Facile process for the preparation of high-purity aminopterin
View Patent ↗A process for the preparation of aminopterin with a purity greater than 90%, which comprises reacting folic acid, with a silazane in an organic solvent at a temperature from 60 to 180° C., the said solvent being a tertiary amine organic solvent, or, if a catalyst which is acid in nature is present, a basic organic solvent or acetonitrile, and further adding water such that there is about 2.8 to 7.0 mole water for each mole of folic acid.
1. A process for the preparation of aminopterin with a purity greater than about 90%, which comprises reacting folic acid, with a silazane in an organic solvent at a temperature from 60 to 180° C., the said solvent being a tertiary amine organic solvent, or, if a catalyst which is acid in nature is present, a basic organic solvent or acetonitrile, and adding water such that there is about 2.8 to 7.0 mole water for each mole of folic acid.
2. Process according to claim 1 , wherein the purity is greater than about 93%.
3. Process according to claim 1 , wherein the purity is greater than about 95%.
4. Process according to claim 1 , wherein the purity is greater than about 98%.
5. Process according to claim 1 , wherein the silazane used is hexamethyldisilazane.
6. Process according to claim 1 , wherein 5 to 15 moles of silazane are used per mole of folic acid.
7. Process according to claim 1 , wherein the basic organic solvent used is pyridine, N,N-dimethylaniline or quinoline.
8. Process according to claim 1 , wherein the aminopterin is isolated as a metal salt.
9. Process according to claim 1 , wherein the reaction is carried out in the presence of a catalyst which is acid in nature in a basic organic solvent or in acetonitrile.
10. Process according to claim 9 , wherein the catalyst is an inorganic or organic acid, an organic or inorganic ammonium salt or a Lewis acid.
11. Process according to claim 9 , wherein the catalyst is ammonium chloride, sulfate or formate, pyridinium p-toluenesulfonate or hydrochloride or N-methylanilinium trifluoroacetate.
12. Process according to claim 9 , wherein the acidic catalyst is pyridinium p-toluenesulfonate and the solvent is acetonitrile.
13. A process for the preparation of aminopterin with a purity greater than 90%, which comprises reacting folic acid, with a silazane in an organic solvent at a temperature from 60 to 180° C., the said solvent being a tertiary amine organic solvent, or, if a catalyst which is acid in nature is present, a basic organic solvent or acetonitrile, wherein the improvement consists of adding water such that there is about 2.8 to 7.0 mole water for each mole of folic acid.
14. A process according to claim 13 , wherein there is about 2.8 to 3.2 mole water for each mole of folic acid.
15. A process according to claim 13 , wherein there is about 3.0 mole water for each mole of folic acid.
16. Process according to claim 13 , wherein the purity is greater than about 93%.
17. Process according to claim 13 , wherein the purity is greater than about 95%.
18. Process according to claim 13 , wherein the purity is greater than about 98%.