COMPOSITIONS COMPRISING FOLIC ACID DERIVATIVES, THEIR PREPARATIONS AND METHODS OF USE

• US 20190315749A1
• Filed: 02/28/2019
• Published: 10/17/2019
• Est. Priority Date: 07/27/2012
• Status: Active Grant

• Current Assignee: JSB Pharma Development LLC
• Original Assignee: Chemic Laboratories, Inc. (Solvias AG)
• Inventors: Jones, Jr., Gerald S., St. Laurent, Joseph P., Goodrich, Scott A.
• Granted Patent: US 10,590,138 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: C07D 475/04 with a nitrogen atom directly attached in position 2
• CPC Class Codes: C07D 487/14 Ortho-condensed systems

Abstract

Described herein are methods for making folic acid derivatives, intermediates, pharmaceutical compositions and uses thereof.

Claims

1. A method for making a compound of formula (V):

2. The method of claim 1, wherein the cyclization step is carried out in the presence of formic acid.

3. The method of claim 2, further comprising a strong acid.

4. The method of claim 3, wherein the strong acid is HCl.

5. The method of claim 2, further comprising a solvent.

6. The method of claim 5, wherein the solvent is an aqueous solvent.

7. The method of claim 1, wherein R¹ is NH₂.

8. The method of claim 1, wherein R² is OH.

9. The method of claim 1, wherein R³ is H.

10. The method of claim 1, wherein X is Ca.

11. The method of claim 1, wherein Y is CL.

12. The method of claim 1, wherein R¹ is NH₂, R² is OH, R³ is H, X is Ca, and Y is Cl.

13. The method of claim 1, the method further comprising a reduction of a compound of formula (V) to make a compound of formula (I):