反应详情

100 mg (0.34 mmol) of 8-hydroxy-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]-pyridine-3-carboxamide, 246 mg (0.76 mmol) of caesium carbonate and 56 mg (0.38 mmol) of (bromomethyl)cyclobutane were added to 4.9 ml of dry DMF and the mixture was stirred for 60 min in an oil bath preheated to 60° C. After cooling, about 40 ml of water were added to the reaction mixture and the solution formed was extracted 3× with ethyl acetate. The combined organic phases were concentrated and the residue was purified by preparative HPLC (RP18 column, mobile phase: water/methanol gradient with addition of 0.1% TFA). All product-containing fractions were combined and concentrated. Saturated aqueous sodium bicarbonate solution was added to the residue, and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate, filtered, concentrated and dried under high vacuum. This gave 78 mg of the target compound (63% of theory, purity 100%).

1. custompreheated to 60° C
2. temperatureAfter cooling
3. customthe solution formed
4. extractionwas extracted 3× with ethyl acetate
5. concentrationThe combined organic phases were concentrated
6. customthe residue was purified by preparative HPLC (RP18 column, mobile phase: water/methanol gradient with addition of 0.1% TFA)
7. concentrationconcentrated
8. additionSaturated aqueous sodium bicarbonate solution was added to the residue
9. extractionthe mixture was extracted three times with ethyl acetate
10. dry with materialThe combined organic phases were dried over sodium sulphate
11. filtrationfiltered
12. concentrationconcentrated
13. customdried under high vacuum