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

HRID 69264Notes

Reaction equation

HRID 69264 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH2:27][CH2:28][O:29]C4CCCCO4)[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1.Cl>C(Cl)Cl.O1CCOCC1>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH2:27][CH2:28][OH:29])[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 686334077-fluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

Product 1

HCID 579172972-{4-[3-(7-Fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 7-fluoro-6-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline (Stage 254.1, 72 mg, 0.152 mmol) in DCM (2 mL) stirred at rt was added a solution of HCl in dioxane (4 M, 0.381 mL). The RM was stirred 1 h at rt, during this time the product precipitated as an oil. The supernatant DCM was discarded, the residue was taken in EtOAc and washed with a solution of 10% NaHCO3. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/DCM/MeOH 19:1=100:0->0:100) to afford the title compound as a off white powder (tR 3.20 min (conditions 3), MH+=389.1, 1H-NMR in DMSO-d6: 8.82 (d, 1H), 8.42 (s, 1H); 8.33 (d, 2H); 8.12-8.05 (m, 2H); 8.02 (d, 1H); 7.76 (d, 1H); 7.58 (s, 1H); 7.52 (d, 1H); 7.49-7.43 (m, 1H); 4.97 (t, 1H); 4.54 (s, 2H); 4.18 (t, 2H); 3.72 (q, 2H)).

Workup

  1. customprecipitated as an oil
  2. washwashed with a solution of 10% NaHCO3
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/DCM/MeOH 19:1=100:0->0:100)

Sources & evidence

ORD record
ord-995a448021aa4214a85ddc2b76a065cc
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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