Diisopropylethylamine → cis(+/-)-4-Chloro-5-ethyl-N-(1-formyl-3-methoxypiperidin-4-yl)-1H-imidazole-2-carboxylic acid amide

HRID 1425455Notes

Reaction equation

HRID 1425455 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:19])[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(C(C)C)CC)(C)C>CO>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([CH:18]=[O:19])[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 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 86648867cis(+/-)-4-Chloro-5-ethyl-N-(1-formyl-3-methoxypiperidin-4-yl)-1H-imidazole-2-carboxylic acid amideYield 27%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained in Example (1g) (30 mg, 0.08 mmol) was dissolved in methanol (0.5 mL). A 4 N hydrochloric acid/ethyl acetate solution (2.5 mL) was added, and the mixture was stirred at room temperature for 4.5 hours. Following concentration under reduced pressure, the residue was dissolved in DMF (2 mL). Diisopropylethylamine (0.054 mL, 0.31 mmol) was added, and the mixture was stirred at 140° C. using a microwave reactor for one hour. Saline was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. Following concentration under reduced pressure, the residue was purified by reverse phase high performance liquid chromatography (Develosil, 2 cm diameter×10 cm, 0.1% formic acid-containing acetonitrile/water mixed solvent) to obtain 6.6 mg of the title compound as a pale yellow solid (27%).

Workup

  1. concentrationconcentration under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (2 mL)
  3. stirringthe mixture was stirred at 140° C.
  4. customfor one hour
  5. additionSaline was added to the reaction solution
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentration under reduced pressure
  10. customthe residue was purified by reverse phase high performance liquid chromatography (Develosil, 2 cm diameter×10 cm, 0.1% formic acid-containing acetonitrile/water mixed solvent)

Sources & evidence

ORD record
ord-2e8c4c07c78d4707b0592618babe1702
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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