C 4 alkyl.