反应详情

N-Cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide (Example 134, 0.172 g), potassium carbonate (0.114 g) and tert-butyl 4-(bromomethyl)piperidine-1-carboxylate (0.114 g) were stirred together in acetonitrile (10 mL) at reflux overnight. The cooled reaction mixture was evaporated to dryness and the residue partitioned between ethyl acetate (20 mL) and water (20 mL). The separated aqueous layer was further extracted into ethyl acetate (2×20 mL), the combined organics were dried (MgSO4) and evaporated. The residue was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (1 ml), after stirring at room temperature for 1 h, the solvent was evaporated to leave the crude product. Purification by preparative HPLC (Gemini column—acetonitrile/0.2% ammonia mobile phase) afforded the title compound as a solid (50 mg).

1. temperatureat reflux overnight
2. customThe cooled reaction mixture
3. customwas evaporated to dryness
4. customthe residue partitioned between ethyl acetate (20 mL) and water (20 mL)
5. extractionThe separated aqueous layer was further extracted into ethyl acetate (2×20 mL)
6. dry with materialthe combined organics were dried (MgSO4)
7. customevaporated
8. dissolutionThe residue was dissolved in dichloromethane (10 mL)
9. additiontreated with trifluoroacetic acid (1 ml)
10. customthe solvent was evaporated
11. customto leave the crude product
12. customPurification by preparative HPLC (Gemini column—acetonitrile/0.2% ammonia mobile phase)