Methyl iodide → HCID 57917387, compound

HRID 69238Notes

Reaction equation

HRID 69238 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[C@@H:11]([C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1)[CH3:12].[H-].[Na+].[CH3:30]I>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:30])=[CH:4][C:3]=1[C@@H:11]([C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1)[CH3:12]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57917484HCID 57917484, compound

Product 1

HCID 57917387HCID 57917387, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-[(S)-1-(6-Fluoro-1H-indazol-5-yl)-ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 165, 23 mg, 0.065 mmol) was dissolved in DMF (0.374 mL) and cooled down to 0° C. under nitrogen conditions. NaH (3.82 mg, 0.095 mmol) was added and the RM was stirred at 0° C. for 30 min. Then methyliodide (10.84 mg, 0.076 mmol) was introduced. The RM was allowed to warm up to rt and stirred for 2.5 h, then it was quenched with water. It was extracted twice with EtOAc. The organics were joined and washed with brine, dried over Na2SO4. The solvent was removed and the residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The acetonitrile was removed and the aqueous solution was basified with 5% NaHCO3. It was extracted twice with EtOAc and then the organics were joined and washed with brine. It was dried over Na2SO4 and the solvent was removed. The residue was triturated with pentane and the precipitate was filtered off to afford the title compound as a white solid (tR 1.0 min (conditions 2), MH+=376, 1H-NMR in DMSO-d6: 8.30 (s, 1H); 8.06 (d, 1H); 7.94 (s, 2H); 7.67 (s, 1H); 7.59 (d, 1H); 7.54 (d, 1H); 7.46 (d, 1H); 4.95 (q, 1H); 3.95 (s, 3H); 3.88 (s, 3H); 1.77 (d, 3H)).

Workup

  1. temperatureto warm up to rt
  2. stirringstirred for 2.5 h
  3. customit was quenched with water
  4. extractionIt was extracted twice with EtOAc
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed
  8. customthe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  9. customThe acetonitrile was removed
  10. extractionIt was extracted twice with EtOAc
  11. washwashed with brine
  12. dry with materialIt was dried over Na2SO4
  13. customthe solvent was removed
  14. customThe residue was triturated with pentane
  15. filtrationthe precipitate was filtered off

Sources & evidence

ORD record
ord-e1848a9c3be8481cb1e766bc0f52f27f
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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