Potassium Carbonate → 2-(1-Ethyl-1H-pyrazol-4-yl)-5-[[2-(trimethylsilyl)ethoxy]methyl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxaldehyde

HRID 1898491Notes

Reaction equation

HRID 1898491 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.[CH2:21]([N:23]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[N:24]1)[CH3:22].C([O-])([O-])=O.[K+].[K+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:21]([N:23]1[CH:27]=[C:26]([C:2]2[N:3]=[C:4]3[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]3=[N:6][CH:7]=2)[CH:25]=[N:24]1)[CH3:22]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 866578682-(1-Ethyl-1H-pyrazol-4-yl)-5-[[2-(trimethylsilyl)ethoxy]methyl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxaldehydeYield 81%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (1.33 g, 3.73 mmol) and 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (995 mg, 4.48 mmol) in 1,2-DME (20 mL) were added Pd(Ph3P)4 (0.22 g, 0.19 mmol) and 2.0 M aqueous K2CO3 (5.6 ml, 11.2 mmol). The reaction mixture was degassed by bubbling N2 for 15 min then heated at 100° C. overnight. The resultant maroon reaction mixture was cooled and diluted with H2O then extracted with EtOAc (2×). The combined organics were dried over MgSO4 and concentrated. The crude residue was purified by SiO2 chromatography (30% to 80% EtOAc/hexanes) to afford 1.12 g (81%) of 2-(1-ethyl-1H-pyrazol-4-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a light orange-brown solid.

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling N2 for 15 min
  3. customThe resultant maroon reaction mixture
  4. temperaturewas cooled
  5. extractionthen extracted with EtOAc (2×)
  6. dry with materialThe combined organics were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude residue was purified by SiO2 chromatography (30% to 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6a686379d56c4bbab0bc5de75acec457
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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