Trifluoroacetic acid → 5,7-Difluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

HRID 69260Notes

Reaction equation

HRID 69260 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[CH:21][C:22]4[N:23]([C:25]([CH2:28][C:29]5[C:30]([F:40])=[C:31]6[C:36](=[CH:37][C:38]=5[F:39])[N:35]=[CH:34][CH:33]=[CH:32]6)=[CH:26][N:27]=4)[N:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:40][C:30]1[C:29]([CH2:28][C:25]2[N:23]3[N:24]=[C:19]([C:17]4[CH:16]=[N:15][N:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)[CH:18]=4)[CH:20]=[CH:21][C:22]3=[N:27][CH:26]=2)=[C:38]([F:39])[CH:37]=[C:36]2[C:31]=1[CH:32]=[CH:33][CH:34]=[N:35]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 579173924-{4-[3-(5,7-Difluoro-quinolin-6-yl methyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 579174245,7-Difluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-{4-[3-(5,7-Difluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (Example 244, 219 mg, 0.401 mmol) was dissolved in DCM (3 mL) with TFA (0.619 mL, 8.03 mmol). The RM was stirred at rt for 1 h 15 min and it was quenched with ice water. It was extracted with EtOAc twice. The combined organic layers was washed with brine and dried over Na2SO4. It was filtered and the solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and the acetonitrile was removed. The aqueous solution was basified with 5% NaHCO3 solution and was extracted with EtOAc twice. Combined organic layers was washed with brine and dried over Na2SO4. It was filtered to afford after evaporation of the solvent the title compound as a white solid (tR 0.8 min (conditions 2), MH+=446).

Workup

  1. customit was quenched with ice water
  2. extractionIt was extracted with EtOAc twice
  3. washThe combined organic layers was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationIt was filtered
  6. customthe solvent was removed
  7. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  8. customthe acetonitrile was removed
  9. extractionwas extracted with EtOAc twice
  10. washCombined organic layers was washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationIt was filtered
  13. customto afford
  14. customafter evaporation of the solvent the title compound as a white solid (tR 0.8 min (conditions 2), MH+=446)

Sources & evidence

ORD record
ord-b007b7d312614a3b8b9f8d7259c08b88
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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