反应详情

Benzyl-2-[3-chloro-5-(3-[(dimethylamino)methyl]phenethylamino)-2-methyl-6-oxo-1(6H)-pyrazinyl]acetate (preparation 20) (137 mg, 0.29 mmol) was dissolved in methanol:water (10:2, 20 ml), treated with Pearlman's catalyst (10 mg) and stirred under a hydrogen atmosphere (60 psi, room temperature, 2.5 hr). The catalyst was removed by filtration, followed by evaporation of the solvent and azeotroping with CH2Cl2 to yield a crude yellow solid. To the crude mixture, 1H-indol-5-ylmethylamine (preparation 8) (43 mg, 0.29 mmol), HOBT (46 mg, 0.34 mmol), WSCDI.HCl (74 mg, 0.39 mmol), N-methylmorpholine (0.061 ml, 0.55 mmol) and DMF (5 ml) were stirred at room temperature for 18 hr. The resultant mixture was evaporated to dryness and azeotroped with CH2Cl2. Water (2 ml) was added followed by aq Na2CO3 (a few drops) and the residue treated with ethyl acetate and methanol. The organic layer was separated, dried over MgSO4. Filtration away from the drying agent followed by evaporation of the solvent gave the crude product which was purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 95:5 CH2Cl2:MeOH; 95:5:0.5 CH2Cl2:MeOH:NH3) to give the desired product (10 mg, 7%).

1. customThe catalyst was removed by filtration
2. customfollowed by evaporation of the solvent
3. customazeotroping with CH2Cl2
4. customto yield a crude yellow solid
5. customThe resultant mixture was evaporated to dryness
6. customazeotroped with CH2Cl2
7. additionWater (2 ml) was added
8. additionthe residue treated with ethyl acetate and methanol
9. customThe organic layer was separated
10. dry with materialdried over MgSO4
11. filtrationFiltration away from the drying agent
12. customfollowed by evaporation of the solvent
13. customgave the crude product which
14. customwas purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 95:5 CH2Cl2:MeOH; 95:5:0.5 CH2Cl2:MeOH:NH3)