反应详情

温度

80 °C

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole III-70a and III-70b were prepared in 2 steps according to the following procedures: 6-bromopyridin-3-ol (1.0 equiv) and sodium carbonate (10.0 equiv) are added to a microwave vial. Toluene, ethanol, and water (0.16 M, 2:2:1 v/v) are added followed by 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.5 equiv). The mixture is purged with argon for 15 min followed by the addition of palladium tetrakis (4 mol %). The reaction tube is then covered with aluminum foil and heated to 80° C. in an oil bath for 17 h. After cooling the reaction was transferred to a separatory funnel with excess water and ethyl acetate. The organic layer was then washed with water (1×), saturated ammonium chloride (1×) and brine (1×). The aqueous layers were combined and washed with ethyl acetate (1×). The organic layers were then combined, dried over sodium sulfate, concentrated and purified using flash silica gel chromatography (gradient methanol/methylene chloride) to provide 6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-ol III-69 as a white solid. This compound is then reacted with racemic 3-bromo-4,5-dihydroisoxazole III-66 using Method 5 to provide the desired racemic compound III-70. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=430.0 m/z. Activity: A

1. customThe mixture is purged with argon for 15 min
2. additionfollowed by the addition of palladium tetrakis (4 mol %)
3. temperatureAfter cooling the reaction
4. customwas transferred to a separatory funnel with excess water and ethyl acetate
5. washThe organic layer was then washed with water (1×), saturated ammonium chloride (1×) and brine (1×)
6. washwashed with ethyl acetate (1×)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated
9. custompurified