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

Patent metadata

Field	Value
Publication number	US-9000160-B2
Application number	US-201314022766-A
Country	US
Kind code	B2
Filing date	Sep 10, 2013
Priority date	Sep 14, 2012
Publication date	Apr 7, 2015
Grant date	Apr 7, 2015

Abstract

2-Amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]pyrimidines are manufactured from 4-chloro-2,5-dialkoxypyrimidines in a process that avoids hydrazine and cyanogen halide.

First claim

What is claimed is:

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.

Assignees

• Bland Douglas C
• Roth Gary
• Bott Craig
• Hamilton Christopher T
• Neuman Joseph
• Dow Agrosciences Llc

Inventors

• Bland Douglas C
• Roth Gary
• Bott Craig
• Hamilton Christopher T
• Neuman Joseph

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D239/52 Primary

  Two oxygen atoms · CPC title

• C08F10/06

  Propene · CPC title

• C08F4/657

  with metals or metal-containing compounds, not provided for in groups C08F4/653 - C08F4/656 · CPC title

• C08F4/651

  Pretreating with non-metals or metal-free compounds · CPC title