2-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → HCID 178449394, compound

HRID 246313

Reaction equation

HRID 246313 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14](Br)[N:15]=2)[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:26]([SiH2:30][O:31][C:32]([CH3:56])([CH3:55])[C:33]1[CH:34]=[CH:35][CH:36]=[C:37]2[C:41]=1[NH:40][N:39]=[C:38]2[Sn](CCCC)(CCCC)CCCC)([CH3:29])([CH3:28])[CH3:27]>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>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:38]3[C:37]4[C:41](=[C:33]([C:32]([CH3:56])([CH3:55])[O:31][SiH2:30][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:34]=[CH:35][CH:36]=4)[NH:40][N:39]=3)[N:15]=2)[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 178448228HCID 178448228, compound

Product 1

HCID 178449394HCID 178449394, compoundYield 34%

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 25 ml round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (180 mg, 0.42 mmol) and 7-(tert-butyldimethyl-silanyloxymethyl)-3-tributylstannanyl-1H-indazole (crude from Step 4, 462 mg, 0.50 mmol) were dissolved in DMF (2.8 ml). The reaction mixture was evacuated and backfilled with argon and tetrakis(triphenylphosphine)palladium (0) (25 mg, 0.022 mmol) and copper (I) iodide (16 mg, 0.084 mmol) were added. The reaction mixture was stirred at 80° C. overnight 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 concentrated. The residue was chromatographed over 25 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 86 mg (34%) of 2-[7-(tert-butyl-dimethyl-silanyloxymethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow solid.

Workup

  1. customThe reaction mixture was evacuated
  2. additionwere added
  3. temperaturethen cooled to room temperature
  4. customquenched with water
  5. extractionextracted with diethyl ether (2×)
  6. washThe combined organic layers were washed twice with water and once with brine
  7. concentrationthen concentrated
  8. customThe residue was chromatographed over 25 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc)

Sources & evidence

ORD record
ord-4fa93ed065c14364b79fe924fae5db38
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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