تفاعل #72027

معادلة التفاعل

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

المردود 120.9%

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

المردود 120.9%

المذيبات

Water

methanol

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر