2-Butenoic acid, 3-(acetylamino)-, methyl ester, (2Z)- → 3-(2-fluoro-5-morpholinophenyl)-2,6-dimethylpyrimidin-4(3H)-one

To a solution of 2-fluoro-5-morpholinoaniline (0.35 g, 1.78 mmol) in CH2Cl2 (20 mL) was added trimethylaluminum (3.3 mL, 6.6 mmol, 2 M in toluene) dropwise. The reaction mixture was stirred at rt for 20 min, followed by the addition of a solution of methyl 3-acetaminocrotonate (0.30 g, 1.78 mmol) in anhydrous CH2Cl2 (10 mL). The reaction mixture was stirred at rt overnight, then quenched with saturated NH4Cl aqueous solution (80 mL) and extracted with CH2Cl2 (100 mL×3). The combined organic phases were washed with brine (150 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:2) to give the title compound as a yellow solid (0.37 g, 69%). The compound was characterized by the following spectroscopic data:

1. stirringThe reaction mixture was stirred at rt overnight
2. customquenched with saturated NH4Cl aqueous solution (80 mL)
3. extractionextracted with CH2Cl2 (100 mL×3)
4. washThe combined organic phases were washed with brine (150 mL)
5. dry with materialdried over anhydrous Na2SO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:2)

ORD record

ord-7b617234dd364153abdf4b6c3162e8a8

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434695B2