反应详情

To a solution of (1-((6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)methyl)-cyclobutyl)methanamine (0.225 g, 0.548 mmol) (prepared using A from Example #1, Step D, 2-(1-(tert-butoxycarbonylamino)cyclobutyl)acetic acid [prepared as described WO9921824A1], EDC•HCl, B with TEA, E with 4.0 M HCl in 1,4-dioxane) in DMF (10 mL) was added cyanoacetic acid (0.070 g, 0.822 mmol), HOBt (0.101 g, 0.658 mmol), EDC•HCl (0.126 g, 0.658 mmol) and DIEA (0.190 mL, 1.096 mmol) to give a brown solution. The mixture was stirred at ambient temperature for about 18 h. Water (20 mL) was added and the mixture was extracted with EtOAc (3×25 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concd in vacuo. The crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM to give N-((1-((6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)methyl)cyclobutyl)methyl)-2-cyanoacetamide as an off-white solid (0.030 g, 17%): LC/MS (Table 1, Method a) Rt=1.48 min; MS m/z: 324 (M+H)+.

1. customto give a brown solution
2. extractionthe mixture was extracted with EtOAc (3×25 mL)
3. dry with materialThe combined organic layers were dried over anhydrous MgSO4
4. filtrationfiltered
5. customThe crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM