Potassium Carbonate → HCID 71279970, compound

HRID 246436Notes

Reaction equation

HRID 246436 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:32][C:33]1[NH:34][C:35]2[C:40]([CH:41]=1)=[CH:39][CH:38]=[CH:37][C:36]=2B1OC(C)(C)C(C)(C)O1.CN1C2C(=CC=CC=2B2OC(C)(C)C(C)(C)O2)C=C1>O1CCOCC1.C(OCC)(=O)C.CCOCC.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>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:36]3[CH:37]=[CH:38][CH:39]=[C:40]4[C:35]=3[NH:34][C:33]([CH3:32])=[CH:41]4)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 249605942-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 707001311-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71279970HCID 71279970, compoundYield 73.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (79 mg, 185 μmol), potassium carbonate (51.1 mg, 370 μmol) and 2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (95.1 mg, 370 μmol) were dissolved in dioxane (5 mL) and water (0.5 mL), then the reaction was purged with nitrogen for 1 minute. Tetrakis(triphenylphosphine)palladium(0) (21.4 mg, 18.5 μmol) was then added, and the reaction was placed under a nitrogen atmosphere and the mixture heated at to 80° C. for 2 h. Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (45 mg), was added and the reaction was heated at 80° C. for an additional 2 h. The reaction mixture was cooled, diluted with ethyl acetate/ether (ca 3:1), washed water and brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by chromatography (silica gel, 3-15% ethyl acetate in hexanes) to give N-tert-butyl-2-(2-methyl-1H-indol-7-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (65 mg) as an oil. MS (M+H)+=478.3.

Workup

  1. customwater (0.5 mL), then the reaction was purged with nitrogen for 1 minute
  2. temperaturethe reaction was heated at 80° C. for an additional 2 h
  3. temperatureThe reaction mixture was cooled
  4. washwashed water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by chromatography (silica gel, 3-15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-acc7fcafef77470e94fe641360589037
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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