Ethyl Acetate → (Rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-ethanol

HRID 69241Notes

Reaction equation

HRID 69241 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:13]3[CH:21]=[CH:20][C:19]4[C:15](=[CH:16][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[N:18]=4)[CH:14]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:30][Mg]Br.CCOC(C)=O>C1COCC1.CCOCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:13]3[CH:21]=[CH:20][C:19]4[C:15](=[CH:16][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[N:18]=4)[CH:14]=3)([OH:12])[CH3:30])=[CH:9][N:10]=2)[N:7]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 87523378(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-methanoneHCID 178418573HCID 178418573, compound

Product 1

HCID 87523960(Rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-ethanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazol-5-yl]-methanone (Stage 195.3, 539 mg, 1.259 mmol) in THF (50 mL) was added dropwise at rt a solution of methylmagnesium bromide in Et2O (3 M, 0.462 mL). After 30 min stirring, the RM was taken into EtOAc and washed with a 10% NaHCO3 solution and then with brine. The organic layer was dried over Na2SO4 and the solvent was evaporated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, n-hexane/EtOAc=95:5->0:100) to afford after recrystallisation in pentane with a little EtOAc the title compound as a light yellowish powder (tR 5.6 min (conditions 3), MH+=444).

Workup

  1. washwashed with a 10% NaHCO3 solution
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customthe solvent was evaporated
  4. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, n-hexane/EtOAc=95:5->0:100)
  5. customto afford
  6. customafter recrystallisation in pentane with a little EtOAc the title compound as a light yellowish powder (tR 5.6 min (conditions 3), MH+=444)

Sources & evidence

ORD record
ord-5a8ddace40b64fe28897e3835299de24
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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