反应详情

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 78d, 1.0 g, 3.33 mmol) dry DMF (15 ml) were added TBTU (1.12 g, 3.5 mmol) and triethylamine (675 mg, 929 μl, 6.67 mmol). The reaction mixture was stirred at room temperature for 30 minutes followed by addition of 2-amino-2-cyclopropylpropanenitrile (CAN 37024-73-0, 404 mg, 3.67 mmol). The reaction was stirred at room temperature for 18 hours. The reaction mixture was poured into a separatory funnel, diluted with ethylacetate and extracted with an 1.0M aqueous solution of sodium bicarbonate. The organic phase was collected and the aqueous phase was back-extracted with ethylacetate. The organic phases were combined, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting a heptane/ethylacetate gradient to yield the title compound (910 mg, 70%) as a light yellow oil. MS (ESI, m/z): 392.3 (M+H+).

1. stirringThe reaction was stirred at room temperature for 18 hours
2. additionThe reaction mixture was poured into a separatory funnel
3. extractionextracted with an 1.0M aqueous solution of sodium bicarbonate
4. customThe organic phase was collected
5. extractionthe aqueous phase was back-extracted with ethylacetate
6. dry with materialdried over sodium sulfate
7. customevaporated down to dryness
8. customThe crude material was purified by flash chromatography on silica eluting a heptane/ethylacetate gradient