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

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Reaction Steps

Under a nitrogen atmosphere, a stirring solution of 4.2 grams (0.009 mole) of 3-(4-fluorophenyl)-3-methyl-1-tributylstannyl-1-butene, 1.9 grams (0.077 mole) of 2,4-diamino-5-iodo-6-methylpyrimidine (prepared in Step B of Example 3), 2.0 grams (0.046 mole) of lithium chloride, 0.4 gram (catalyst) of bis(triphenyl phosphine)palladium(II) chloride, and about 0.05 gram (catalyst) of 2,6-di-tert-butyl-4-methylphenol in 80 mL of N,N-dimethylformamide is heated at 65° C. for about 2.5 days. After this time the reaction mixture is cooled and poured into 500 mL of water. The mixture then is extracted with three 100 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 subjected to column chromatography on basic alumina (containing 6% water), 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 an impure product. The residue is subjected to column chromatography on silica gel, using 10% methanol in methylene chloride as the eluant. The product-containing fractions are combined and concentrated under reduced pressure, yielding about 0.6 gram of 2,4-diamino-6-methyl-5-[3-(4-fluorophenyl)-3-methyl-1-butenyl]pyrimidine, mp 164°-168° C. (Compound 66). The NMR spectrum is consistent with the proposed structure.

Provenance & Evidence