Pyridine → HCID 11713257, Verbindung

HRID 1009202

Reaktionsgleichung

Reaktionsgleichung von HRID 1009202
C1C([N+]([O-])=O)=CC=C([Cl-][C:11]([O-])=[O:12])C=1.[F:14][C:15]([F:26])([F:25])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][OH:22])=[CH:19][CH:18]=1.N1C=CC=CC=1.[N+](C1C=CC(NC(=O)[O-])=CC=1)([O-])=O.Cl.[Cl:47][C:48]1[CH:49]=[C:50]([CH2:54][CH2:55][NH:56][C:57]([C:59]2[N:60]=[C:61]([CH2:64][NH2:65])[S:62][CH:63]=2)=[O:58])[CH:51]=[CH:52][CH:53]=1.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.[Cl-].[NH4+].CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl>[F:14][C:15]([F:25])([F:26])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][O:22][C:11](=[O:12])[NH:65][CH2:64][C:61]2[S:62][CH:63]=[C:59]([C:57](=[O:58])[NH:56][CH2:55][CH2:54][C:50]3[CH:51]=[CH:52][CH:53]=[C:48]([Cl:47])[CH:49]=3)[N:60]=2)=[CH:19][CH:18]=1

Komponenten

12

Edukt 5

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 1371844-(Trifluoromethoxy)benzenemethanolHCID 22371666HCID 22371666, VerbindungHCID 67304328HCID 67304328, Verbindung

Produkt 1

HCID 11713257HCID 11713257, VerbindungAusbeute 53,5 %

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

4-Nitrophenylchloroformate (0.1 g, 0.5 mmol) was added to a stirring solution of 4-(trifluoromethoxy)benzyl alcohol (0.09 g, 0.5 mmol), pyridine (0.07 mL, 0.9 mmol), and methylene chloride (2 mL). DMAP (6 mg) was added and the mixture was stirred for 12 hours. The mixture was diluted with saturated ammonium chloride and extracted 3× with methylene chloride. The combined organic layers were washed with 0.5 N NaHSO4 and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (EtOAc/hexane). The 4-nitrophenylcarbamate was mixed with 2-aminomethyl-thiazole-4-carboxylic acid [2-(3-chlorophenyl)ethyl]amide hydrochloride (0.14 g, 0.4 mmol) and DIEA (0.2 mL) in DMF (5 mL). The mixture was stirred for 12 hours. The mixture was diluted EtOAc and water. The layers were separated and the aqueous layer was extracted with 3×EtOAc. The combined organic layers were washed with 5% aqueous lithium chloride and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The material was purified by flash chromatography (EtOAc/hexane) to afford the title compound (0.11 g, 50%): 1H NMR (400 MHz, d6-DMSO): 8.42 (t, 1H), 8.30 (t, 1H), 8.11 (s, 1H), 7.48 (d, 2H), 7.36 (d, 2H), 7.27 (m, 3H), 7.17 (d, 1H), 5.11 (s, 2H), 4.49 (d, 2H), 3.48 (m, 2H), 2.84 (t, 2H); MS (ESI-LCMS) for C22H20ClF3N3O4S: 514 (MH+).

Aufarbeitung

  1. extractionextracted 3× with methylene chloride
  2. washThe combined organic layers were washed with 0.5 N NaHSO4 and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (EtOAc/hexane)
  7. stirringThe mixture was stirred for 12 hours
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with 3×EtOAc
  10. washThe combined organic layers were washed with 5% aqueous lithium chloride and brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe material was purified by flash chromatography (EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-7f824038613c45ef80381215ea8660b9
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07973061B2

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