Potassium Phosphate, Tribasic → 2-(1,3-dimethyl-1H-pyrazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 1898667Notes

Reaction equation

HRID 1898667 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[C:4]([CH3:16])=[N:3]1.[Cl-].[Li+].Br[C:20]1[N:21]=[C:22]2[C:28]([CH:29]=[O:30])=[CH:27][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:23]2=[N:24][CH:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C(OCC)(=O)C.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.C1(C)C=CC=CC=1.C(O)C>[CH3:1][N:2]1[CH:6]=[C:5]([C:20]2[N:21]=[C:22]3[C:28]([CH:29]=[O:30])=[CH:27][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:23]3=[N:24][CH:25]=2)[C:4]([CH3:16])=[N:3]1

Participants

10

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 433294Lithium ChlorideHCID 426473161,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 584385862-(1,3-dimethyl-1H-pyrazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeYield 78.8%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
62.5 °C

Procedure

In a 25 mL pressure vessel, 1,3-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (439 mg, 1.98 mmol), lithium chloride (52 mg, 1.23 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (440 mg, 1.23 mmol) were combined with ethanol (7 mL) and toluene (7 mL) and the mixture was purged with N2. Potassium phosphate tribasic (917 mg, 4.32 mmol) was dissolved in 4 mL water and added to the mixture. After more purging with N2 bis(triphenylphosphine)palladium (II) dichloride (87 mg, 0.12 mmol) was added, the vessel capped and stirred at 60-65° C. for 20 h. The reaction was cooled, then diluted with ethyl acetate and water. The organic layer was washed with brine, dried and evaporated. The crude material was purified by flash chromatography (silica gel, 80 g, 100% EtOAc to 20% THF/EtOAc) to give 360 mg (71% yield; 90% purity) of 2-(1,3-dimethyl-1H-pyrazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde.

Workup

  1. customthe mixture was purged with N2
  2. additionadded to the mixture
  3. additionwas added
  4. customthe vessel capped
  5. temperatureThe reaction was cooled
  6. washThe organic layer was washed with brine
  7. customdried
  8. customevaporated
  9. customThe crude material was purified by flash chromatography (silica gel, 80 g, 100% EtOAc to 20% THF/EtOAc)

Sources & evidence

ORD record
ord-f37eea6e6098489683ba9b150b5427a1
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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