Hydrochloric Acid → 2-Amino-5-fluoro-4-hydroxy-1-methyl-6-oxo-1,6-dihydropyridine-carbonitrile

Combine dimethylfluoromalonate (10 g, 0.066 mol) and malononitrile (4.4 g, 0.066 mol) in THF (50 mL) and cool to about −35° C. Add DBU (20 mL, 0.128 mol) over about 20 minutes while keeping the internal temperature below about −25° C. When the addition of DBU is complete, slowly warm to ambient temperature. After 18 hours, slowly add aqueous methylamine (40%, 30 mL, 0.44 mol). After 2 hours, add aqueous sodium hydroxide (10 M, 1 mL). After 3 hours, evaporate in vacuo to obtain a largely aqueous residue, cool to about 0° C., add concentrated hydrochloric acid (about 5 mL) to a pH of about 1 to give a solid. Collect the solid by filtration and rinse with water and ethanol (10 mL) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ11.71 (s, 1H), 7.29 (s, 2H), 3.27 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ154.7 (d, J=21.9 Hz), 153.1, 151.4 (d, J=13.2 Hz), 129.5 (d, J=211 Hz), 115.4 (d, J=3.7 Hz), 63.2 (d, J=2.9 Hz), 28.7; 19F NMR (376 MHz, DMSO-d6) δ−178.9; MS (M+H)+m/z calcd 184.0. found 184.0.

1. customthe internal temperature below about −25° C
2. waitAfter 2 hours
3. waitAfter 3 hours
4. customevaporate in vacuo
5. customto obtain a largely aqueous residue
6. temperaturecool to about 0° C.
7. customto give a solid
8. customCollect the solid
9. filtrationby filtration
10. washrinse with water and ethanol (10 mL)

ORD record

ord-faa7e4ca89644b3e8c8ed6f980cfc2b0

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436200B2