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

To a solution of 2-fluoro-N1-hexylbenzene-1,4-diamine (3.36 g, 16 mmol) in CH2Cl2 (20 mL) was added trimethylaluminium (40 mL, 80 mmol, 2 M in toluene) slowly. The mixture was stirred at rt for 0.5 h, followed by the addition of a solution of methyl 3-acetaminocrotonate (3.02 g, 19.2 mmol) in CH2Cl2 (5 mL). The reaction mixture was stirred at rt for 72 h, then quenched with saturated NH4Cl aqueous solution and extracted with CH2Cl2 (150 mL×3). The combined organic phases were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=4:1) to give the title compound as pale yellow oil (1.57 g, 31%). The compound was characterized by the following spectroscopic data:

1. stirringThe reaction mixture was stirred at rt for 72 h
2. customquenched with saturated NH4Cl aqueous solution
3. extractionextracted with CH2Cl2 (150 mL×3)
4. washThe combined organic phases were washed with brine
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)=4:1)

ORD record

ord-f3d7dec2d63d43b18c85bfa4f22ef3ad

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434695B2