Potassium Carbonate → (Rac)-7-fluoro-6-[1-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-quinoline

HRID 69267Notizen

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Reaktionsgleichung von HRID 69267
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=[N:11]1.Cl[C:25]1[CH:26]=[CH:27][C:28]2[N:29]([C:31]([CH:34]([C:36]3[CH:37]=[C:38]4[C:43](=[CH:44][C:45]=3[F:46])[N:42]=[CH:41][CH:40]=[CH:39]4)[CH3:35])=[CH:32][N:33]=2)[N:30]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:46][C:45]1[CH:44]=[C:43]2[C:38]([CH:39]=[CH:40][CH:41]=[N:42]2)=[CH:37][C:36]=1[CH:34]([C:31]1[N:29]2[N:30]=[C:25]([C:13]3[CH:12]=[N:11][N:10]([CH2:9][CH2:8][O:7][CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)[CH:14]=3)[CH:26]=[CH:27][C:28]2=[N:33][CH:32]=1)[CH3:35]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 581475216-(1-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)ethyl)-7-fluoroquinolineHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Produkt 1

HCID 68639506(Rac)-7-fluoro-6-[1-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-quinoline

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

To a solution of [2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 72.5 mg, 0.225 mmol), (rac)-6-[1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-7-fluoro-quinoline (Stage 255.2, 49 mg, 0.15 mmol), and 2 M K2CO3 (0.203 mL) in DME (1 mL) stirred at 80-90° C. under argon atmosphere was added PdCl2(PPh3)2 (3.2 mg). After 1.5 h and cooling to rt the RM was taken-up in DCM and water, the aqueous phase was extracted with DCM, the combined organic layers were dried over MgSO4, filtered, evaporated to dryness and the residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=100:0->80:20) to afford the title compound as a white solid (tR 4.14 min (conditions 3), MH+=487.2).

Aufarbeitung

  1. extractionwater, the aqueous phase was extracted with DCM
  2. dry with materialthe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customthe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=100:0->80:20)

Quellen und Nachweise

ORD-Eintrag
ord-43937494f7464dc38250a05605bbab51
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822468B2

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