6-fluoro-1-methyl-3-(tributylstannyl)-1H-indazole → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246560Notes

Reaction equation

HRID 246560 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.[F:26][C:27]1[CH:35]=[C:34]2[C:30]([C:31]([Sn](CCCC)(CCCC)CCCC)=[N:32][N:33]2[CH3:36])=[CH:29][CH:28]=1>CN(C=O)C.[Cu]I.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:31]3[C:30]4[C:34](=[CH:35][C:27]([F:26])=[CH:28][CH:29]=4)[N:33]([CH3:36])[N:32]=3)[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

6

Reactant 2

HCID 712803076-fluoro-1-methyl-3-(tributylstannyl)-1H-indazoleHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712798742-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 38%

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

2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (80 mg, 0.187 mmol) and 6-fluoro-1-methyl-3-(tributylstannyl)-1H-indazole (0.1 g, 0.228 mmol) were dissolved in DMF (3 mL). The reaction mixture was evacuated and filled with nitrogen. Copper(I) iodide (6.71 mg, 0.0749 mmol) and tetrakis(triphenylphosphine)palladium (0) (10.8 mg, 0.00936 mmol) were added. The reaction mixture was heated at 90° C. for 2 h. The mixture was cooled and partitioned between ethyl acetate and water, the organic phase washed with brine, then dried over magnesium sulfate. The crude compound was purified by chromatography using 25% ethyl acetate/hexanes to obtain 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (5 mg, 38%).

Workup

  1. customThe reaction mixture was evacuated
  2. additionfilled with nitrogen
  3. temperatureThe mixture was cooled
  4. custompartitioned between ethyl acetate and water
  5. washthe organic phase washed with brine
  6. dry with materialdried over magnesium sulfate
  7. customThe crude compound was purified by chromatography

Sources & evidence

ORD record
ord-82e55e0661674f19840937547bb45c5b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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