Water → 2-(5-cyano-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246294

Reaction equation

HRID 246294 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][N:27]1[C:35]2[C:30](=[CH:31][C:32]([C:36]#[N:37])=[CH:33][CH:34]=2)[C:29]([Sn](CCCC)(CCCC)CCCC)=[N:28]1.O.C(OCC)C>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:29]3[C:30]4[C:35](=[CH:34][CH:33]=[C:32]([C:36]#[N:37])[CH:31]=4)[N:27]([CH3:26])[N:28]=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

8

Reactant 4

HCID 962WaterHCID 3283Diethyl EtherHCID 712799231-methyl-3-tributylstannanyl-1H-indazole-5-carbonitrileHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712803922-(5-cyano-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 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 50 ml round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (300 mg, 0.70 mmol) and 1-methyl-3-tributylstannyl-1H-indazole-5-carbonitrile (crude from Step 3, 847 mg, 1.14 mmol) were dissolved in DMF (6.6 ml). The reaction mixture was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium (0) (41 mg, 0.036 mmol) and copper (I) iodide (27 mg, 0.14 mmol) were added. The reaction mixture was stirred at 80° C. overnight then cooled to room temperature and water and diethyl ether were added. The resulting brown precipitate was collected via filtration washing with water and diethyl ether. The brown powder was absorbed on silica gel and chromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-2% MeOH) to afford 254 mg (72%) of 2-(5-cyano-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow solid.

Workup

  1. customThe reaction mixture was evacuated
  2. temperaturethen cooled to room temperature
  3. filtrationThe resulting brown precipitate was collected via filtration
  4. washwashing with water and diethyl ether
  5. customThe brown powder was absorbed on silica gel
  6. customchromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-2% MeOH)

Sources & evidence

ORD record
ord-df763a4f79244485ac543daaa8dccf14
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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