反应详情

Lithium hydroxide (56 mg, 1.3 mmol) was added to a solution of ethyl 2-(4-(tert-butoxycarbonyl)-2-((pyridin-3-yloxy)methyl)piperazin-1-yl)-4-methyloxazole-5-carboxylate (200 mg, 0.448 mmol) in THF (2 mL), MeOH (2 mL), and water (1 mL). After 3 h, 2.5 mL of the reaction mixture was removed and acidified to pH ˜3 with 1 N aqueous HCl. This was diluted with water (15 mL) and extracted with EtOAc (3×30 mL). The combined extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting yellow oil was dissolved in DMF (3 mL) and benzylamine (0.027 mL, 0.246 mmol), triethylamine (0.094 mL, 0.672 mmol) and TBTU (108 mg, 0.336 mmol) were added. After 14 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient). This gave the title compound as a brown solid. LC-MS: RT=7.79 min, [M+H]+=508.9.

1. custom2.5 mL of the reaction mixture was removed
2. additionThis was diluted with water (15 mL)
3. extractionextracted with EtOAc (3×30 mL)
4. dry with materialThe combined extracts were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. dissolutionThe resulting yellow oil was dissolved in DMF (3 mL)
8. waitAfter 14 h
9. concentrationthe reaction mixture was concentrated under reduced pressure
10. custompurified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient)