Sodium Carbonate → Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylate

HRID 43836

Reaktionsgleichung

Reaktionsgleichung von HRID 43836
Cl.O1CCOCC1.[Cl:8][C:9]1[N:10]=[C:11]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=O)[CH2:21][C@H:20]2[F:32])=[O:17])[NH:12][C:13]=1[CH2:14][CH3:15].BrC1[S:35][C:36]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:37]([CH3:39])[N:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[Cl:8][C:9]1[N:10]=[C:11]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([C:25]3[S:35][C:36]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:37]([CH3:39])[N:38]=3)[CH2:21][C@H:20]2[F:32])=[O:17])[NH:12][C:13]=1[CH2:14][CH3:15]

Komponenten

6

Edukt 4

HCID 10340Sodium CarbonateHCID 2824057Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylateHCID 204431481,4-Dioxane hydrochlorideHCID 86648766tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidine-1-carboxylate

Produkt 1

HCID 86648767Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylateAusbeute 56,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A 4 N hydrochloric acid/1,4-dioxane solution (3 mL) was added to tert-butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidine-1-carboxylate obtained in Example (196b) (159 mg, 0.424 mmol) under ice-cooling, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure, and DMF (4 mL) was added. Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate (117 mg, 0.467 mmol) and sodium carbonate (225 mg, 2.12 mmol) were added, and the mixture was stirred at 90° C. for three hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and brine, and dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=1:1 v/v) to obtain 106 mg of the title compound (56%) as a colorless solid.

Aufarbeitung

  1. temperaturecooling
  2. concentrationThe reaction solution was concentrated under reduced pressure, and DMF (4 mL)
  3. additionwas added
  4. stirringthe mixture was stirred at 90° C. for three hours
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe resulting organic layer was washed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe insoluble matter was separated by filtration
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe resulting residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=1:1 v/v)

Quellen und Nachweise

ORD-Eintrag
ord-ca66e5bc74be42f2ba2c26a490cc382e
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536197B2

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