Acetonitrile → 4-amino-5-fluoro-N-methyl-2-oxo-N-phenylpyrimidine-1(2H)-carbothioamide

Temperature

65 °C

A 25 mL screw-top vial was charged with 4-amino-5-fluoropyrimidin-2-ol (100.1 mg, 0.775 mmol), CH3CN (3 mL) and BSA (0.284 mL, 1.162 mmol). The resulting mixture was then agitated on a rotary shaker at 65° C. for 90 min. After cooling to room temperature, methyl(phenyl)carbamothioic chloride (157.6 mg, 0.849 mmol) was added, and the reaction mixture was agitated on a rotary shaker at 65° C. for 16 h. After cooling to room temperature, the reaction mixture was diluted with CH2Cl2 (100 mL) and washed with satd aq NaCl solution (50 mL×2). The organic layer was then dried over Na2SO4, filtered, and concentrated in vacuo to afford a green oil. This crude material was then purified by normal phase chromatography (gradient, 0 to 35% MeOH/CH2Cl2) to provide 4-amino-5-fluoro-N-methyl-2-oxo-N-phenylpyrimidine-1(2H)-carbothioamide (80.1 mg, 37%) as a 90% pure beige/green solid: mp 192-196° C.; 1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J=6.7 Hz, 1H), 7.83 (s, 1H), 7.66 (s, 1H), 7.38 (m, 2H), 7.34-7.26 (m, 3H), 3.71 (s, 3H); ESIMS m/z 279 ([M+H]+).

1. temperatureAfter cooling to room temperature
2. stirringthe reaction mixture was agitated on a rotary shaker at 65° C. for 16 h
3. temperatureAfter cooling to room temperature
4. washwashed with satd aq NaCl solution (50 mL×2)
5. dry with materialThe organic layer was then dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto afford a green oil
9. customThis crude material was then purified by normal phase chromatography (gradient, 0 to 35% MeOH/CH2Cl2)

ORD record

ord-7b45416790d54dada1ec56ac9e9560cf

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552020B2