Water → 5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4(3H)-one

HRID 931336Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH3:16])[N:11]([NH:13][CH:14]=[NH:15])[CH:12]=1.[C:17](N1C=NC=N1)(N1C=NC=N1)=[O:18].O.C(OCC)(=O)C>O1CCCC1.CCCCCCC>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH3:16])[N:11]2[C:12]=1[C:17](=[O:18])[NH:15][CH:14]=[N:13]2

Participants

Conditions

Temperature: 55 °C

Procedure

Compound C4 (8.16 g, 37.4 mmol) in tetrahydrofuran (187 mL) was heated to 55° C., treated with 1,1′-carbonyldi(1,2,4-triazole) (7.36 g, 44.8 mmol) and stirred at 55° C. for 5 hours. The reaction was then cooled and stirred for an additional 3 days at room temperature. Removal of solvent in vacuo gave a solid, which was stirred with water (200 mL) for 1 hour and filtered to afford a pale brown powder. This was stirred in heptane (˜35 mL) and ethyl acetate (˜35 mL) for 24 hours and filtered, providing the product as an off-white powder (5.08 g). The aqueous filtrate was extracted once with ethyl acetate; this organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from heptane/ethyl acetate to provide additional product as a white powder. Total yield: 5.33 g, 21.8 mmol, 58%. LCMS m/z 245.0 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 7.73 (s, 1H), 7.62 (ddd, J=7.6, 7.3, 1.7 Hz, 1H), 7.40-7.46 (m, 1H), 7.24 (ddd, J=7.6, 7.6, 1.0 Hz, 1H), 7.18 (br dd, J=10, 8.5 Hz, 1H), 2.63 (s, 3H).

Workup

temperatureThe reaction was then cooled
stirringstirred for an additional 3 days at room temperature
customRemoval of solvent in vacuo
customgave a solid, which
filtrationfiltered
customto afford a pale brown powder
filtrationfiltered

Sources & evidence

ORD record: ord-bce04af747d04e9eb5cee506ac554948
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296761B2

Reaction notes

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