Potassium Carbonate → N-tert-butyl-2-(1H-indol-7-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246438Notes

Reaction equation

HRID 246438 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.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[CH:36][CH:37]=[C:38]3[C:42]=2[NH:41][CH:40]=[CH:39]3)O1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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.O>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:34]3[CH:35]=[CH:36][CH:37]=[C:38]4[C:42]=3[NH:41][CH:40]=[CH:39]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

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 112650167-(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 71280445N-tert-butyl-2-(1H-indol-7-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 99.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (50 mg, 117 μmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (37.0 mg, 152 μmol), potassium carbonate (16.2 mg, 117 μmol) were combined in a reaction tube with a teflon-threaded seal, dioxane (2.5 mL) and water (0.5 mL) were added, then the mixture degassed with nitrogen for 1 min. Tetrakis(triphenylphosphine)palladium(0) (13.5 mg, 11.7 μmol) was added, nitrogen was bubbled through for 1 minute, then the reaction was heated to 85° C. for 6 h, and then at 75° C. for an additional 15 h. The reaction mixture was cooled, concentrated in vacuo, and the residue purified by chromatography (silica, 1-15% ethyl acetate in hexanes) to give N-tert-butyl-2-(1H-indol-7-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (54 mg) as an oil which slowly crystallized. MS (M+H)+=464.2.

Workup

  1. customthreaded seal
  2. customthe mixture degassed with nitrogen for 1 min
  3. customnitrogen was bubbled through for 1 minute
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated in vacuo
  6. customthe residue purified by chromatography (silica, 1-15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9a98c3f972b846d28834a4bdc1b6d175
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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