HCID 71286034, compound → HCID 71288176, compound

HRID 245948Notes

Reaction equation

HRID 245948 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:12]=1)=[O:10])[CH3:7]>CO.C(OCC)(=O)C.[OH-].[OH-].[Pd+2]>[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:38])[CH3:37])[CH:12]=1)=[O:10])[CH3:7]

Participants

5

Reactant 1

HCID 71286034HCID 71286034, compound

Product 1

HCID 71288176HCID 71288176, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-furan-2-yl-ethyl)-amide (370 mg, 0.66 mmol) was dissolved in methanol (6 ml) and ethyl acetate (2 ml). The flask was flushed with argon then 20% palladium hydroxide on carbon (50% water, 100 mg, 0.71 mmol) was added. The reaction mixture was stirred under hydrogen atmosphere (balloon) at room temperature for 48 h then filtered over Celite and rinsed with dichloromethane/ethyl acetate. The filtrate was concentrated and the residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2.5% MeOH) to afford 300 mg (86%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(tetrahydro-furan-2-yl)-ethyl]-amide as a light yellow solid.

Workup

  1. customThe flask was flushed with argon
  2. filtrationthen filtered over Celite
  3. washrinsed with dichloromethane/ethyl acetate
  4. concentrationThe filtrate was concentrated
  5. customthe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2.5% MeOH)

Sources & evidence

ORD record
ord-d8187e9f7ee9402198f2f18232019b58
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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