Reacción #44881

Ecuación de reacción

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

triethylamine

NaOH

1-(2-benzyloxycarbonyl-2-methylpropyl)-4-aminomethylpiperidine hydrochloride

tert-butyl [{1-(2-benzyloxycarbonyl-2-methylpropyl)piperidin-4-yl}methyl]carbamate

HCl

triethylamine

4-nitrophenyl chloroformate

→

title compound

Rendimiento 67.3%

N-({1-(2-benzyloxycarbonyl-2-methylpropyl)piperidin-4-yl}methyl)-3-isopropyl-2-oxo-2,3-dihydro-1 H-benzimidazole-1-carboxamide

Rendimiento 67.3%

Disolventes

dichloromethane

MeOH

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONTo the mixture was added
2. 2
   workup.STIRRINGThe resulting mixture was stirred for 13 h at room temperature
3. 3
   ExtracciónThe mixture was extracted with dichloromethane
4. 4
   LavadoThe extracts were washed with 0.5 M NaOH aq. and brine
5. 5
   Secadodried over MgSO4
6. 6
   Concentraciónconcentrated in vacuo
7. 7
   OtroThe residue was purified by preparative thin layer chromatography (silica gel, eluting with dichloromethane /methanol (10:1))

Procedimiento

To a stirred mixture of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (J. Med. Chem. 1999, 42, 2870-2880) (411 mg, 2.33 mmol) and triethylamine (1.00 mL, 7.17 mmol) in dichloromethane (20.0 mL) was added 4-nitrophenyl chloroformate (470 mg, 2.33 mmol) at room temperature. The resulting mixture was stirred for 2 h at room temperature. To the mixture was added a suspension of 1-(2-benzyloxycarbonyl-2-methylpropyl)-4-aminomethylpiperidine hydrochloride [prepared from concentration of a mixture of tert-butyl [{1-(2-benzyloxycarbonyl-2-methylpropyl)piperidin-4-yl}methyl]carbamate (step 1 of Example 1) (640 mg, 1.49 mmol) and 10% HCl in MeOH (20.0 mL)] and triethylamine (1.00 mL, 7.17 mmol) in dichloromethane (5.00 mL). The resulting mixture was stirred for 13 h at room temperature and 0.5 M NaOH aq. was added to the mixture. The mixture was extracted with dichloromethane. The extracts were washed with 0.5 M NaOH aq. and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by preparative thin layer chromatography (silica gel, eluting with dichloromethane /methanol (10:1)) to give 508 mg (63%) of the title compound as a pale yellow oil.

Fuente