Tetrahydrofuran → (6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanamine

HRID 2176527Notes

Reaction equation

HRID 2176527 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]([C:16]([CH2:19]O)=[CH:17][N:18]=3)[N:15]=2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].C([N:23](CC)CC)C.N([Na])=[N+]=[N-].CP(C)C.C1COCC1>C(Cl)Cl.O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]([C:16]([CH2:19][NH2:23])=[CH:17][N:18]=3)[N:15]=2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8]

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 68983TrimethylphosphineHCID 67502440(6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanolHCID 178514644HCID 178514644, compound2×

Product 1

HCID 68925952(6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanamine

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of (6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanol (0.442 g, 1.6 mmol) in CH2Cl2 (5 mL) was added Mesyl-Cl (0.37 ml, 4.7 mmol) and triethylamine (0.66 ml, 4.7 mmol)-slight exotherm, place flask in water bath- and the mixture stirred at rt 1 h. The mixture was concentrated in vacuo (without heating the flask) and the residue dissolved in DMF (2 mL) and azidosodium (0.23 g, 3.5 mmol) was added in one portion. After 45 minutes, additional azidosodium (0.40 g, 6.0 mmol) was added and the mixture stirred 1 h longer. The mixture was diluted with EtOAc, washed with water, brine, (back extract aq layer) and dry organic layer over Na2SO4, filter and evaporate. The azide intermediate was dissolved in THF (4 mL) and trimethylphosphine 1M in THF (2.4 ml, 2.4 mmol) was added. The reaction mixture was stir at rt until the bubbling stops, plus an additional 2 minutes, then water (1 mL) was added. The mixture was diluted with EtOAc, washed with NaHCO3 solution, sat. NaHCO3, (back extract aq layer), then dry organic layer over Na2SO4, filter and evaporate. The residue was purified via flash chromatography using al % NH4OH in MeOH in CH2Cl2 gradient to afford the title compound as a tan solid.

Workup

  1. concentrationThe mixture was concentrated in vacuo (
  2. temperaturewithout heating the flask) and the residue
  3. dissolutiondissolved in DMF (2 mL)
  4. waitAfter 45 minutes
  5. stirringthe mixture stirred 1 h longer
  6. washwashed with water, brine
  7. filtration(back extract aq layer) and dry organic layer over Na2SO4, filter
  8. customevaporate
  9. dissolutionThe azide intermediate was dissolved in THF (4 mL)
  10. stirringThe reaction mixture was stir at rt until the bubbling
  11. washwashed with NaHCO3 solution, sat. NaHCO3
  12. filtration(back extract aq layer), then dry organic layer over Na2SO4, filter
  13. customevaporate
  14. customThe residue was purified via flash chromatography

Sources & evidence

ORD record
ord-af163a213f394b8aaa2ea3645c3f4e76
Source dataset
uspto-grants-2015_06
Patent number
US09066954B2

Reaction notes

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