3,5-Dichlorobenzoyl chloride → 1-(3,5-dichlorobenzoyl)-5-fluoro-4-imino-3-methyl-3,4-dihydropyrimidin-2(1H)-one

HRID 918752Notes

Reaction equation

C[Si](O/C(=N/[Si](C)(C)C)/C)(C)C.[F:13][C:14]1[C:15](=[NH:22])[N:16]([CH3:21])[C:17](=[O:20])[NH:18][CH:19]=1.[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[C:31]([Cl:33])[CH:32]=1)[C:27](Cl)=[O:28]>C(#N)C>[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[C:31]([Cl:33])[CH:32]=1)[C:27]([N:18]1[CH:19]=[C:14]([F:13])[C:15](=[NH:22])[N:16]([CH3:21])[C:17]1=[O:20])=[O:28]

Participants

Conditions

Temperature: 70 °C

Procedure

In a capped vial, (E)-trimethylsilyl-N-(trimethylsilyl)acetimidate (157 mg, 0.774) was added to 5-fluoro-4-imino-3-methyl-3,4-dihydropyrimidin-2(1H)-one (100 mg, 0.704 mmol) and acetonitrile (1.0 mL) and heated at 70° C. for 30 min. The solution was cooled to room temperature and 3,5-dichlorobenzoyl chloride (133 mg, 0.633 mmol) was added dropwise and the contents were stirred overnight at room temperature. The reaction was concentrated with a stream of nitrogen. Diethyl ether (Et2O; 3 mL) was added and the vial was recapped and shaken briefly. The solids were filtered and washed with a small amount of Et2O and air dried to provide the title compound as a white solid (78 mg, 35%): mp 142-143° C.; 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J=5.5 Hz, 1H), 7.56 (t, J=1.8 Hz, 1H), 7.49 (d, J=1.8 Hz, 2H), 3.40 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 166.97, 136.71, 135.23, 135.12, 132.76, 132.37, 127.95, 126.48, 114.66, 114.27, 29.56, 29.01; ESIMS m/z 317 ([M+H]+).

Workup

temperatureThe solution was cooled to room temperature
concentrationThe reaction was concentrated with a stream of nitrogen
additionDiethyl ether (Et2O; 3 mL) was added
stirringshaken briefly
filtrationThe solids were filtered
washwashed with a small amount of Et2O and air
customdried

Sources & evidence

ORD record: ord-2c579260304d4b49981547856160e668
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09271497B2

Reaction notes

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