| 摘要 |
The invention relates to a method for preparing N-[4-[[(2,4-diamino-6-pteridinyl)-methyl]-methylamino]benzoyl]glutamic acid (methotrexate), wherein diethyl N-[4-methylamino)benzoyl]glutamate of formula II <CHEM> is alkylated with 2,4-diamino-6-chloromethylpteridine hydrochloride of formula I <CHEM> in a polar aprotic solvent in the presence of potassium iodide whereafter the resulting hydroiodide of diethyl N-[4-[[(2,4-diamino-6-pteridinyl)-methyl]methylamino]benzoyl]glutamate of formula III <CHEM> is hydrolyzed, either directly or after neutralization to III, to yield N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]glutamate acid (methotrexate) of formula V <CHEM> Methotrexate (N-[4-[[(2,4-diamino-6-pteridinyl)-methyl]methylamino]-benzoyl]glutamic acid) is a well known antineoplastic agent useful in the treatment of acute leukemia and other cancerous diseases. |
