Hydrochloric Acid → HCID 178523779, Verbindung

HRID 1161305Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1161305
C(O[C:6](=O)[NH:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=1[NH2:16])(C)(C)C.[CH:18]1(C=O)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.[Cl:26][C:27]1[CH:35]=[CH:34][C:30]([C:31](O)=O)=[CH:29][N:28]=1.C[O:37][C:38]([C@H:40]1[CH2:45][CH2:44][C@H:43]([N+:46]#[C-:47])[CH2:42][CH2:41]1)=[O:39].Cl.C[OH:50]>O1CCOCC1>[Cl:26][C:27]1[N:28]=[CH:29][C:30]([C:31]2[N:7]([CH:6]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[C:47]([NH:46][C@H:43]3[CH2:44][CH2:45][C@H:40]([C:38]([OH:37])=[O:39])[CH2:41][CH2:42]3)=[O:50])[C:8]3[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=3[N:16]=2)=[CH:34][CH:35]=1

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 887MethanolHCID 16275CyclohexanecarboxaldehydeHCID 792226-Chloronicotinic acidHCID 66619231tert-Butyl (2-amino-4,5-difluorophenyl)carbamateHCID 178484817HCID 178484817, Verbindung

Produkt 1

HCID 178523779HCID 178523779, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of (2-amino-4,5-difluoro-phenyl)-carbamic acid tert-butyl ester (0.2 g, 0.82 mmol) in methanol (4 mL) were added cyclohexanecarbaldehyde (0.16 mL, 1.22 mmol, 1.5 equiv.), 6-chloro-nicotinic acid (0.13 g, 0.82 mmol, 1.0 equiv.) and trans-4-Isocyano-cyclohexanecarboxylic acid methyl ester (0.137 mg, 0.82 mmol, 1.0 equiv.) and stirred at rt for 16 h. A solution of 4 M HCl in dioxane (4 mL) was added and the reaction mixture stirred at rt for 3 h. The solution was concentrated by evaporation under reduced pressure, the pH adjusted to 9 by addition of a solution of 1 M NaHCO3 and the aqueous layer extracted with ethyl acetate. The combined organic phases were dried over MgSO4 and concentrated by evaporation under reduced pressure. The crude material was dissolved in methanol (15 ml) and NaOH (5 ml) and DMF (1 ml) were added and the mixture heated to 50° C. overnight. The pH was adjusted to 4. A light brown solid appeared which was further purified by preparative HPLC. MS (ES+): 532 (M+H).

Aufarbeitung

  1. stirringthe reaction mixture stirred at rt for 3 h
  2. concentrationThe solution was concentrated by evaporation under reduced pressure
  3. additionthe pH adjusted to 9 by addition of a solution of 1 M NaHCO3
  4. extractionthe aqueous layer extracted with ethyl acetate
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated by evaporation under reduced pressure
  7. dissolutionThe crude material was dissolved in methanol (15 ml)
  8. additionNaOH (5 ml) and DMF (1 ml) were added
  9. temperaturethe mixture heated to 50° C. overnight
  10. customwas further purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-ae07cded5a2449e593fe12e0bcc14e47
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07816540B2

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