反应详情

温度

50 °C

tert-Butyl {2-[2-({3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}carbamate (from Step 1; 0.74 g, 1.7 mmol) was suspended in 2 M HOAc (5 mL) and acetonitrile (1 mL) and heated at 50° C. for two days. The solution was neutralized with concentrated aqueous ammonia. Brine was added (3 mL) and the mixture was extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4) and the solvent was removed under reduced pressure. The remaining oil was dissolved in dry DMSO (10 mL), potassium tert-butoxide (0.36 g, 3.2 mmol) was added followed by tert-butyl (3R)-4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate (from Example 5; 0.59 g, 1.9 mmol) and the mixture was heated at 50° C. for 20 minutes. The reaction mixture was diluted with water/brine (90:10) and extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4), the solvent was removed under reduced pressure and the remaining oil was chromatographed on a column of silica with hexane/EtOAc (70:30) as eluent to give 0.43 g (40%) of the title compound as a colorless oil. LC-UV purity: system (A) 100%. HRMS m/z calcd for C30H46N6O8 (M)+ 618.3377. found 618.3381. Step 3: {2-[2-({3-[2-({3-[(2R)-2-Methylpiperazin-1-yl]pyrazin-2-yl}oxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}amine, bis(trifluoroacetate).

1. extractionthe mixture was extracted with CHCl3 (×3)
2. dry with materialThe combined organic phases were dried (MgSO4)
3. customthe solvent was removed under reduced pressure
4. dissolutionThe remaining oil was dissolved in dry DMSO (10 mL)
5. extractionextracted with CHCl3 (×3)
6. dry with materialThe combined organic phases were dried (MgSO4)
7. customthe solvent was removed under reduced pressure
8. customthe remaining oil was chromatographed on a column of silica with hexane/EtOAc (70:30) as eluent