反应详情

温度

70 °C

A mixture of 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (0.072 g, 0.179 mmol, Example #35, Step H), KOH aqueous (50% w/v 0.118 g, 2.10 mmol) and 1,4-dioxane (0.1 mL) was heated to about 70° C. To the reaction mixture was added 3-(bromomethyl)-5-methylisoxazole (0.063 g, 0.359 mmol, Maybridge) and TBAB (0.004 g, 0.01 mmol) and the reaction mixture was stirred for about 24 h. To the reaction mixture was added 3-(bromomethyl)-5-methylisoxazole (0.063 g, 0.36 mmol, Maybridge) and aqueous KOH (50% w/v 0.118 g, 2.10 mmol) and stirring was continued for about 24 h. The reaction was cooled to ambient temperature and EtOAc (10 mL) and water (5 mL) were added. The layers were separated and the aqueous layer was extracted with EtOAc (10 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to give 3-(((1R,3R,4S)-3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)methyl)-5-methylisoxazole (0.064 g, 72%): LC/MS (Table 1, Method b) Rt=2.58 min; MS m/z: 497 (M+H)+.

1. stirringstirring
2. waitwas continued for about 24 h
3. temperatureThe reaction was cooled to ambient temperature
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with EtOAc (10 mL)
6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
7. filtrationfiltered
8. customThe crude material was purified by silica gel chromatography
9. washeluting with a gradient of 0-5% MeOH in DCM