反应详情

温度

0 °C

To a solution of 2-(ethyl-methyl-amino)-6-methyl-isonicotinic acid (2.03 g, 8.80 mmol) and DIPEA (3.41 g, 26.4 mmol) in DMF (80 mL) is added PyBOP (5.00 g, 9.61 mmol) at 0° C. The mixture is stirred for 15 min before 0.5 M NH3 in dioxane (52 mL) is added. Stirring is continued at rt for 2 h before the mixture is again cooled to 0° C. Pyridine (4.35 g, 44.8 mmol) followed by trifluoroacetic anhydride (9.29 g, 44.2 mmol) is carefully added and the reaction mixture is stirred for 2 h while warming to rt. The mixture is then stirred at 70° C. for 15 h, cooled to rt, diluted with DCM and washed with 10% aq. citric acid solution followed by sat. aq. Na2CO3-solution. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-(ethyl-methyl-amino)-6-methyl-isonicotinonitrile (257 mg) as a pale yellow oil; LC-MS: tR=0.58 min, [M+1]+=176.09.

1. additionis added
2. additionis carefully added
3. stirringthe reaction mixture is stirred for 2 h
4. temperaturewhile warming to rt
5. stirringThe mixture is then stirred at 70° C. for 15 h
6. temperaturecooled to rt
7. washwashed with 10% aq. citric acid solution
8. extractionextract
9. dry with materialis dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1