Dimethylformamide → HCID 57917438, compound

HRID 69207Notes

Reaction equation

HRID 69207 reaction equation
ClC1C=C[C:5]2[N:6]([C:8]([C:11]([C:13]3C=C4C(=CC=3)N=CC=C4)=O)=CN=2)[N:7]=1.Cl[C:24]1[CH:25]=[CH:26][C:27]2[N:28]([C:30]([C:33]([C:39]3[CH:40]=[C:41]4[C:46](=[CH:47][CH:48]=3)[N:45]=[CH:44][CH:43]=[CH:42]4)([OH:38])[C:34]([F:37])([F:36])[F:35])=[CH:31][N:32]=2)[N:29]=1.CN(C=O)C.FC([Si](C)(C)C)(F)F.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:35][C:34]([F:37])([F:36])[C:33]([C:30]1[N:28]2[N:29]=[C:24]([C:11]3[CH:13]=[N:7][N:6]([CH3:5])[CH:8]=3)[CH:25]=[CH:26][C:27]2=[N:32][CH:31]=1)([C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[N:45]=[CH:44][CH:43]=[CH:42]2)[OH:38]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 131731817HCID 131731817, compound

Product 1

HCID 57917438HCID 57917438, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-2,2,2-trifluoro-1-quinolin-6-yl-ethanol (6-chloro-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanone (Stage 1.2, 411 mg, 1.331 mmol) was dissolved in THF (1.5 mL) and DMF (1.5 mL) together with (trifluoromethyl)trimethylsilane (0.255 mL, 1.598 mmol) and the mixture was cooled down to 0° C. TBAF solution (1 M, 0.067 mL) was then added slowly. After 5 min, the RM was allowed to warm up to rt. After 24 h of stirring, it was warmed up to 50° C. and stirred for 24 h more. The reaction was then quenched with 1 N HCl. The precipitate formed was filtered off and identified as remaining pure starting material The solution was basified with pellets of NaOH. The second precipitate formed and filtered off was starting material as well. The aqueous layer was extracted twice with EtOAc and then the joined organics were washed with brine and dried over Na2SO4. After removing the solvent, the residue was purified by MPLC with DCM and MeOH to give the title compound as a brown solid (tR 0.8 min (conditions 2), MH+=379).

Workup

  1. temperatureit was warmed up to 50° C.
  2. stirringstirred for 24 h more
  3. customThe reaction was then quenched with 1 N HCl
  4. customThe precipitate formed
  5. filtrationwas filtered off
  6. customThe second precipitate formed
  7. filtrationfiltered off
  8. extractionThe aqueous layer was extracted twice with EtOAc
  9. washthe joined organics were washed with brine
  10. dry with materialdried over Na2SO4
  11. customAfter removing the solvent
  12. customthe residue was purified by MPLC with DCM and MeOH

Sources & evidence

ORD record
ord-5b18eecbd830486693541f67c1e1f94a
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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