Reaktion #72027

Reaktionsgleichung

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

Ausbeute 120.9%

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

Ausbeute 120.9%

Lösungsmittel

Water

methanol

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle