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

HRID 69288Notes

Reaction equation

HRID 69288 reaction equation
[F:1][C:2]1[C:10]([CH2:11][C:12]2[N:16]3[N:17]=[C:18]([C:21]4[CH:22]=[N:23][N:24]([CH2:26][CH2:27][O:28]C5CCCCO5)[CH:25]=4)[CH:19]=[CH:20][C:15]3=[N:14][CH:13]=2)=[C:9]([F:35])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:36].Cl.C([O-])(O)=O.[Na+]>O1CCOCC1>[F:1][C:2]1[C:10]([CH2:11][C:12]2[N:16]3[N:17]=[C:18]([C:21]4[CH:22]=[N:23][N:24]([CH2:26][CH2:27][OH:28])[CH:25]=4)[CH:19]=[CH:20][C:15]3=[N:14][CH:13]=2)=[C:9]([F:35])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:36]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 686334013-(4,6-difluoro-1-methyl-1H-indazol-5-ylmethyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine

Product 1

HCID 579174392-{4-[3-(4,6-Difluoro-1-methyl-1H-indazol-5-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 3-(4,6-difluoro-1-methyl-1H-indazol-5-ylmethyl)-6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazine (Stage 285.1, 30 mg, 0.061 mmol) in dioxane (2 mL) stirred at 0° C. was added a solution of HCl in dioxane (4 M, 0.152 mL). The RM was stirred 1 h at rt, poured in a solution 10% NaHCO3, and the aqueous phase was extracted with DCM. The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, hexane/EtOAc=100:0->80:20) to afford the title compound as a white powder (tR 3.68 min (conditions 3), MH+=410.2, 1H-NMR in DMSO-d6: 8.38 (s, 1H); 8.19 (s, 1H); 8.06 (s, 1H); 8.04 (d, 1H); 7.53-7.46 (m, 3H); 4.97 (t, 1H); 4.40 (s, 2H); 4.18 (t, 2H); 3.97 (s, 3H); 3.76 (q, 2H)).

Workup

  1. extractionthe aqueous phase was extracted with DCM
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, hexane/EtOAc=100:0->80:20)

Sources & evidence

ORD record
ord-963ee83d76b84ab98a1e10dbab706db1
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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