تفاعل #44864

معادلة التفاعل

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

المردود 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

المردود 73.0%

المذيبات

CH2Cl2

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 2 hrs
2. 2
   غسيلThis mixture was washed with 0.5 N HCl aq (100 mL)
3. 3
   غسيلthe organic layer was washed with saturated NaHCO3 aq (75 ml)
4. 4
   تركيزthe organic layer was concentrated
5. 5
   workup.ADDITIONThe residue was diluted with EtOAc (75 mL) and it
6. 6
   تركيزwas concentrated until ca 15 mL
7. 7
   workup.STIRRINGthis mixture was stirred at room temperature for 30 min
8. 8
   أخرىDuring this procedure, the solid was formed
9. 9
   ترشيحthis mixture was filtered
10. 10
    أخرىObtained solid
11. 11
    غسيلwas washed with EtOAc (10 mL)
12. 12
    أخرىdried at 50° C. under vacuum

الإجراء التجريبي

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.

المصدر