Methyl iodide → HCID 57917420, compound

HRID 69244Notes

Reaction equation

HRID 69244 reaction equation
[H-].[Na+].[N:3]1[NH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[CH:9][C:8]([C@@H:12]([C:14]1[N:18]3[N:19]=[C:20]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:21]=[CH:22][C:17]3=[N:16][CH:15]=1)[CH3:13])=[CH:7]2.CI.[CH2:31](Cl)Cl>C1COCC1.[Cl-].[Na+].O>[CH3:31][N:3]1[C:11]2[C:6](=[CH:7][C:8]([C@@H:12]([C:14]3[N:18]4[N:19]=[C:20]([C:23]5[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=5)[CH:21]=[CH:22][C:17]4=[N:16][CH:15]=3)[CH3:13])=[CH:9][CH:10]=2)[CH:5]=[N:4]1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 178461646HCID 178461646, compound

Product 1

HCID 57917420HCID 57917420, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of NaH (4.8 mg, 0.1 mmol) in THF (0.5 mL) cooled to 0° C. was added (3-[(S)-1-(2H-indazol-5-yl)-ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 195, 34.3 mg, 0.10 mmol). The RM was allowed to warm up to rt and stirred 15 min. Then it was cooled down again and methyliodide (21.3 mg, 0.150 mmol) was added dropwise. The RM was allowed to warm up to rt and stirred for 5 h. It was then taken into DCM and brine, extracted, and the organics were joined dried over MgSO4. The solvent was removed and the residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in EtOAc) to afford the title compound after evaporation of the solvent and drying of the material under vacuum (tR 3.72 min (conditions 3), MH+=358, 1H-NMR in DMSO-d6: 8.35 (s, 1H); 8.03 (d, 1H); 8.00 (s, 1H); 7.94 (s, 1H); 7.73 (s, 1H); 7.70 (s, 1H); 7.52 (d, 1H); 7.45 (d, 1H); 7.43 (d, 1H); 4.73 (q, 1H); 4.74 (s, 3H); 3.89 (s, 3H); 1.77 (d, 3H)).

Workup

  1. temperatureto warm up to rt
  2. temperatureThen it was cooled down again
  3. temperatureto warm up to rt
  4. stirringstirred for 5 h
  5. extractionextracted
  6. dry with materialthe organics were joined dried over MgSO4
  7. customThe solvent was removed
  8. customthe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-6a7634ad9d40413c85553362341f9d65
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

Loading…