Compositions comprising folic acid derivatives, their preparations and methods of use
Described herein are methods for making folic acid derivatives, intermediates, pharmaceutical compositions and uses thereof.
1. A method of making a compound of formula (I):
the method comprising cyclizing a compound of formula (II)
to make a compound of formula (V)
and reducing the compound of formula (V) to make the compound of formula (I),
wherein
R 1 and R 2 are each independently selected from H, OH, NH 2 , C 1-6 alkyl or aryl;
R 3 is H, C 1-6 alkyl or aryl;
Y is halo; and
X is Na, K, Mg or Ca.
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 R 1 is NH 2 , R 2 is OH and R 3 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.