反应详情

温度

0 °C

A mixture of 4-[5-(2-chlorophenyl)-4-(4-{[2-(trimethylsilyl)-ethoxy]methyl}-4H-1,2,4-triazol-3-yl)-1,3-oxazol-2-yl]-5-methylpyridin-2-amine (0.12 g, 0.25 mmol) and TEA (0.087 mL, 0.62 mmol) in DCM (2 mL) was allowed to stir at 0° C. for 20 min. To this mixture was added cyclopropanecarbonyl chloride (0.056 mL, 0.62 mmol). The reaction mixture was allowed to stir at 0° C. for 2 h and then MeOH (20 mL) was added. The mixture was allowed to stir at rt for 20 min and was then concentrated. MeOH (25 mL) and aqueous saturated NaHCO3 (4 mL) were added to the residue and the mixture was allowed to stir at rt overnight before NaOH (1M, 3 mL) was added. The reaction mixture was allowed to stir rt for 3 h and then concentrated. EtOAc (30 mL) was added to the residue and the mixture was allowed to stir at rt for 30 min. The mixture was filtered and the filtrate was concentrated. DCM (5 mL) and TFA (2 mL) were added to the residue and the mixture was allowed to stir at rt overnight. The reaction mixture was concentrated and purified by column chromatography to give N-{4-[5-(2-chlorophenyl)-4-(4H-1,2,4-triazol-3-yl)-1,3-oxazol-2-yl]-5-methylpyridin-2-yl}cyclopropanecarboxamide (Compound I-77) (0.025 g, 24%). LCMS (AA): m/z=421 (M+H).

1. stirringto stir at 0° C. for 2 h
2. stirringto stir at rt for 20 min
3. concentrationwas then concentrated
4. additionMeOH (25 mL) and aqueous saturated NaHCO3 (4 mL) were added to the residue
5. stirringto stir at rt overnight before NaOH (1M, 3 mL)
6. additionwas added
7. stirringto stir rt for 3 h
8. concentrationconcentrated
9. additionEtOAc (30 mL) was added to the residue
10. stirringto stir at rt for 30 min
11. filtrationThe mixture was filtered
12. concentrationthe filtrate was concentrated
13. additionDCM (5 mL) and TFA (2 mL) were added to the residue
14. stirringto stir at rt overnight
15. concentrationThe reaction mixture was concentrated
16. custompurified by column chromatography