1,1'-Carbonyldiimidazole → 3-(4-Amino-1,2,5-oxadiazol-3-yl)-4-(3-chloro-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one
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]([Cl:16])[CH:10]=2)=[N:4][O:5][N:6]=1.[C:19](N1C=CN=C1)(N1C=CN=C1)=[O:20]>O1CCCC1>[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]([Cl:16])[CH:10]=3)[C:19](=[O:20])[O:18][N:17]=2)=[N:4][O:5][N:6]=1Participants
Conditions
- Temperature
- 25 °C
Procedure
A solution of 4-amino-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide (80 g, 0.29 mol) [see US Pat. App. Pub. No. 2006/0258719] in tetrahydrofuran (500 mL) was treated with a solution of 1,1′-carbonyldiimidazole (53 g, 0.32 mol) in tetrahydrofuran (200 mL) and heated at reflux for 1 h. The reaction mixture was cooled to 25° C. and concentrated to the point where a large amount of solid precipitated. The heterogeneous mixture was diluted with ethyl acetate (1.5 L) and washed with 1 N HCl (2×300 mL), water (300 mL), and brine (200 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated to give the desired product (88 g, quantitative) as an off-white solid. This material was used without further purification. LCMS for C10H6ClFN5O3 (M+H)+: m/z=298.0. 1H NMR (400 MHz, DMSO-d6): δ 7.96 (dd, J=6.6, 2.3 Hz, 1H), 7.69-7.60 (m, 2H), 6.60 (s, 2H).
Workup
- temperatureheated
- temperatureat reflux for 1 h
- concentrationconcentrated to the point where a large amount of solid
- customprecipitated
- additionThe heterogeneous mixture was diluted with ethyl acetate (1.5 L)
- washwashed with 1 N HCl (2×300 mL), water (300 mL), and brine (200 mL)
- customThe organic layer was separated
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-07a192937c42413d8a9bbe13ad743d81
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08796319B2
Reaction notes
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