2,6-Di-tert-butyl-4-methylphenol → 2,4-Diamino-6-methyl-5-[3-(4-chlorophenyl)-3-methyl-1-butenyl]pyrimidine

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Reaction Conditions

Reaction Steps

This compound is prepared in a manner analogous to that of Step E of Example 6, using 4.8 grams (0.014 mole) of 3-methyl-3-(4-chlorophenyl)-1-trimethylstannyl-1-butene, 2.7 grams (0.011 mole) of 2,4-diamino-5-iodo-6-methylpyrimidine (prepared in Step B of Example 3), 2.8 grams (0.066 mole) of lithium chloride, 0.4 gram (5 mole %) of bis(triphenylphosphine)palladium(II) chloride, and about 0.05 gram catalyst) of 2,6-di-tert-butyl-4-methylphenol in 25 mL of N,N-dimethylformamide. After heating at 65° C. for about 2.5 days, the reaction mixture is cooled and diluted with 100 mL of N,N-dimethylformamide. The mixture is filtered, and the filtrate is poured into 300 mL of water. The mixture then is extracted with two 200 mL portions of ethyl acetate. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to a residue. The residue is adsorbed onto silica gel and subjected to column chromatography, using 10% methanol in methylene chloride as the eluant. The product-containing fractions are combined and concentrated under reduced pressure to a residue. NMR analysis of the residue indicates that it is impure product. The residue is subjected to column chromatography on basic alumina (activity II), using 2%, 4%, and 6% methanol in methylene chloride as eluants. The product-containing fractions are combined and concentrated Under reduced pressure, yielding about 2.0 grams of 2,4-diamino-6-methyl-5-[3-(4-chlorophenyl)-3-methyl-1-butenyl]pyrimidine, mp 195°-200° C. The NMR spectrum is consistent with the proposed structure.

Provenance & Evidence