Tetrahydrofuran → HCID 57932916, Verbindung

HRID 1432658Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1432658
C1COCC1.Br[C:7]1[N:11]([CH3:12])[N:10]=[CH:9][N:8]=1.[CH2:13]([CH:15]([C:18]1[C:19]2[N:20]([C:25]([C:29]3[S:30][C:31](I)=[CH:32][C:33]=3[O:34][CH3:35])=[C:26]([CH3:28])[N:27]=2)[N:21]=[C:22]([CH3:24])[CH:23]=1)[CH2:16][CH3:17])[CH3:14]>CCOC(C)=O.[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:13]([CH:15]([C:18]1[C:19]2[N:20]([C:25]([C:29]3[S:30][C:31]([C:7]4[N:11]([CH3:12])[N:10]=[CH:9][N:8]=4)=[CH:32][C:33]=3[O:34][CH3:35])=[C:26]([CH3:28])[N:27]=2)[N:21]=[C:22]([CH3:24])[CH:23]=1)[CH2:16][CH3:17])[CH3:14]

Komponenten

7

Edukt 3

HCID 8028Tetrahydrofuran2×HCID 1401211H-1,2,4-Triazole, 5-bromo-1-methyl-HCID 68839933HCID 68839933, Verbindung

Produkt 1

HCID 57932916HCID 57932916, VerbindungAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysator2×HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

To a slurry of 0.05 g/mL of Reike® Zn in THF (2.8 mL, 2.11 mmol) is added 5-bromo-1-methyl-1H-[1,2,4]triazole and THF (2 mL). The solution is heated at 65° C. for 1 hour, cooled to ambient temperature and the excess Zn allowed to settle for 1 hour. The solution is transferred to a flask containing 8-(1-ethyl-propyl)-3-(5-iodo-3-methoxy-thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.32 g, 0.70 mmol) and Pd(PPh3)4 (0.041 g, 0.035 mmol). The solution is heated at 65° C. overnight, diluted with EtOAc (30 mL) washed with sat. NH4Cl (30 mL). The aqueous phase is extracted with EtOAc (20 mL). The combined organic layers are dried over MgSO4, filtered and concentrated. The reside is purified by ISCO column chromatography (20%-65% EtOAc/hexane gradient) followed by ISCO column chromatography (100% Et2O) furnish the title compound (0.19 g, 0.46 mmol, 62%). 1H NMR (CDCl3) δ 0.86 (t, J=7.5 Hz, 6H), 1.73-1.91 (m, 4H), 2.51 (s, 3H), 2.52 (s, 3H), 3.26-3.37 (m, 1H), 3.92 (s, 3H), 4.15 (s, 3H), 6.67 (s, 1H), 7.48 (s, 1H), 7.89 (s, 1H). LC/MS (m/z): calcd. for C21H26N6OS (M+H)+: 411.5. found: 411.3.

Aufarbeitung

  1. temperaturecooled to ambient temperature
  2. customThe solution is transferred to a flask
  3. temperatureThe solution is heated at 65° C. overnight
  4. washwashed with sat. NH4Cl (30 mL)
  5. extractionThe aqueous phase is extracted with EtOAc (20 mL)
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe reside is purified by ISCO column chromatography (20%-65% EtOAc/hexane gradient)

Quellen und Nachweise

ORD-Eintrag
ord-804e14497b294914ab7b68e4149dd0d4
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612067B2

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