反应详情

A mixture of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (1.0 g, 5.7 mmol) and chloroformic acid 4-nitrophenyl ester (1.14 g, 5.7 mmol) in CH2Cl2 (20 mL) was stirred at room temperature for 5 min under N2. To this mixture, Et3N (1.7 mL, 12.5 mmol) was added slowly and this generated mixture was added to a mixture of 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylic acid 4-methylbenzenesulfonate (2.4 g, 5.7 mmol, Step 12) in CH2Cl2 (15 mL) at rt. The resulting mixture was stirred at room temperature for 2 hrs. This mixture was washed with 0.5 N HCl aq (100 mL) and the organic layer was washed with saturated NaHCO3 aq (75 ml) then the organic layer was concentrated. The residue was diluted with EtOAc (75 mL) and it was concentrated until ca 15 mL. After seeding of the product, this mixture was stirred at room temperature for 30 min. During this procedure, the solid was formed and this mixture was filtered: Obtained solid was washed with EtOAc (10 mL), dried at 50° C. under vacuum to give 1.9 g (73%) of the titled compound as white solid.

1. stirringThe resulting mixture was stirred at room temperature for 2 hrs
2. washThis mixture was washed with 0.5 N HCl aq (100 mL)
3. washthe organic layer was washed with saturated NaHCO3 aq (75 ml)
4. concentrationthe organic layer was concentrated
5. additionThe residue was diluted with EtOAc (75 mL) and it
6. concentrationwas concentrated until ca 15 mL
7. stirringthis mixture was stirred at room temperature for 30 min
8. customDuring this procedure, the solid was formed
9. filtrationthis mixture was filtered
10. customObtained solid
11. washwas washed with EtOAc (10 mL)
12. customdried at 50° C. under vacuum