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

HRID 69218Notes

Reaction equation

HRID 69218 reaction equation
O1CCCCC1[O:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13]([C:15]2[CH:16]=[CH:17][C:18]3[N:19]([C:21]([CH:24]([C:26]4[CH:27]=[C:28]5[C:33](=[CH:34][CH:35]=4)[N:32]=[CH:31][CH:30]=[CH:29]5)[CH3:25])=[CH:22][N:23]=3)[N:20]=2)[CH:12]=[N:11]1.C(Cl)Cl.Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.O.CC#N>[N:32]1[C:33]2[C:28](=[CH:27][C:26]([CH:24]([C:21]3[N:19]4[N:20]=[C:15]([C:13]5[CH:12]=[N:11][N:10]([CH2:9][CH2:8][OH:7])[CH:14]=5)[CH:16]=[CH:17][C:18]4=[N:23][CH:22]=3)[CH3:25])=[CH:35][CH:34]=2)[CH:29]=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 68641062(Rac)-6-[1-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-quinoline

Product 1

HCID 57917405(Rac)-2-{4-[3-(1-quinolin-6-yl-ethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-ethanol

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

In a flask were introduced (rac)-6-[1-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-quinoline (Stage 177.1, 147 mg, 0.33 mmol) and DCM (4 mL), before adding dropwise HCl in dioxane (4 N, 0.248 mL). The RM was stirred at rt for 1 h and was then blown off with nitrogen. The residue was dissolved in water/CH3CN 1:1. The solution was basified with NaHCO3 (ca. 0.5 g) before being concentrated. The white suspension was filtered and the cake was washed with water, before being dried under vacuum. The crude was dissolved in MeOH/water and purified by preparative HPLC (H2O/CH3CN/TFA 1000:0:1 to 750:250:1 in 20 min.). Collected fractions containing the product were put together and basified with NaHCO3, before being concentrated. The resulting white suspension was filtered and the cake was washed with water, before being dried under high vacuum to give the title compound as a white solid (tR 1.83 min (conditions 8), MH+=360).

Workup

  1. concentrationbefore being concentrated
  2. filtrationThe white suspension was filtered
  3. washthe cake was washed with water
  4. custombefore being dried under vacuum
  5. dissolutionThe crude was dissolved in MeOH/water
  6. custompurified by preparative HPLC (H2O/CH3CN/TFA 1000:0:1 to 750:250:1 in 20 min.)
  7. additionCollected fractions containing the product
  8. concentrationbefore being concentrated
  9. filtrationThe resulting white suspension was filtered
  10. washthe cake was washed with water
  11. custombefore being dried under high vacuum

Sources & evidence

ORD record
ord-76b3502bdd7841f48fa2c9df3669a44b
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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