反应详情

A solution of 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 38A, 625.2 mg, 2.18 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (908.3 mg, 2.39 mmol), N,N-diisopropylethylamine (1.1 mL, 6.53 mmol), and 3-aminopyridazine (310.6 mg, 3.27 mmol) in dry N,N-dimethylformamide (11 mL) was stirred at 25° C. under nitrogen for 72 h. The reaction mixture was concentrated in vacuo to remove N,N-dimethylformamide. The resulting residue was diluted with ethyl acetate (200 mL). The organic layer was washed with a 10% aqueous hydrochloric acid solution and a saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-pyridazin-3-yl-propionamide (493.8 mg, 62%) as a white foam: mp 70–71° C.; EI-HRMS m/e calcd for C18H19Cl2N3O (M+) 363.0905, found 363.0908.

1. concentrationThe reaction mixture was concentrated in vacuo
2. customto remove N,N-dimethylformamide
3. additionThe resulting residue was diluted with ethyl acetate (200 mL)
4. washThe organic layer was washed with a 10% aqueous hydrochloric acid solution
5. dry with materialThe organic layer was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo