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Dimethylformamide → 5-(3-Isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-6-(2,4,5-trifluorophenyl)imidazo[2,1-b]oxazole

HRID 1930034
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1930034
I[C:2]1[N:9]2[C:5]([O:6][CH:7]=[CH:8]2)=[N:4][C:3]=1[C:10]1[CH:15]=[C:14]([F:16])[C:13]([F:17])=[CH:12][C:11]=1[F:18].C([Mg]Cl)(C)C.I[C:25]1[CH:26]=[CH:27][C:28]2[N:29]([C:31]([CH:34]([CH3:36])[CH3:35])=[N:32][N:33]=2)[N:30]=1.CN(C=O)C>C1COCC1.[Cl-].[Zn+2].[Cl-].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>[CH:34]([C:31]1[N:29]2[N:30]=[C:25]([C:2]3[N:9]4[C:5]([O:6][CH:7]=[CH:8]4)=[N:4][C:3]=3[C:10]3[CH:15]=[C:14]([F:16])[C:13]([F:17])=[CH:12][C:11]=3[F:18])[CH:26]=[CH:27][C:28]2=[N:33][N:32]=1)([CH3:36])[CH3:35]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 6228DimethylformamideHCID 579298865-Iodo-6-(2,4,5-trifluorophenyl)imidazo[2,1-b]oxazoleHCID 579298936-Iodo-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazineHCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 579299285-(3-Isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-6-(2,4,5-trifluorophenyl)imidazo[2,1-b]oxazoleAusbeute 3,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-65 °C

Versuchsvorschrift

A 50-mL round bottom flask was charged with 5-iodo-6-(2,4,5-trifluorophenyl)imidazo[2,1-b]oxazole (0.65 g, 1.8 mmol) and THF (4.5 mL) to give a white suspension. The mixture was cooled to about −65° C. followed by the addition of a 2.0 M solution of i-PrMgCl (1.1 mL, 2.1 mmol). The resulting suspension was stirred at about −55° C. for about 30 min and at about −30° C. for about 1.75 h. To the reaction mixture was added dropwise a prepared solution of zinc chloride (0.32 g, 2.3 mmol) in THF (3.0 mL) and the resulting suspension was stirred at about −30° C. for about 30 min. In a separate flask were mixed 6-iodo-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.49 g, 1.7 mmol, Preparation #H.1), Pd(PPh3)4 (Strem, 0.073 g, 0.071 mmol), and DMF (5.0 mL). This solution was added to the reaction flask, which was immediately heated to about 80° C. in order to solubilize the resulting mixture. The mixture was heated at about 80° C. for about 1 h. The cooled reaction mixture was concentrated to dryness under reduced pressure and the residue was dissolved in DCM and washed with 1 N HCl, 5 N HCl, water, and brine. The solution was dried over MgSO4, filtered, and concentrated to dryness under reduced pressure. The crude product was recrystallized from ACN to give a light yellow powder, followed by RP-HPLC (Table 1, Method l) purification to give the title compound as an off-white powder (0.025 g, 3.5%): LC/MS (Table 1, Method a) Rt=2.47 min; MS m/z 399.1 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 8.28 (d, 1 H), 8.26 (d, 1 H), 8.22 (d, 1 H), 7.85-7.71 (m, 2 H), 7.07 (dd, 1 H), 3.73-3.66 (m, 1 H), 1.44 (d, 6 H).

Aufarbeitung

  1. customto give a white suspension
  2. stirringthe resulting suspension was stirred at about −30° C. for about 30 min
  3. additionThis solution was added to the reaction flask, which
  4. temperaturewas immediately heated to about 80° C. in order
  5. temperatureThe mixture was heated at about 80° C. for about 1 h
  6. customThe cooled reaction mixture
  7. concentrationwas concentrated to dryness under reduced pressure
  8. dissolutionthe residue was dissolved in DCM
  9. washwashed with 1 N HCl, 5 N HCl, water, and brine
  10. dry with materialThe solution was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated to dryness under reduced pressure
  13. customThe crude product was recrystallized from ACN
  14. customto give a light yellow powder
  15. customfollowed by RP-HPLC (Table 1, Method l) purification

Quellen und Nachweise

ORD-Eintrag
ord-7fd8aa65a184497187efca5d9f8ed1eb
Quelldatensatz
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08188083B2

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