反应详情

温度

95 °C

TBTU (0.12 g), (S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (Example 14) (0.15 g) and methyl isonipecotate (0.041 g), followed by DIPEA (0.10 mL), were combined in 1% DMF-CH2Cl2 (10.1 mL) at room temperature and the solution was stirred for 1 h. The reaction was diluted with CH2Cl2, poured into 1N HCl, and extracted with CH2Cl2. The combined organic layers were washed with saturated aqueous NaHCO3 followed by H2O. The organic phase was dried (Na2SO4), filtered and concentrated. The resultant residue was re-dissolved in 30% HBr—AcOH and heated to 95° C. for 3 h. Following aqueous workup, the organic layer was dried (Na2SO4), filtered, concentrated, and the residue was purified by silica gel chromatography to afford the title compound (0.099 g) (738.2, M+1).

1. extractionextracted with CH2Cl2
2. washThe combined organic layers were washed with saturated aqueous NaHCO3
3. dry with materialThe organic phase was dried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe resultant residue was re-dissolved in 30% HBr—AcOH
7. dry with materialFollowing aqueous workup, the organic layer was dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customthe residue was purified by silica gel chromatography