反应详情

A 100 mL round-bottom flask charged with 6-(4-fluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole (0.35 g, 1.1 mmol; prepared from A using 6-(4-fluorophenyl)-imidazo[2,1-b]oxazole [WO2004110990A2, Example 1, Steps 1-3], and NIS, C using 6-fluoropyridin-3-ylboronic acid [Asymchem], and D using 1M hydrazine in THF) in THF (10 mL) and DCM (10 mL) was treated with TEA (0.17 mL, 1.2 mmol) and 2-chlorobenzoyl chloride (0.14 mL, 1.1 mmol). The reaction mixture was stirred at ambient temperature for about 30 min. The reaction mixture was then washed with water, dried over MgSO4, filtered, and evaporated under reduced pressure to give 2-chloro-N′-(5-(6-(4-fluorophenyl)imidazo[2,1-b]oxazol-5-yl)pyridin-2-yl)benzohydrazide (0.50 g, 1.1 mmol, 89%). The crude material was dissolved in 1,4-dioxane (10 mL) and treated with thionyl chloride (0.2 mL, 2.8 mmol). After about 30 min at about 100° C., the reaction mixture was cooled to about 0° C. and the precipitate was collected by filtration and washed with DCM (5 mL). The solid was dissolved in EtOAc/MeOH and washed twice with water. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The mixture was purified by column chromatography using EtOAc then EtOAc/MeOH (98:2) as eluent and dried in a vacuum oven at about 50° C. to give the title compound as a tan solid (0.13 g, 27%): LC/MS (Table 1, Method a) Rt, =2.38 min; MS m/z: 430.1 (M+H)+.

1. washThe reaction mixture was then washed with water
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. customevaporated under reduced pressure