Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate → HCID 86648472, Verbindung

HRID 1424922Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1424922
[CH2:1]([Li])CCC.[Cl:6][C:7]1[N:8]=[C:9]([C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][N:20]([C:23]3[S:24][C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH:28]=O)[N:27]=3)[CH2:19][C@H:18]2[O:35][CH3:36])=[O:15])[NH:10][C:11]=1[CH2:12][CH3:13]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.[Cl-].[Na+].O>[Cl:6][C:7]1[N:8]=[C:9]([C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][N:20]([C:23]3[S:24][C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH:28]=[CH2:1])[N:27]=3)[CH2:19][C@H:18]2[O:35][CH3:36])=[O:15])[NH:10][C:11]=1[CH2:12][CH3:13]

Komponenten

6

Edukt 2

HCID 86648470Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 86648472HCID 86648472, VerbindungAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 74505Methyltriphenyliphosphonium bromideKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

Methyltriphenylphosphonium bromide (0.19 g, 0.53 mmol) was suspended in THF (4 mL), followed by cooling to −78° C. An n-butyllithium/1.58 M hexane solution (0.34 mL, 0.54 mmol) was added dropwise, followed by stirring for 25 minutes. Ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate obtained in Example (28a) (74 mg, 0.16 mmol) was added, and the mixture was heated to room temperature and stirred for one hour. Brine was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=4/1, 3/1, 1/1) to obtain 15 mg of the title compound as a pale yellow solid (21%).

Aufarbeitung

  1. temperaturethe mixture was heated to room temperature
  2. stirringstirred for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentration under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=4/1, 3/1, 1/1)

Quellen und Nachweise

ORD-Eintrag
ord-72393f5567944fdba13c67b1a1b13115
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08927588B2

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