6-methanesulfonyl-1-methyl-3-tributylstannanyl-1H-indazole → 2-(6-methanesulfonyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246326

Reaction equation

HRID 246326 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].[CH3:26][S:27]([C:30]1[CH:38]=[C:37]2[C:33]([C:34]([Sn](CCCC)(CCCC)CCCC)=[N:35][N:36]2[CH3:39])=[CH:32][CH:31]=1)(=[O:29])=[O:28]>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:34]3[C:33]4[C:37](=[CH:38][C:30]([S:27]([CH3:26])(=[O:28])=[O:29])=[CH:31][CH:32]=4)[N:36]([CH3:39])[N:35]=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 712801606-methanesulfonyl-1-methyl-3-tributylstannanyl-1H-indazoleHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712801592-(6-methanesulfonyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 55%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

In a round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (110 mg, 0.26 mmol) and 6-methanesulfonyl-1-methyl-3-tributylstannanyl-1H-indazole (crude from Step 3, 330 mg, 0.33 mmol) were dissolved in DMF (1.7 ml). The flask was evacuated and backfilled with argon and tetrakis(triphenylphosphine)palladium (0) (15 mg, 0.013 mmol) and copper (I) iodide (10 mg, 0.053 mmol) were added. The reaction mixture was stirred at 90° C. for 3 h then allowed to cool to room temperature overnight. The reaction was quenched with water and extracted with diethyl ether (2×) and EtOAc. 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 25 g silica gel with EtOAc/hexanes (gradient: 0-40% EtOAc) to afford 79 mg (55%) of 2-(6-methanesulfonyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light brown solid.

Workup

  1. customThe flask was evacuated
  2. additionwere added
  3. temperatureto cool to room temperature overnight
  4. customThe reaction was quenched with water
  5. extractionextracted with diethyl ether (2×) and EtOAc
  6. washThe combined organic layers were washed twice with water and once with brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was chromatographed over 25 g silica gel with EtOAc/hexanes (gradient: 0-40% EtOAc)

Sources & evidence

ORD record
ord-66a6290a6a7948bda8e9e0126da18aa1
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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