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

HRID 43960

Reaktionsgleichung

Reaktionsgleichung von HRID 43960
Cl.[CH3:2][NH2:3].[Cl:4][C:5]1[N:6]=[C:7]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([C:21]3[S:22][C:23]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:24]([CH:26]=O)[N:25]=3)[CH2:17][C@H:16]2[O:33][CH2:34][CH3:35])=[O:13])[NH:8][C:9]=1[CH2:10][CH3:11].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.ClC(Cl)C.C(OCC)(=O)C>[Cl:4][C:5]1[N:6]=[C:7]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([C:21]3[S:22][C:23]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:24]([CH2:26][NH:3][CH3:2])[N:25]=3)[CH2:17][C@H:16]2[O:33][CH2:34][CH3:35])=[O:13])[NH:8][C:9]=1[CH2:10][CH3:11]

Komponenten

7

Edukt 3

HCID 5049666Sodium triacetoxyborohydrideHCID 6364545Methylamine hydrochlorideHCID 86648530ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate

Produkt 1

HCID 86648842Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-[(methylamino)methyl]-1,3-thiazole-5-carboxylateAusbeute 28,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 63651,1-DichloroethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

3 Å molecular sieves (500 mg) and methylamine hydrochloride (105 mg, 1.55 mmol) were added to a solution of ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate obtained in Example (28a) (500 mg, 1.03 mmol) in methanol (5 mL), and the mixture was stirred at room temperature for two hours. The reaction solution was filtered, and then the filtrate was concentrated under reduced pressure. Sodium triacetoxyborohydride (437 mg, 2.06 mmol) was added to a solution of the resulting residue in dichloroethane (10 mL), and the mixture was stirred at room temperature for 20.5 hours. The reaction solution was diluted with ethyl acetate, and then the mixture was extracted with a 1 N aqueous hydrochloric acid solution. A 1 N aqueous sodium hydroxide solution was added to the aqueous layer, followed by extraction with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate. Following filtration, the filtrate was concentrated under reduced pressure to obtain 145 mg of the title compound as a yellow oily substance (28%).

Aufarbeitung

  1. filtrationThe reaction solution was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. stirringthe mixture was stirred at room temperature for 20.5 hours
  4. extractionthe mixture was extracted with a 1 N aqueous hydrochloric acid solution
  5. additionA 1 N aqueous sodium hydroxide solution was added to the aqueous layer
  6. extractionfollowed by extraction with ethyl acetate
  7. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  8. filtrationfiltration
  9. concentrationthe filtrate was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-aba2839619da4b08afa5279e96268e42
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536197B2

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