Isobutylamine → 2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isobutyl-amide

HRID 1677371Notes

Reaction equation

HRID 1677371 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[N:14]=[C:15]3[C:21]([C:22]([OH:24])=O)=[CH:20][NH:19][C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH2:25]([NH2:29])[CH:26]([CH3:28])[CH3:27].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.C(Cl)Cl>[NH4+:14].[OH-:2].[CH2:25]([NH:29][C:22]([C:21]1[C:15]2[C:16](=[N:17][CH:18]=[C:13]([C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:14]=2)[NH:19][CH:20]=1)=[O:24])[CH:26]([CH3:28])[CH3:27]

Participants

8

Reactant 4

HCID 6558IsobutylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 595407962-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 2

HCID 14923Ammonium HydroxideHCID 497644422-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isobutyl-amideYield 109.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (70 mg, 0.2 mmol), isobutylamine (44 μL, 0.42 mmol), 1-hydroxybenzotriazole hydrate (56 mg, 0.41 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (84 mg, 0.44 mmol) in DMF and CH2Cl2 was stirred at 70° C. overnight and partitioned between saturated NH4Cl and CH2Cl2. The aqueous layer was extracted with CH2Cl2 and the combined organic phases were washed with water, dried (Na2SO4), and concentrated. The residue was purified by preparative thin layer chromatography using 90:9.5:0.5 CH2Cl2:MeOH:concentrated aqueous NH4OH as eluant to afford 42 mg (50%) of 2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isobutyl-amide as a pale yellow powder. M+H 403.

Workup

  1. custompartitioned between saturated NH4Cl and CH2Cl2
  2. extractionThe aqueous layer was extracted with CH2Cl2
  3. washthe combined organic phases were washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by preparative thin layer chromatography

Sources & evidence

ORD record
ord-a0c9b8023de347eb8a987fab0773b396
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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