反应详情

温度

20 °C

To a solution of 4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide (156 mg, 0.389 mmol) in acetonitrile (4 mL) stirred in air at 20° C., was added 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (133 mg, 0.777 mmol). The reaction mixture was stirred at 20° C. for 1 hour, then 1-bromo-2-methylbutane (117 mg, 0.777 mmol) was added. The reaction then heated by microwaves to 150° C., for 30 minutes. After cooling the solvent was removed in vacuo and diluted with ethyl acetate. The organic phase was washed with water (5 mL), then dried using a hydrophobic frit. The solvent was removed in vacuo to give the crude product as an orange oil. Purification of the crude was attempted using flash silica (Si) chromatography (0-25% ethylacetate-cyclohexane gradient) followed by mass directed autoprep (ammonium carbonate modifier), however impurities still remained. A final purification using a silica (Si) cartridge (eluting with a gradient of 0-25% ethyl acetate-cyclohexane) provided a small amount of clean product (8.5 mg) as a colourless oil. LCMS (2 min, High pH) Rt 1.48 mins, m/z (ES+) 472 (M+H).

1. customThe reaction
2. temperaturethen heated by microwaves to 150° C., for 30 minutes
3. temperatureAfter cooling the solvent
4. customwas removed in vacuo
5. additiondiluted with ethyl acetate
6. washThe organic phase was washed with water (5 mL)
7. customdried
8. customThe solvent was removed in vacuo
9. customto give the crude product as an orange oil
10. customPurification of the crude
11. customA final purification
12. washeluting with a gradient of 0-25% ethyl acetate-cyclohexane)