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

Temperatur

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-Eintrag

ord-3d1f1a8771074eb1ae80e3d456824fdf

Quelldatensatz

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08551984B2