反应详情

(R)-2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine (50 mg, enantiomer B, preparation as described in WO2004085404) was dissolved in absolute dichloromethane (5 ml), and methyl 2-isocyanato-2-methylpropionate was added dropwise with stirring. After being stirred for 3 h and left to stand overnight, the mixture was admixed with water, the phases were separated and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The residue was purified by means of preparative HPLC. The fractions comprising product were purified, the acetonitrile was removed on a rotary evaporator, and the aqueous residue was neutralized with saturated potassium carbonate solution and extracted three times with ethyl acetate. After the combined ethyl acetate phases had been dried over magnesium sulfate, they were filtered and concentrated to dryness. The residue was dissolved in acetonitrile (1 ml) and admixed with 10% hydrochloric acid. After stirring for 2 h, the mixture was diluted with water (3 ml) and freeze-dried. 68 mg of the title compound were obtained.

1. stirringAfter being stirred for 3 h
2. waitleft
3. customthe phases were separated
4. extractionthe aqueous phase was extracted twice with dichloromethane
5. dry with materialThe combined organic phases were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by means of preparative HPLC
9. customwere purified
10. customthe acetonitrile was removed on a rotary evaporator
11. extractionextracted three times with ethyl acetate
12. dry with materialAfter the combined ethyl acetate phases had been dried over magnesium sulfate, they
13. filtrationwere filtered
14. concentrationconcentrated to dryness
15. dissolutionThe residue was dissolved in acetonitrile (1 ml)
16. stirringAfter stirring for 2 h
17. additionthe mixture was diluted with water (3 ml)
18. customfreeze-dried