Methoxymethyl-triphenylphosphonium chloride → N-(3-{2-[(E)-2-methoxyethenyl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Temperature

0 °C

A solution of potassium tert-butoxide (429 mg, 3.82 mmol) in tetrahydrofuran (2 ml) was added dropwise to a cooled −78° C. solution of (methoxymethyl)triphenylphosphonium chloride (1.31 g, 3.82 mmol) in tetrahydrofuran (6 ml). The mixture was warmed to 0° C. and stirred for 20 minutes. A solution of the product of Step 1 (464 mg, 1.27 mmol) in THF (4 ml) was then added, and the resulting mixture was stirred at 0° C. for 1 hour and then warmed to room temperature and stirred overnight. The mixture was then partitioned between saturated aqueous ammonium chloride 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 N-(3-{2-[(E)-2-methoxyethenyl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (98 mg, 0.25 mmol, 19% yield) as a yellow solid. MS ESI: [M+H]+ m/z 393.1. 1H NMR (500 MHz, DMSO-d6) δ 10.23 (s, 1H), 8.80 (d, J=4.0 Hz, 1H), 7.91 (s, 1H), 7.90 (s, 1H), 7.56 (d, J=10.5 Hz, 1H), 7.41 (s, 1H), 7.26 (d, J=4.0 Hz, 1H), 7.11 (s, 1H), 6.14 (d, J=10.5 Hz, 1H), 3.69 (s, 3H), 2.28 (s, 3H). rhSYK activity=+++

1. stirringthe resulting mixture was stirred at 0° C. for 1 hour
2. temperaturewarmed to room temperature
3. stirringstirred overnight
4. customThe mixture was then partitioned between saturated aqueous ammonium chloride 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-16964b0aa4d94d1082f9ee66328b9927

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759366B2