A

1. A process for the preparation of a compound of Formula I:

wherein:

R 1 and R 2 are independently optionally substituted alkyl;

X is pyrazol-4-yl;

Y is a covalent bond or lower alkylene; and

Z is optionally substituted monocyclic aryl or optionally substituted monocyclic heteroaryl;

comprising;

cyclizing a compound of the formula (3):

wherein R 1 , R 2 , X, Y, and Z are as defined above.

2. The process of claim 1 , wherein the compound of formula (3) is cyclized in an inert solvent in the presence of a base.

3. The process of claim 2 , wherein the inert solvent is methanol and the base is aqueous sodium hydroxide solution.

4. The process of claim 3 , wherein R 1 and R 2 are independently lower alkyl, Y is methylene, and Z is optionally substituted phenyl.

5. The process of claim 4 , wherein R 1 is n-propyl, R 2 is ethyl, and Z is 3-trifluoromethylphenyl.

6. The process of claim 1 , wherein the compound of formula (3):

is prepared by a method comprising contacting a compound of the formula (2);

with a compound of the formula Z-Y—X—CO 2 H in the presence of a carbodiimide or with a compound of the formula Z-Y—X—C(O)Hal, where Hal is chloro or bromo.

7. The process of claim 6 , wherein the compound of formula (3) is reacted with a compound of the formula Z-Y—X—CO 2 H in methanol.

8. The process of claim 7 , wherein the carbodiimide is 1-(3)-dimethylaminopropyl-3-ethylcarbodiimide.

9. The process of claim 6 , wherein the compound of formula (3) is reacted with a compound of the formula Z-Y—X—C(O)Cl.

10. The process of claim 9 , wherein the reaction is carried out in an inert solvent in the presence of a tertiary base.

11. The process of claim 10 , wherein the inert solvent is acetonitrile and the tertiary base is triethylamine.

12. The process of claim 6 , wherein R 1 and R 2 are independently lower alkyl, X is pyrazol-4-yl, Y is methylene, and Z is optionally substituted phenyl.

13. The process of claim 12 , wherein R 1 is n-propyl, R 2 is ethyl, and Z is 3-trifluoromethylphenyl, namely 3-ethyl-1-propyl-8-{1-[(3-trifluoromethylphenyl)methyl]pyrazol-4yl}-1,3,7-trihydropurine-2,6-dione.

14. The process of claim 1 , wherein the compound of the formula:

is prepared by a method comprising contacting a compound of the formula;

with a compound of the formula R 1 L, in which L is a leaving group.

15. The process of claim 14 , wherein R 1 is lower alkyl optionally substituted by cycloalkyl, and L is iodo.

16. The process of claim 15 , wherein the reaction is carried out in the presence of a base in an inert solvent.

17. The process of claim 16 , wherein to base is potassium carbonate and the inert solvent is N,N-dimethylformamide.

18. The process of claim 17 , wherein R 1 and R 2 are independently lower alkyl, X is pyrazol-4-yl, Y is methylene, and Z is optionally substituted phenyl.

19. The process of claim 18 , wherein R 1 is n-propyl, R 2 is ethyl, and Z is 3-trifluoromethylphenyl.

20. The process of claim 1 , wherein the compound of the formula:

is prepared by a method comprising contacting a compound of the formula;

with a compound of the formula R 2 L, in which L is a leaving group.

21. The process of claim 20 , wherein R 2 is lower alkyl optionally substituted by cycloalkyl, and L is iodo.

22. The process of claim 21 , wherein the reaction is carried out in the presence of a base in an inert solvent.

23. The process of claim 22 , wherein the base is potassium carbonate and the inert solvent is N,N-dimethylformamide.

24. The process of claim 23 , wherein R 1 and R 2 are independently lower alkyl, X is pyrazol-4-yl, Y is methylene, and Z is optionally substituted phenyl.

25. The process of claim 24 , wherein R 1 is n-propyl, R 2 is ethyl, and Z is 3-trifluoromethylphenyl.

26. The process of claim 14 , wherein the compound of the formula:

is prepared by a method comprising contacting a compound of the formula:

with a compound of the formula Z-Y—X—CO 2 H in the presence of a carbodiimide or with a compound of the formula Z-Y—X—C(O)Hal, where Hal is chloro or bromo.

27. The process of claim 26 , wherein the compound of formula (15) is reacted with a compound of the formula Z-Y—X—CO 2 H in methanol.

28. The process of claim 27 , wherein the carbodiimide is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.

29. The process of claim 26 , wherein the compound of formula (15) is reacted with a compound of the formula Z-Y—X—C(O)Cl.

30. The process of claim 29 , wherein the reaction is carried out in an inert solvent in the presence of a tertiary base.

31. The process of claim 30 , wherein the inert solvent is acetonitrile and the tertiary base is triethylamine.

32. The process of claim 31 , wherein R 1 and R 2 are independently lower alkyl, X is pyrazol-4-yl, Y is methylene, and Z is optionally substituted phenyl.

33. The process of claim 32 , wherein R 1 is n-propyl, R 2 is ethyl, and Z is 3-trifluoromethylphenyl.

34. The process of claim 19 , wherein the compound of the formula:

is prepared by a method comprising contacting a compound of the formula:

with a compound of the formula Z-Y—X—CO 2 H in the presence of a carbodiimide or a compound of the formula Z-Y—X—C(O)Hal, where Hal is chloro or bromo.

35. The process of claim 34 , wherein the compound of formula (12) is reacted with a compound of the formula Z-Y—X—CO 2 H in methanol.

36. The process of claim 35 , wherein the carbodiimide is 1-(3-dimethylaminopropy)-3-ethylcarbodiimide.

37. The process of claim 34 , wherein the compound of formula (12) is reacted with a compound of the formula Z-Y—X—C(O)Cl.

38. The process of claim 37 , wherein the reaction is carried out in an inert solvent in the presence of a tertiary base.

39. The process of claim 38 , wherein the inert solvent is acetonitrile and the tertiary base is triethylamine.

40. The process of claim 39 , wherein R 1 and R 2 are independently lower alkyl, X is pyrazol-4-yl, Y is methylene, and Z is optionally substituted phenyl.

41. The process of claim 40 , wherein R 1 is n-propyl, R 2 is ethyl, and Z is 3-trifluoromethylphenyl.

42. The process of claim 34 , wherein the compound of the formula:

is prepared by a method comprising the steps of:

a) contacting a compound of the formula:

with hexamethyldisilazane in the presence of an acid catalyst;

b) contacting the product thus formed with R 1 L, where L is a leaving group, followed by;

c) contacting the product thus formed:

with a mixture of sodium nitrite in acetic acid/water; and

d) contacting the product thus formed:

with a mixture of aqueous ammonia and sodium dithionite.

43. The process of claim 42 , wherein in step a) R 1 is lower alkyl, L is iodo, and the acid catalyst is ammonium sulfate.

44. The process of claim 26 , wherein the compound of the formula;

is prepared by a method comprising the steps of:

a) contacting a compound of the formula:

with ethyl cyanoacetate in the presence of a base in a protic solvent;

b) contacting the product thus formed:

with a mixture of sodium nitrite in acetic acid/water; and

c) contacting the product thus formed:

with a mixture of aqueous ammonia and sodium dithionite.

45. The process of claim 44 , wherein the base is sodium ethoxide and the protic solvent is ethanol.

46. The process of claim 6 , wherein the compound of formula:

is prepared by a method comprising the steps of:

a) contacting a compound of the formula:

with ethyl cyanoacetate in the presence of a base in a protic solvent;

b) contacting the product thus formed:

with the dimethylacetal of N,N-dimethylformamide;

c) contacting the product thus formed:

with a compound of formula R 1 L, in which L is a leaving group;

d) contacting the product thus formed:

with aqueous ammonia;

e) contacting the product thus formed:

with a mixture of sodium nitrite in acetic acid/water; and

f) contacting the product thus formed:

with a mixture of aqueous ammonia and sodium dithionite.

47. The process of claim 46 , wherein the base is sodium ethoxide and the protic solvent is ethanol.