N-Iodosuccinimide → 7-Cyclobutyl-5-iodo-3H-imidazo[5,1-f][1,2,4]triazin-4-one

HRID 2042277Notes

Reaction equation

[CH:1]1([C:5]2[N:13]3[C:8]([C:9](=[O:14])[NH:10][CH:11]=[N:12]3)=[CH:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1.[I:15]N1C(=O)CCC1=O>CN(C=O)C>[CH:1]1([C:5]2[N:13]3[C:8]([C:9](=[O:14])[NH:10][CH:11]=[N:12]3)=[C:7]([I:15])[N:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

Conditions

Temperature: 55 °C

Procedure

A solution of 7-cyclobutyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (789 mg, 4.15 mmol) and N-iodosuccinimide (NIS, 933 mg, 4.15 mmol) in anhydrous DMF (40 mL) was stirred overnight at rt. An additional 4 eq. of NIS was added and reaction was heated to 55° C. for 6 h. The reaction mixture was concentrated in vacuo and partitioned between DCM and H2O and separated. The aqueous layer was washed with DCM (3×) and the combined organic fractions were washed with 1M sodium thiosulfate (Na2S2O3) (1×), brine (1×), dried over sodium sulfate (Na2SO4), filtered, and concentrated in vacuo. The solid was triturated with 20% EtOAc in DCM and filtered through a fritted Buchner funnel resulting in the title compound as an off-white solid; 1H NMR (DMSO-d6, 400 MHz) δ 1.84-1.96 (m, 1H), 1.98-2.13 (m, 1H), 2.25-2.43 (m, 4H), 3.84-3.96 (m, 1H), 7.87 (s, 1H); MS (ES+): m/z 317.02 (100) [MH+], HPLC: tR=2.62 min (MicromassZQ, polar—5 min).

Workup

customreaction
concentrationThe reaction mixture was concentrated in vacuo
custompartitioned between DCM and H2O
customseparated
washThe aqueous layer was washed with DCM (3×)
washthe combined organic fractions were washed with 1M sodium thiosulfate (Na2S2O3) (1×), brine (1×)
dry with materialdried over sodium sulfate (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe solid was triturated with 20% EtOAc in DCM
filtrationfiltered through a fritted Buchner funnel

Sources & evidence

ORD record: ord-1329a3ca31ce4f8089865178d64dd780
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586546B2

Reaction notes

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