2-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → 2-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 245954Notes

Reaction equation

HRID 245954 reaction equation
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13](Br)[N:14]=2)[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:8]=1)=[O:6])([CH3:3])[CH3:2].[C:25]([Si:29]([CH3:55])([CH3:54])[O:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[N:36]([CH3:40])[N:35]=[C:34]2[Sn](CCCC)(CCCC)CCCC)([CH3:28])([CH3:27])[CH3:26]>CN(C=O)C.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.[Cu]I>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:34]3[C:33]4[C:37](=[CH:38][CH:39]=[C:31]([O:30][Si:29]([C:25]([CH3:27])([CH3:26])[CH3:28])([CH3:54])[CH3:55])[CH:32]=4)[N:36]([CH3:40])[N:35]=3)[N:14]=2)[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 585222792-bromo-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 712796055-(tert-butyldimethylsilyloxy)-1-methyl-3-(tributylstannyl)-1H-indazole

Product 1

HCID 712796602-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamideYield 72%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

In a round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (100 mg, 0.24 mmol) and 5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-3-tributylstannanyl-1H-indazole (crude from Step 4) were dissolved in DMF (2 ml). The flask was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium (0) (14 mg, 0.012 mmol) and copper (I) iodide (10 mg, 0.053 mmol) were added. The reaction mixture was stirred at 80° C. for 2 h then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-30% EtOAc) to afford 104 mg (72%) of 2-[5-(tert-butyl-dimethyl-silanyloxy)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a light yellow solid.

Workup

  1. customThe flask was evacuated
  2. temperaturethen cooled to room temperature
  3. customquenched with water
  4. extractionextracted with diethyl ether (2×)
  5. washThe combined organic layers were washed twice with water and once with brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-30% EtOAc)

Sources & evidence

ORD record
ord-8535c24e3eda4f2e85bc72f1eafc80c1
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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