Ethyl Acetate → (Rac)-1-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-ethanol

HRID 69240Notes

Reaction equation

HRID 69240 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[CH:22]=[CH:21][C:20]4[C:16](=[CH:17][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:19]=4)[CH:15]=3)([OH:13])[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>COCCOC.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:31][N:32]1[CH:36]=[C:35]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C:11]([C:14]4[CH:22]=[CH:21][C:20]5[C:16](=[CH:17][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:19]=5)[CH:15]=4)([OH:13])[CH3:12])=[CH:9][N:10]=3)[N:7]=2)[CH:34]=[N:33]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 87523960(Rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-ethanol

Product 1

HCID 68640428(Rac)-1-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2h-indazol-5-yl]-ethanol

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazol-5-yl]-ethanol (Stage 195.2, 400 mg, 0.901 mmol) in DME (4 mL) degassed with argon was added 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (281 mg, 1.351 mmol), followed by 2 M K2CO3 (1.216 mL) and PdCl2(PPh3)2 (19 mg). The RM was heated at 80° C. for 5 h. It was then taken into EtOAc and brine and extracted. Combined organic layers were dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH=100:0->80:20) to afford the title compound (tR 4.56 min (conditions 3), MH+=490).

Workup

  1. extractionextracted
  2. dry with materialCombined organic layers were dried over Na2SO4
  3. customevaporated
  4. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH=100:0->80:20)

Sources & evidence

ORD record
ord-3d0cae261860409bab8da9ec29a3a3b4
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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