Methyl morpholine oxide → 3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine-6-carbaldehyde

HRID 456176Notes

Reaction equation

HRID 456176 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([CH:22]=C)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1.C[N+]1([O-])CC[O:28]CC1.I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([CH:22]=[O:28])[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1

Participants

6

Reactant 3

HCID 82029Methyl morpholine oxideHCID 23667635Sodium periodateHCID 669271833-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)-6-vinylimidazo[1,2-b]pyridazine

Product 1

HCID 866660873-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine-6-carbaldehydeYield 39.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
46 °C

Procedure

To a mixture of 3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)-6-vinylimidazo[1,2-b]pyridazine (50 mg, 0.163 mmol) osmium(VIII) oxide (103 mg, 8.13 μmol), was added a solution of NMO (29.5 mg, 0.252 mmol) in acetone (2 ml) and H2O (0.16 ml). The reaction mixture was heated to 46° C. After stirring for 4 h, the solvent was removed and a mixture of THF (6 ml) and H2O (1.5 ml) was added to dissolve the residue, then sodium periodate (69.6 mg, 0.325 mmol) was added and the resulting mixture was stirred at 46° C. for 12 h. The reaction mixture was then quenched with Na2SO3(aq), extracted with DCM, dried over Na2SO4, filtered through Celite and concentrated in vacuo to give a residue, which was purified by silica gel column chromatography with gradient Hex:EA to give 3-((6-fluoro-1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine-6-carbaldehyde (20 mg), yield 38%. 1H-NMR (400 MHz, CDCl3) δ ppm 10.09 (s, 1H), 8.07 (dd, 1H), 7.89 (d, 1H), 7.74 (s, 1H), 7.63 (m, 2H), 7.10 (d, 1H), 4.54 (s, 2H), 4.03 (s, 3H). LCMS (method A): [MH]+=310, tR=3.95 min.

Workup

  1. customthe solvent was removed
  2. additiona mixture of THF (6 ml) and H2O (1.5 ml)
  3. additionwas added
  4. dissolutionto dissolve the residue
  5. stirringthe resulting mixture was stirred at 46° C. for 12 h
  6. customThe reaction mixture was then quenched with Na2SO3(aq)
  7. extractionextracted with DCM
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered through Celite
  10. concentrationconcentrated in vacuo
  11. customto give a residue, which
  12. customwas purified by silica gel column chromatography with gradient Hex

Sources & evidence

ORD record
ord-60d4abc7506f46cfb91f6e66da684a2d
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

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