Reacción #44879

Ecuación de reacción

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

chloroformic acid 4-nitrophenyl ester

1-{[4-(aminomethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid 4-methylbenzene sulfonate

1-{[4-(aminomethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid 4-methylbenzenesulfonate

Et3N

Et3N

→

titled compound

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

Disolventes

CH2Cl2

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGAfter stirring for 10 min
2. 2
   workup.STIRRINGthe resulting mixture was stirred at room temperature for 2 hr
3. 3
   LavadoThis mixture was washed with 0.5 N HCl aq (10 mL) and saturated NaHCO3 aq (10 mL)
4. 4
   Concentraciónthe organic layer was concentrated
5. 5
   workup.ADDITIONTo the residue, saturated NaHCO3 aq (15 mL) and heptane (15 mL) was added at room temperature
6. 6
   workup.STIRRINGit was stirred for 6 hrs at that temperature
7. 7
   Filtraciónthis mixture was filtered
8. 8
   LavadoThe obtained solid was washed with H2O and heptane
9. 9
   OtroAfter drying
10. 10
    Otrocrude material was obtained (1.0 g, 82%) as white solid
11. 11
    OtroThis crude material (4.0 g) was purified by recrystallization from toluene (36 mL)

Procedimiento

A mixture of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (486 mg, 2.8 mmol) and chloroformic acid 4-nitrophenyl ester (556 mg, 2.8 mmol) in CH2Cl2 (10 mL) was stirred at room temperature for 5 min. To this mixture, Et3N (0.84 mL, 6.1 mmol) was added slowly and this mixture became a solution. This solution was added to a mixture of 1-{[4-(aminomethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid 4-methylbenzene sulfonate (1.1 g, 2.8 mmol, Step 7) in CH2Cl2 (5 mL) at room temperature. After stirring for 10 min, Et3N (0.38 mL, 2.8 mmol) was added and the resulting mixture was stirred at room temperature for 2 hr. This mixture was washed with 0.5 N HCl aq (10 mL) and saturated NaHCO3 aq (10 mL) then the organic layer was concentrated. To the residue, saturated NaHCO3 aq (15 mL) and heptane (15 mL) was added at room temperature and it was stirred for 6 hrs at that temperature. Solid was observed and this mixture was filtered. The obtained solid was washed with H2O and heptane. After drying, crude material was obtained (1.0 g, 82%) as white solid. This crude material (4.0 g) was purified by recrystallization from toluene (36 mL) to give 2.6 g of the titled compound (66%) as white solid.

Fuente