反应详情

To a solution of 3-hydroxy-4-methoxy-pyridine-2-carboxylic acid acid (70 mg, 0.34 mmol) in 4 ml of acetonitrile triethylamine (0.13 mL, 0.96 mmol), 1-ethyl-3-dimethylaminopropyl)carbodiimide (77 mg, 0.41 mmol) and 1-hydroxy-7-azabenzotriazole (53 mg, 0.38 mmol) were added at RT. After stirring 15 min at RT, 1-[4-(4-amino-thiazol-2-yl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone (120 mg, 0.32 mmol) was added to the reaction mixture. After stirring 16 h at RT, the reaction mixture was diluted with 20 ml of ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution, 1 M hydrochloric acid and brine, dried over sodium sulfate and evaporated under reduced pressure. The remainder was purified by column chromatography on silica gel (ethylacetate/cyclohexane 1:1 to 8:2) to give 3-hydroxy-4-methoxy-pyridine-2-carboxylic acid (2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-amide (Compound No. 1.g.025) as a beige solid. 1H-NMR (400 MHz, CDCl3): δ=1.64-1.77 (m, 2H), 2.05-2.16 (m, 2H), 2.27 (s, 3H), 2.81-2.89 (m, 1H), 3.12-3.28 (m, 2H), 3.92 (s, 3H), 3.94-3.99 (m, 1H), 4.44-4.51 (m, 1H), 4.93 (d, 2H), 6.27 (s, 1H), 6.89 (d, 1H), 7.59 (s, 1H), 8.00 (d, 1H). MS: m/z=525 (M+1).

1. stirringAfter stirring 16 h at RT
2. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution, 1 M hydrochloric acid and brine
3. dry with materialdried over sodium sulfate
4. customevaporated under reduced pressure
5. customThe remainder was purified by column chromatography on silica gel (ethylacetate/cyclohexane 1:1 to 8:2)