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

Temperature

-78 °C

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.

1. stirringthe resulting mixture was stirred at −78° C. for 1 hour
2. customThe mixture then was quenched at −78° C. by the addition of 1 mL of methanol
3. temperatureThe mixture was then warmed to room temperature
4. custompartitioned between saturated aqueous sodium bicarbonate and ethyl acetate
5. customThe layers were separated
6. extractionthe aqueous layer was extracted once more with ethyl acetate
7. dry with materialThe combined organics were dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customPurification via silica gel chromatography (ethyl acetate/hexanes)

ORD record

ord-f00749a5bdc146f099f763f8fc8eaedf

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08551984B2