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

HRID 43986Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 43986
[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]

Komponenten

5

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-89780092c0e949528a5ae96b44fc9cfd
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536197B2

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