反应详情

A 50 mL round bottom flask was charged with 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (0.350 g, 1.16 mmol, Example #1, Step D), 8-ethyl-1,4-dioxaspiro[4.4]nonane-7-carboxylic acid (0.250 g, 1.25 mmol), and DCM (6.0 mL). To the reaction mixture was added HATU (0.483 g, 1.27 mmol) and TEA (0.64 mL, 4.6 mmol) and the resulting yellow suspension was stirred at rt for about 3 h. To the reaction solution was added DCM (25 mL) and the solution was washed with water and brine (20 mL each). The organic layer was dried over anhydrous MgSO4, filtered, and concd under reduced pressure to give a brown oil. The crude product was purified by flash silica gel chromatography (25 g Silicycle column) eluting with a gradient of: 0-10% MeOH in DCM over 25 min. The product containing fractions were concd under reduced pressure to give 8-ethyl-N′-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1,4-dioxaspiro[4.4]nonane-7-carbohydrazide as a foam (0.50 g, 89%): LC/MS (Table 1, Method c) Rt=1.49 min; MS m/z: 486 (M+H)+.

1. washthe solution was washed with water and brine (20 mL each)
2. dry with materialThe organic layer was dried over anhydrous MgSO4
3. filtrationfiltered
4. customconcd under reduced pressure to give a brown oil
5. customThe crude product was purified by flash silica gel chromatography (25 g Silicycle column)
6. washeluting with a gradient of: 0-10% MeOH in DCM over 25 min
7. additionThe product containing fractions