Water → HCID 57917390, compound

HRID 69277Notes

Reaction equation

HRID 69277 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[CH2:11][C:12]1[N:16]2[N:17]=[C:18]([C:21]3[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=3)[CH:19]=[CH:20][C:15]2=[N:14][CH:13]=1.[H-].[Na+].I[CH3:30].O>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[CH2:11][C:12]1[N:16]2[N:17]=[C:18]([C:21]3[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=3)[CH:19]=[CH:20][C:15]2=[N:14][CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57917305HCID 57917305, compound

Product 1

HCID 57917390HCID 57917390, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-(6-Fluoro-1H-indazol-5-ylmethyl)-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 167, 18.6 mg, 0.054 mmol) was dissolved in DMF (0.310 mL) and cooled down to 0° C. NaH (1.9 mg, 0.080 mmol) was added and the RM was stirred for 30 min. Then iodomethane (4.02 μL) was introduced and it was allowed to warm up to rt. After 2.5 h of stirring, water was added and it was extracted with EtOAc. Organic layer was washed with brine and dried over Na2SO4, filtered and concentrated. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and were lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt of the title compound as a white solid (tR 1.0 min (conditions 2), MH+=362).

Workup

  1. temperatureto warm up to rt
  2. stirringAfter 2.5 h of stirring
  3. extractionit was extracted with EtOAc
  4. washOrganic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  9. dissolutionThe residue was dissolved in MeOH
  10. customto remove the TFA salt
  11. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-a001589bfc92439683cfc2606376027e
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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