反应详情

温度

25 °C

A solution of 2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid (Intermediate 86, 1.93 g, 5.74 mmol) in N,N-dimethylformamide (26 mL, 0.22M) at 25° C. was treated with N,N-diisopropylethylamine (2.8 mL, 16.94 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (3.81 g, 8.61 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 4, 1.31 g, 6.64 mmol). The reaction was stirred at 25° C. over 2 nights. After this time, the reaction was diluted with ethyl acetate (150 mL) and was washed with a saturated aqueous ammonium chloride solution (150 mL), a saturated aqueous sodium bicarbonate solution (150 mL) and a saturated aqueous sodium chloride solution (150 mL), dried over magnesium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (AnaLogix 80 g, 25-75% gradient ethyl acetate/hexanes) afforded 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (1.52 g, 51%) as a light yellow solid as a mixture of diastereomers.

1. washwas washed with a saturated aqueous ammonium chloride solution (150 mL)
2. dry with materiala saturated aqueous sodium bicarbonate solution (150 mL) and a saturated aqueous sodium chloride solution (150 mL), dried over magnesium sulfate
3. filtrationfiltered
4. washrinsed
5. concentrationconcentrated in vacuo