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

HRID 43749Notes

Reaction equation

HRID 43749 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18](OC(C)(C)C)=O)[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].Cl.C(OCC)(=O)C.C(N(CC)CC)C.BrC1[N:47]=[C:46]([C:48]([O:50][CH3:51])=[O:49])[CH:45]=[CH:44][CH:43]=1>CO.O>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:47]=[C:46]([C:48]([O:50][CH3:51])=[O:49])[CH:45]=[CH:44][CH:43]=3)[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 16217886Methyl 6-bromopyridine-2-carboxylateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86648452tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

Product 1

HCID 86648694Methyl cis(+/-)-6-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)pyridine-2-carboxylateYield 120.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

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.

Workup

  1. concentrationconcentration under reduced pressure
  2. dissolutionthe residue was dissolved in NMP (0.5 mL)
  3. stirringthe mixture was stirred
  4. customa microwave irradiation reactor at 150° C. for 10 minutes
  5. extractionfollowed by extraction with ethyl acetate
  6. additionSodium chloride was added to the aqueous layer
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentration under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=40/1, 20/1, 10/1)

Sources & evidence

ORD record
ord-5d0eaec761644774b427ea0d3fda83b0
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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