반응 #156956

반응 방정식

4-amino-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide

1,1′-carbonyldiimidazole

→

desired product

수율 102.0%

3-(4-Amino-1,2,5-oxadiazol-3-yl)-4-(3-chloro-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one

수율 102.0%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   온도heated
2. 2
   온도at reflux for 1 h
3. 3
   농축concentrated to the point where a large amount of solid
4. 4
   기타precipitated
5. 5
   workup.ADDITIONThe heterogeneous mixture was diluted with ethyl acetate (1.5 L)
6. 6
   세척washed with 1N HCl (2×300 mL), water (300 mL), and brine (200 mL)
7. 7
   기타The organic layer was separated
8. 8
   건조dried over anhydrous sodium sulfate
9. 9
   여과filtered
10. 10
    농축concentrated

실험 절차

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 1N 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, 1 H), 7.69-7.60 (m, 2 H), 6.60 (s, 2 H).

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