Ammonium Chloride → (Rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-methanol

HRID 69243

Reaction equation

HRID 69243 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C([Mg]Br)C.[CH3:16][Si:17]([CH3:34])([CH3:33])[CH2:18][CH2:19][O:20][CH2:21][N:22]1[CH:30]=[C:29]2[C:24]([CH:25]=[CH:26][C:27]([CH:31]=[O:32])=[CH:28]2)=[N:23]1.[NH4+].[Cl-]>C1COCC1.CCOCC>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH:31]([C:27]3[CH:26]=[CH:25][C:24]4[C:29](=[CH:30][N:22]([CH2:21][O:20][CH2:19][CH2:18][Si:17]([CH3:34])([CH3:33])[CH3:16])[N:23]=4)[CH:28]=3)[OH:32])=[CH:3][N:4]=2)[N:7]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 866351152-(2-Trimethylsilanyl-ethoxymethyl)-2H-indazole-5-carbaldehydeHCID 178418443HCID 178418443, compound

Product 1

HCID 87523362(Rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-methanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-bromo-6-chloro-imidazo[1,2-b]pyridazine (465 mg, 2.0 mmol) in THF (60 mL) was added dropwise at rt a solution of ethylmagnesium bromide in Et2O (3 M, 1.0 mL). The temperature rose slightly (up to 27° C.) and the RM was stirred 15 min. Then a solution of 2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazole-5-carbaldehyde (Stage 150.4, 829 mg, 3.00 mmol) in THF (8 mL) was added dropwise and the RM was then stirred 2 h at rt. The RM was then taken into a solution of NH4Cl and extracted with EtOAc. Combined organic layers were washed with brine, dried over Na2SO4 and the solvent was removed. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, n-hexane/EtOAc=95:5->0:100) to afford the title compound as a light brown thick oil (tR 5.35 min (conditions 3), MH+=430).

Workup

  1. customup to 27° C.
  2. stirringthe RM was then stirred 2 h at rt
  3. extractionextracted with EtOAc
  4. washCombined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was removed
  7. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, n-hexane/EtOAc=95:5->0:100)

Sources & evidence

ORD record
ord-8bf8342225db4c129d67bcdb92bccc82
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Linked notes

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