Hydrochloric Acid → Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-(2,2-difluoroethoxy)piperidin-1-yl)-1,3-thiazole-5-carboxylate

HRID 43693

Reaktionsgleichung

Reaktionsgleichung von HRID 43693
[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](=O)C(F)(F)F)[CH2:14][C@H:13]2[O:24][CH2:25][CH:26]([F:28])[F:27])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].[OH-].[Li+].Cl.C(N(C(C)C)CC)(C)C.BrC1[S:43][C:44]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:45][N:46]=1>CO>[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[S:43][C:44]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:45][N:46]=3)[CH2:14][C@H:13]2[O:24][CH2:25][CH:26]([F:28])[F:27])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 3614103Ethyl 2-bromothiazole-5-carboxylateHCID 86648635cis(+/-)-4-Chloro-N-{3-(2,2-difluoroethoxy)-1-(trifluoroacetyl)piperidin-4-yl}-5-ethyl-1H-imidazole-2-carboxamide

Produkt 1

HCID 86648636Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-(2,2-difluoroethoxy)piperidin-1-yl)-1,3-thiazole-5-carboxylateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

cis(±)-4-Chloro-N-{3-(2,2-difluoroethoxy)-1-(trifluoroacetyl)piperidin-4-yl}-5-ethyl-1H-imidazole-2-carboxamide obtained in Example (121f) (144 mg, 0.33 mmol) was dissolved in methanol (4 mL). A 2 N aqueous lithium hydroxide solution (0.4 mL) was added, and the mixture was stirred at 40° C. for 40 minutes. The pH was adjusted to 4 by adding a 1 N aqueous hydrochloric acid solution, and the solvent was evaporated under reduced pressure. The residue was dissolved in DMA (5 mL). Diisopropylethylamine (130 mg, 1 mmol) and ethyl 2-bromo-1,3-thiazole-5-carboxylate (155 mg, 0.66 mmol) were added, and the mixture was stirred at 75° C. for one hour. Dilution with ethyl acetate, washing with water and brine, drying over anhydrous magnesium sulfate, and concentration under reduced pressure gave a residue, which was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 2/3, 3/2, 4/1) to obtain 0.12 g of the title compound as a colorless amorphous solid (74%).

Aufarbeitung

  1. customthe solvent was evaporated under reduced pressure
  2. dissolutionThe residue was dissolved in DMA (5 mL)
  3. stirringthe mixture was stirred at 75° C. for one hour
  4. washDilution with ethyl acetate, washing with water and brine
  5. dry with materialdrying over anhydrous magnesium sulfate, and concentration under reduced pressure
  6. customgave a residue, which
  7. customwas purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane=1/4, 2/3, 3/2, 4/1)

Quellen und Nachweise

ORD-Eintrag
ord-2e23c903b0874bc2bf82b88297c1c466
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536197B2

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