1,1'-Carbonyldiimidazole → 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one

HRID 632525Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:7](=[N:17][OH:18])[NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[C:11]([Br:16])[CH:10]=2)=[N:4][O:5][N:6]=1.C1N=CN([C:24](N2C=NC=C2)=[O:25])C=1>C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:7]2[N:8]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[C:11]([Br:16])[CH:10]=3)[C:24](=[O:25])[O:18][N:17]=2)=[N:4][O:5][N:6]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 4-amino-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide (65.7 g, 208 mmol), N,N-carbonyldiimidazole (Sigma-Aldrich) (50.6 g, 312 mmol, 1.5 equiv.), and ethyl acetate (750 mL) was heated to 60° C. and stirred for 20 min. LCMS indicated reaction completed. The reaction was cooled to room temperature, washed with 1 N hydrochloric acid (2×750 mL), dried over sodium sulfate, and concentrated. The crude product was triturated with a mixture of dichloromethane, ethyl acetate, and diethyl ether to give the desired product (60.2 g, 85%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.05 (m, 1H), 7.69 (m, 1H), 7.57 (t, 1H, J=8.7 Hz), 6.58 (s, 2H); C10H5BrFN5O3 (MW 342.08), LCMS (EI) m/e 342/344 (M++H).

Workup

customreaction
temperatureThe reaction was cooled to room temperature
washwashed with 1 N hydrochloric acid (2×750 mL)
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe crude product was triturated with a mixture of dichloromethane, ethyl acetate, and diethyl ether

Sources & evidence

ORD record: ord-8500225cf76f4b0899bb6cc916d82d6c
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321755B2

Reaction notes

Loading…