3,5-Difluorobenzoyl chloride → 4-amino-1-(3,5-difluorobenzoyl)-5-fluoro-1H-pyrimidin-2-one

HRID 1260414Notes

Reaction equation

[NH2:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([OH:9])[N:3]=1.[F:10][C:11]1[CH:12]=[C:13]([CH:17]=[C:18]([F:20])[CH:19]=1)[C:14](Cl)=[O:15]>C(#N)C>[NH2:1][C:2]1[C:7]([F:8])=[CH:6][N:5]([C:14](=[O:15])[C:13]2[CH:12]=[C:11]([F:10])[CH:19]=[C:18]([F:20])[CH:17]=2)[C:4](=[O:9])[N:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To an 8 mL screw-cap vial containing 4-amino-5-fluoro-pyrimidin-2-ol* (100 mg, 0.775 mmol) and acetonitrile (CH3CN; 3 mL) was added bis-N,O-trimethylsilylacetamide (BSA; 378 microliters (μL), 1.55 mmol). The mixture was heated to 70° C. for 1 h resulting in a clear solution. After cooling to room temperature, 3,5-difluorobenzoyl chloride (182 μL, 1.55 mmol) was added, and the mixture was stirred at room temperature for 12 h. A white precipitate formed and was collected by vacuum filtration. The solid was washed with Et2O (1×10 mL) and air-dried overnight to yield the final product as a white solid (126 mg, 60%): mp 227-231° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.54 (br s, 1H), 8.27 (br s, 1H), 8.14 (d, J=6.8 Hz, 1H), 7.80-7.35 (m, 3H); ESIMS m/z 270 (M+H), 268 (M−H). *4-Amino-5-fluoro-pyrimidin-2-ol can be purchased commercially.

Workup

customTo an 8 mL screw-cap vial
customresulting in a clear solution
temperatureAfter cooling to room temperature
customA white precipitate formed
filtrationwas collected by vacuum filtration
washThe solid was washed with Et2O (1×10 mL)
customair-dried overnight

Sources & evidence

ORD record: ord-7eff41f78ccc4330b930fc23fe0f7147
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08470839B2

Reaction notes

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