反应详情

The patent of Ellard, U.S. Pat. No. 4,080,325, is believed uniquely to be the closest art. Of interest is that the struggle for the production of methotrexate has been assisted by the U.S. Government in the effort to bring this compound in sufficient amount to clinical trial. Relative to the present application, the pertinent passages in U.S. Pat. No. 4,080,325 appear to be column 1, lines 55-68, as well as the equation noted at column 2. The optimum pH was 5.5 to give the desired 6-hydroxymethylpteridine isomer used in the reaction. The relationship of the unwanted isomers is shown in the equation at column 2, lines 40-50. It was found that the reaction time from the parameters given in the patent might be reduced to 3-6 hours and yields increased to 60-75% of the desired isomer 2,4-diamino-6-hydroxymethylpteridine. Reaction pH is lowered from about 5.4 to 3.5 or optimally 3.0. The reaction is complete in 3-6 hours and the yield is 60-65% with an isomer ratio (2,4-diamino-6-hydroxymethylpteridine/2,4-diamino-7-hydroxymethylpteridine) of approximately 20:1. Comparison aeration with air instead of oxygen at a comparable pH, say 3.5, has been shown to yield an abundance of 2,4-diamino-6-methylpteridine rather than the desired 2,4-diamino-6-hydroxymethylpteridine.

1. customused in the reaction
2. customyields
3. customReaction pH
4. waitThe reaction is complete in 3-6 hours