Compositions comprising folic acid derivatives, their preparations and methods of use

• US 9,382,251 B2
• Filed: 07/26/2013
• Issued: 07/05/2016
• Est. Priority Date: 07/27/2012
• Status: Active Grant

• Current Assignee: JSB Pharma Development LLC
• Original Assignee: Chemic Laboratories, Inc. (Solvias AG)
• Inventors: Jones, Gerald S. Jr., St. Laurent, Joseph P., Goodrich, Scott A.
• Primary Examiner(s): Leeser, Erich A
• Application Number:
  US14/417,504
• Publication Number:
  US 20150210695A1
• Time in Patent Office: 1,075 Days
• Field of Search: 514/267, 544/251
• US Class Current: 1/1
• 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 of making a compound of formula (I):

2. The method of claim 1, wherein the reduction of a compound of formula (V) is carried out in the presence of a reducing agent.

3. The method of claim 1, wherein the reduction step further comprises a strong base.

4. The method of claim 1, wherein the reduction step is carried out in the presence of a solvent.

5. The method of claim 1, wherein R¹ is NH₂, R² is OH and R³ is H.

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

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

8. The method of claim 7, further comprising a strong acid.

9. The method of claim 7, further comprising a solvent.

10. The method of claim 1, wherein Y is Cl.