反应详情

A solution of 0.22 g (0.5 mmol) of [6-amino-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 7) in 5 ml of acetone was treated with 0.35 ml=0.26 g (2.5 mmol) of Et3N, followed by 0.19 ml=0.21 g (2.0 mmol) of acetic anhydride and the reaction mixture was subsequently heated up to reflux. After 22 hours, it was poured into crashed ice, the pH was adjusted to 8-9 with sodium carbonate solution and it was extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 3:2) to give 0.12 g (51%) the N-[5-methyl-6-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-acetamide as light yellow solid [MS: 475.2 (MH+)] and 0.098 g (37%) of N-acetyl-N-[5-methyl-6-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-acetamide as yellow solid. MS: 517.2 (MH+).

1. temperaturethe reaction mixture was subsequently heated up
2. temperatureto reflux
3. additionit was poured
4. extractionwas extracted twice with EtOAc
5. washthe organic phases were washed with water
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customevaporated
9. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 3:2)