反应详情

A correspondingly R2-substituted 2,4-dichloropyrimidine A-1 (commercially obtainable or prepared by chlorination of the corresponding uracil as described for A-1a by way of example) is dissolved in THF (dioxane, DMA, NMP, acetone or DCM) (approx. 2-5 mL/mmol), 1-1.6 eq Hünig base (triethylamine, potassium carbonate or another suitable base) and the reaction mixture is maintained at a controlled temperature (−78° C. for very reactive pyrimidines, RT or elevated temperature for pyrimidines with a tendency to be less reactive). Then approx. 0.75-1 eq of the amine, dissolved in the corresponding solvent (see above), are added and the reaction mixture is stirred or thawed or heated for a specific time at the corresponding temperature, depending on the reactivity of the pyrimidine used. After the reaction has ended (reaction monitored by HPLC or DC) the reaction mixture is combined with silica gel and all the volatile constituents are eliminated in vacuo. Purification by column chromatography yields the desired substitution products. Depending on the group R2 of the pyrimidine the two possible regioisomers are produced in different ratios. They can generally be separated by chromatography.

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2. temperatureheated for a specific time at the corresponding temperature
3. custom(reaction monitored by HPLC or DC) the reaction mixture
4. customPurification by column chromatography
5. customyields the desired substitution products
6. customare produced in different ratios
7. customThey can generally be separated by chromatography