反应详情

温度

0 °C

The starting material ethyl pyrazole-4-carboxylate was saponified in analogy to Example 157, Step a), To a solution of the free acid (1 g, 5.86 mmol) in DMF (40 ml) were added DIPEA (4.10 ml, 23.46 mmol) and tert-butyl (5-(aminomethyl)-6-methylpyridin-2-yl)carbamate (1.531 g, 6.45 mmol). At 0° C., propylphosphonic anhydride (50% in DMF, 3.42 ml, 5.86 mmol) was added dropwise. Reaction mixture was stirred for 30 min at 0° C., then diluted with ethyl acetate and water. Phases were separated and organic layer was washed with NaHCO3 sat. solution and brine. Organic layer was dried over sodium sulfate, filtered and evaporated to afford the crude material, which was purified by silicagel chromatography (DCM/MeOH from 100/0 to 9/1 in 30 min) to afford the title compound. HPLC (Method G) Rt=1.209 min, MS (Method V) [M+H]+=332.3.

1. customReaction mixture
2. customPhases were separated
3. washorganic layer was washed with NaHCO3 sat. solution and brine
4. dry with materialOrganic layer was dried over sodium sulfate
5. filtrationfiltered
6. customevaporated
7. customto afford the crude material, which
8. customwas purified by silicagel chromatography (DCM/MeOH from 100/0 to 9/1 in 30 min)