反应详情

To a solution of methyl2-[(cyclopentylamino)methyl]-2-ethyl-butanoate (Intermediate 252; 7.1 g, 31.3 mmol) in acetone (150 mL) was added potassium carbonate (5.3 g, 38.0 mmol) followed by 2,4-dichloro-5-nitropyrimidine (Aldrich; 6.1 g, 31.3 mmol). The black mixture was stirred at room temperature for 18 hours. The reaction was filtered and the solvent removed in vacuo to yield a black gum, which was dissolved in acetic acid (175 mL) and iron (7.0 g, 125 mmol) added and the reaction heated at 80° C. overnight. The resulting solution was filtered and the solvent removed in vacuo, the black solid/gum was quenched with water (75 mL) and to this was added sodium carbonate until basic, the resultant black emulsion was filtered through a pad of celite. The obtained mixture was extracted with DCM (3×150 mL), dried and the solvent removed in vacuo to yield a black solid. This was passed through a bond elute column (50 g) eluting with 0-1% MeOH in DCM to afford a brown solid, which was triturated with diethyl ether to yield the title compound as a white solid (3.05 g, 30%)

1. filtrationThe reaction was filtered
2. customthe solvent removed in vacuo
3. customto yield a black gum, which
4. temperaturethe reaction heated at 80° C. overnight
5. filtrationThe resulting solution was filtered
6. customthe solvent removed in vacuo
7. customthe black solid/gum was quenched with water (75 mL)
8. additionto this was added sodium carbonate until basic, the resultant black emulsion
9. filtrationwas filtered through a pad of celite
10. extractionThe obtained mixture was extracted with DCM (3×150 mL)
11. customdried
12. customthe solvent removed in vacuo
13. customto yield a black solid
14. washelute column (50 g)
15. washeluting with 0-1% MeOH in DCM
16. customto afford a brown solid, which
17. customwas triturated with diethyl ether