Dimethylformamide → 5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carbaldehyde

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Reaction Conditions

Reaction Steps

Lithium diisopropylamide (1.8M in tetrahydrofuran, 25 ml, 4.46 mmol) was added dropwise to a cooled −78° C. solution of INTERMEDIATE 4 (500 mg, 1.49 mmol) in tetrahydrofuran (7.5 ml). The mixture was stirred at −78° C. for 35 minutes. N,N-dimethylformamide (230 μl, 2.97 mmol) was added, and the resulting mixture was stirred at −78° C. for 1 hour. The mixture then was quenched at −78° C. by the addition of 1 mL of methanol. The mixture was then warmed to room temperature and partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (ethyl acetate/hexanes) afforded 5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazole-2-carbaldehyde (464 mg, 1.27 mmol, 86% yield) as a yellow solid. ESI: [M+H]+ m/z 365.0.

Provenance & Evidence