反应详情

A solution of N-ethyldiisopropylamine (1.29 mL, 7.39 mmol) in DMF (15 mL) was added to a 50 mL round bottom flask charged with a mixture of methyl 3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenylcarbamimidothioate hydroiodide (1.16 g, 2.96 mmol, from preparation Q), 2-(4-fluorophenyl)pent-4-enoic acid (0.750 g, 3.25 mmol, from preparation AC), 1-hydroxybenzotriazole hydrate (0.905 g, 5.91 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.133 g, 5.91 mmol). The resulting mixture was magnetically stirred under nitrogen for 18 h at rt. Hydrazine (0372 mL, 11.84 mmol) was added to the reaction solution and the mixture was heated at 70° C. for 2 hr. The crude reaction mixture was poured into water (250 mL) and extracted with ethyl acetate (2×150 mL). The organic layer was washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford 5-(4-chloro-1-(4-fluorophenyl)butyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (1.02 g, 2.298 mmol, 78% yield). LC-MS (M+H)+ 443.3, ˜50% purity by UV integration. Used crude isolate in the next step without purification.

1. temperaturethe mixture was heated at 70° C. for 2 hr
2. customThe crude reaction mixture
3. extractionextracted with ethyl acetate (2×150 mL)
4. washThe organic layer was washed with brine (50 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo