Thiazolyl-pyrazolopyrimidine compounds as synthetic intermediates and related synthetic processes
The present invention relates to a synthetic intermediate of the formula: and its use in a synthetic process to make compounds of the formula
1. A compound of the formula
wherein:
R 1 and R 2 are independently ethyl or n-propyl;
or a salt thereof.
2. The compound according to claim 1 , or a salt thereof, wherein R 1 and R 2 are each ethyl.
3. A synthetic process for preparing a compound of the formula
wherein R 1 and R 2 are independently ethyl or n-propyl,
comprising the steps of
i) reacting a compound of the formula
or a salt thereof, with 2,4-di-chlorothiazole, or a salt thereof, in the presence of a copper halide catalyst, a ligand selected from 1,10-phenanthroline and bipyridine, and a base selected from K 3 PO 4 and Cs 2 CO 3 , in the presence of a suitable solvent, to form a compound of the formula
ii) reacting the product of step i), with morpholine, or a salt thereof, in the presence of a suitable inorganic base and solvent.
4. The process according to claim 3 wherein R 1 and R 2 are each ethyl.
5. The process according to claim 3 wherein the copper halide is CuCl.
6. The process according to claim 3 wherein the ligand is 1,10-phenanthroline.
7. The process according to claim 3 wherein the base in step i) is Cs 2 CO 3 .
8. The process according to claim 3 wherein the base in step ii) is K 2 CO 3 .
9. The process according to claim 3 wherein R 1 and R 2 are each ethyl, the copper halide is CuCl, the ligand is 1,10-phenanthroline, the base in step i) is Cs 2 CO 3 , and the base in step ii) is K 2 CO 3 .
10. The process according to claim 9 wherein the solvent for step i) is 1,4-Dioxane or 2-MeTHF/DMAC and the solvent for step ii) is morpholine, 2-MeTHF, or 2-propanol.
11. A synthetic process for preparing a compound of the formula
wherein R 1 and R 2 are independently ethyl or n-propyl,
comprising the steps of
i) reacting a compound of the formula
or a salt thereof, with excess morpholine or salt thereof, in the presence of a suitable solvent.
12. The process of claim 11 wherein the solvent is 2-methyl tetrahydrofuran.
13. The process of claim 11 wherein the solvent is 2-propanol.
14. The process of claim 11 wherein R 1 and R 2 are each ethyl.
15. A synthetic process for preparing a compound of the formula
wherein R 1 and R 2 are independently ethyl or n-propyl,
comprising the steps of
i) reacting a compound of the formula
or a salt thereof, with 2,4-di-chlorothiazole, or a salt thereof, in the presence of a copper halide catalyst, a ligand selected from 1,10-phenanthroline and bipyridine, and a base selected from K 3 PO 4 and Cs 2 CO 3 , to form a compound of the formula
ii) reacting the product of step i), with an excess of morpholine, or a salt thereof, in a suitable solvent.
16. The process of claim 15 wherein the solvent is 2-methyl tetrahydrofuran.
17. The process of claim 15 wherein the solvent is 2-propanol.
18. The process of claim 15 wherein R 1 and R 2 are each ethyl.