Reacción #44864

Ecuación de reacción

1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one

chloroformic acid 4-nitrophenyl ester

4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylic acid 4-methylbenzenesulfonate

Et3N

→

titled compound

Rendimiento 73.0%

4-{[4-({[(3-Isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl]amino}methyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-carboxylic acid

Rendimiento 73.0%

Disolventes

CH2Cl2

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 2 hrs
2. 2
   LavadoThis mixture was washed with 0.5 N HCl aq (100 mL)
3. 3
   Lavadothe organic layer was washed with saturated NaHCO3 aq (75 ml)
4. 4
   Concentraciónthe organic layer was concentrated
5. 5
   workup.ADDITIONThe residue was diluted with EtOAc (75 mL) and it
6. 6
   Concentraciónwas concentrated until ca 15 mL
7. 7
   workup.STIRRINGthis mixture was stirred at room temperature for 30 min
8. 8
   OtroDuring this procedure, the solid was formed
9. 9
   Filtraciónthis mixture was filtered
10. 10
    OtroObtained solid
11. 11
    Lavadowas washed with EtOAc (10 mL)
12. 12
    Otrodried at 50° C. under vacuum

Procedimiento

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 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.

Fuente