Reaction #72027

Reaction equation

Example ( 1g )

tert-Butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

hydrochloric acid ethyl acetate

Triethylamine

methyl 6-bromo-pyridine-2-carboxylate

→

title compound

Yield 120.9%

Methyl cis(±)-6-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)pyridine-2-carboxylate

Yield 120.9%

Solvents

Water

methanol

Conditions

Workup

1. 1
   Concentrationconcentration under reduced pressure
2. 2
   workup.DISSOLUTIONthe residue was dissolved in NMP (0.5 mL)
3. 3
   workup.STIRRINGthe mixture was stirred
4. 4
   Othera microwave irradiation reactor at 150° C. for 10 minutes
5. 5
   Extractionfollowed by extraction with ethyl acetate
6. 6
   workup.ADDITIONSodium chloride was added to the aqueous layer
7. 7
   Dryingdried over anhydrous sodium sulfate
8. 8
   Concentrationconcentration under reduced pressure
9. 9
   Otherthe residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=40/1, 20/1, 10/1)

Procedure

tert-Butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained by the method described in Example (1g) (25 mg, 0.06 mmol) was dissolved in methanol (3 mL). A 4 N hydrochloric acid/ethyl acetate solution (2 mL) was added, and the mixture was stirred at room temperature for one hour. Following concentration under reduced pressure, the residue was dissolved in NMP (0.5 mL). Triethylamine (9.81 mg, 0.1 mmol) and methyl 6-bromo-pyridine-2-carboxylate (13.96 mg, 0.06 mmol) were added, and the mixture was stirred using a microwave irradiation reactor at 150° C. for 10 minutes. Water was added to the reaction solution, followed by extraction with ethyl acetate. Sodium chloride was added to the aqueous layer, followed by reextraction with ethyl acetate four times. The organic layers were combined and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=40/1, 20/1, 10/1) to obtain 30.6 mg of the title compound.

Source