反应详情

A slurry of morpholine-3(S)-carboxylic acid (3.00 g, 22.9 mmol) in EtOH (115 ml) was stirred at RT. A solution of aqueous CH2O (3.42 ml, 45.8 mmol, 37% w/w in H2O) was added, followed by Pd(OH)2 (600 mg, 20% w/w on charcoal). The flask was charged with hydrogen (1 atm) and the grey slurry was stirred for 24 hr at RT under a balloon of hydrogen. The flask was purged with nitrogen and the black slurry was diluted with MeOH, filtered through filter paper and concentrated to a reduced volume. The pale grey solution was filtered through a 0.45 μm syringe filter to remove residual Pd(OH)2 and concentrated to yield a clear colorless oil. The oil was placed under high vacuum for 24 hr and a white, solid foam was isolated. The foam was dissolved in pyridine (200 ml) and 6-chloro-9H-β-carbolin-8-ylamine (3.74 g, 17.2 mmol) was added, followed by EDCI (5.87 g, 30.6 mmol). The clear pale orange solution was stirred at RT for 24 hr. The solution was diluted with H2O (300 ml) and poured into a separatory funnel containing EtOAc (300 ml). The mixture was shaken and the layers were separated. The aqueous layer was extracted with EtOAc (3×150 ml) and the combined organic layers were washed with H2O and brine. The organic layer was dried, filtered and concentrated to yield a brown oil which was placed under high vacuum. The resulting brown foam was triturated with MeOH and the precipitate which formed was filtered and washed with MeOH. The resulting pale yellow solid was purified via chiral HPLC to yield a white solid (3.23 g).

1. customThe flask was purged with nitrogen
2. additionthe black slurry was diluted with MeOH
3. filtrationfiltered
4. filtrationthrough filter paper
5. concentrationconcentrated to a reduced volume
6. filtrationThe pale grey solution was filtered through a 0.45 μm syringe
7. filtrationfilter
8. customto remove residual Pd(OH)2
9. concentrationconcentrated
10. customto yield a clear colorless oil
11. customa white, solid foam was isolated
12. additionpoured into a separatory funnel
13. stirringThe mixture was shaken
14. customthe layers were separated
15. extractionThe aqueous layer was extracted with EtOAc (3×150 ml)
16. washthe combined organic layers were washed with H2O and brine
17. customThe organic layer was dried
18. filtrationfiltered
19. concentrationconcentrated
20. customto yield a brown oil which
21. customThe resulting brown foam was triturated with MeOH
22. customthe precipitate which formed
23. filtrationwas filtered
24. washwashed with MeOH
25. customThe resulting pale yellow solid was purified via chiral HPLC