Pharmaceutical process and intermediates
The present disclosure provides for processes and intermediates in the large-scale manufacture of the compound of formula (I) or hydrates thereof.
1. A compound which is a triethylammonium salt of the compound of formula (II)
2. The compound according to claim 1 , wherein the stoichiometric ratio of triethylamine to the compound of formula (II) is between 0.5:1 and 2.5:1.
3. The compound according to claim 2 the stoichiometric ratio of triethylamine to the compound of formula (II) is between 1.5:1 and 2.5:1.
4. The compound according to claim 2 the stoichiometric ratio of triethylamine to the compound of formula (II) is about 2:1.
5. The compound according to claim 1 that is the bis(triethylammonium) salt of the compound of formula (II).
6. The compound according to claim 2 that is the bis(triethylammonium) salt of the compound of formula (II).
7. The compound according to claim 3 that is the bis(triethylammonium) salt of the compound of formula (II).
8. The compound according to claim 4 that is the bis(triethylammonium) salt of the compound of formula (II).
9. A method forming an amine salt of the compound of formula (II)
comprising,
(i) combining a solution of the amine in a polar solvent and water with an amide solvate of the compound of formula (II); and
(ii) filtering the reaction mixture.
10. The method of claim 9 wherein the polar solvent is selected from an alcohol, acetone, acetonitrile and dimethylsulfoxide.
11. The method of claim 10 , wherein the polar solvent is isopropanol.
12. The method of claim 9 , wherein the formation of the amine salt is carried out at a temperature not exceeding 70° C.
13. The method of claim 10 , wherein the formation of the amine salt is carried out at a temperature in the range of from about 0° C. to not exceeding 60° C.
14. The method of claim 10 , wherein the formation of the amine salt is carried out at a temperature in the range of from about 0° C. to not exceeding 50° C.
15. The method of claim 10 , wherein the formation of the amine salt is carried out at a temperature in the range of from about 0° C. to not exceeding 40° C.
16. The method of claim 10 , wherein the formation of the amine salt is carried out at a temperature in the range of from about 0° C. to not exceeding 30° C.
17. The method of claim 10 , wherein the formation of the amine salt is carried out at a temperature in the range of from about 0° C. to not exceeding 20° C.
18. The method of claim 10 , wherein the formation of the amine salt is carried out at a temperature in the range of from about 0° C. to not exceeding 10° C.
19. The method of claim 10 , wherein the formation of the amine salt is carried out at a temperature in the range of from about 10° C. to about 30° C.
20. The method of claim 10 , wherein the formation of the amine salt is carried out at ambient temperature.