1,2-Dimethoxyethane → 5,7-Difluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

HRID 69210Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69210
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[C:13]([F:23])=[C:14]4[C:19](=[CH:20][C:21]=3[F:22])[N:18]=[CH:17][CH:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1.[O:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]1[O:30][CH2:31][CH2:32][N:33]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(C)=O>[F:23][C:13]1[C:12]([CH2:11][C:8]2[N:6]3[N:7]=[C:2]([C:36]4[CH:35]=[N:34][N:33]([CH2:32][CH2:31][O:30][CH:25]5[CH2:26][CH2:27][CH2:28][CH2:29][O:24]5)[CH:37]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[C:21]([F:22])[CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][CH:17]=[N:18]2

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 581475266-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-5,7-difluoro-quinolineHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Produkt 1

HCID 686342555,7-Difluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

6-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-5,7-difluoro-quinoline (Stage 171.2, 90 mg, 0.272 mmol) was introduced in a microwave reactor together with 1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 88 mg, 0.272 mmol), tetrakis-(triphenylphosphine)-palladium (15.72 mg), 2 M Na2CO3 (0.490 mL) and DME (0.9 mL). The mixture was heated at 150° C. under microwave irradiation for 30 min. The RM was taken up with EtOAc and washed with 10% Na2CO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in MeOH and filtered through a cartridge of PL-Thiol to remove the palladium. The filtrate was then purified by preparative HPLC with acetonitrile and water (+0.1% TFA) to afford the title compound (tR 1.1 min (conditions 2), MH+=491).

Aufarbeitung

  1. washwashed with 10% Na2CO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in MeOH
  6. filtrationfiltered through a cartridge of PL-Thiol
  7. customto remove the palladium
  8. customThe filtrate was then purified by preparative HPLC with acetonitrile and water (+0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-8408c0714f0d43c98a75e8d03c30f219
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822468B2

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