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

HRID 69265Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69265
[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]([CH2:34][C:35]3[CH:36]=[C:37]4[C:42](=[CH:43][C:44]=3[F:45])[N:41]=[CH:40][CH:39]=[CH:38]4)=[CH:32][N:33]=2)[N:30]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.CCOC(C)=O.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:45][C:44]1[CH:43]=[C:42]2[C:37]([CH:38]=[CH:39][CH:40]=[N:41]2)=[CH:36][C:35]=1[CH2:34][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

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 581475166-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinolineHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Produkt 1

HCID 686334077-fluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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, 77 mg, 0.240 mmol), 6-(6-chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline (Stage 173.1, 55 mg, 0.160 mmol), PdCl2(PPh3)2 (5.6 mg) and 2 M K2CO3 (0.216 mL) in DME (0.5 mL was stirred at 90° C. for 2 h under argon atmosphere. The RM was then diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered, evaporated to dryness and the residue was purified (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/DCM/MeOH 9:1=100:0->0:100) to afford the title compound (tR 3.97 min (conditions 3), MH+=473.1).

Aufarbeitung

  1. washwashed with saturated aqueous NaHCO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customthe residue was purified (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/DCM/MeOH 9:1=100:0->0:100)

Quellen und Nachweise

ORD-Eintrag
ord-d37b436124ff4d93b244c3d02f068e6c
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822468B2

Notizen zur Reaktion

Wird geladen…