Hydrochloric Acid → 2-{4-[3-(5,7-Difluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

HRID 69209Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69209
[F:1][C:2]1[C:11]([CH2:12][C:13]2[N:17]3[N:18]=[C:19]([C:22]4[CH:23]=[N:24][N:25]([CH2:27][CH2:28][O:29]C5CCCCO5)[CH:26]=4)[CH:20]=[CH:21][C:16]3=[N:15][CH:14]=2)=[C:10]([F:36])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.Cl>C(Cl)Cl.O1CCOCC1>[F:1][C:2]1[C:11]([CH2:12][C:13]2[N:17]3[N:18]=[C:19]([C:22]4[CH:23]=[N:24][N:25]([CH2:27][CH2:28][OH:29])[CH:26]=4)[CH:20]=[CH:21][C:16]3=[N:15][CH:14]=2)=[C:10]([F:36])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Komponenten

5

Edukt 2

HCID 313Hydrochloric AcidHCID 686342555,7-Difluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

Produkt 1

HCID 441867812-{4-[3-(5,7-Difluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

5,7-Difluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline (Stage 170.1, 82.2 mg, 0.168 mmol) was dissolved in DCM (2 mL) and a solution of 4 N HCl in dioxane (0.126 mL) was added. The RM was stirred at rt for 1 h and the solvent was removed. It was then taken up with EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over Na2SO4 and the solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The solvent was removed and the residue was diluted in MeOH. The solution was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt of the title compound (tR 0.8 min (conditions 2), MH+=407, 1H-NMR in DMSO-d6: 8.92 (dd, 1H); 8.51 (d, 1H); 8.38 (s, 1H); 8.06 (t, 2H); 7.72 (d, 1H); 7.59 (dd, 1H); 7.57 (s, 1H); 7.51 (d, 1H); 4.55 (s, 2H); 4.20 (t, 2H); 3.78-3.73 (m, 2H), 3.13 (s, 1H)).

Aufarbeitung

  1. customthe solvent was removed
  2. washwashed with saturated NaHCO3 and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customthe solvent was removed
  5. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  6. customThe solvent was removed
  7. additionthe residue was diluted in MeOH
  8. customto remove the TFA salt
  9. customThe filtrate was evaporated

Quellen und Nachweise

ORD-Eintrag
ord-794164ab7f4a40bf99c775229594d0ad
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822468B2

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