反应详情

A 100-mL round-bottomed flask was charged with 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride (0.45 g, 1.13 mmol, Example 91), 10 mL of CH2Cl2, triethylamine (0.63 mL, 4.51 mmol), and 2-chloro-5-pyrimidinesulfonyl chloride (0.24 g, 1.13 mmol, Matrix Scientific, Columbia, S.C.). After stirring for 15 min at room temperature, the mixture was concentrated then diluted with 10 mL of EtOH and 10 mL of NH4OH. The mixture was stirred at room temperature for an additional 1 h and then diluted with EtOAc. The organics were separated, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography on silica gel (0 to 65% EtOAc in hexanes) to give 2-(4-(4-((2-amino-5-pyrimidinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.22 g). 1H NMR (400 MHz, CD3OD) δ=8.58 (s, 2H), 7.57 (d, J=8.8 Hz, 2H), 7.03 (d, J=9.2 Hz, 2H), 3.38-3.34 (m, 4H), 3.22-3.17 (m, 4H). m/z (ESI, +ve ion) 485.6 (M+H)+. GK-GKRP IC50 (Binding)=0.258 μM; GK-GKRP EC50 (LC MS/MS-2)=0.518 μM.

1. concentrationthe mixture was concentrated
2. additionthen diluted with 10 mL of EtOH and 10 mL of NH4OH
3. stirringThe mixture was stirred at room temperature for an additional 1 h
4. additiondiluted with EtOAc
5. customThe organics were separated
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by column chromatography on silica gel (0 to 65% EtOAc in hexanes)