Potassium Carbonate → 5-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 1619083Notes

Reaction equation

HRID 1619083 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH2:16].[CH2:17]([O:19][C:20]([C:22]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][N:30]=[C:29](I)[N:28]=2)[N:24]([CH3:34])[CH:23]=1)=[O:21])[CH3:18].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:17]([O:19][C:20]([C:22]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:16][C:4]3[CH:5]=[CH:6][C:7]([N:9]4[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]4)=[CH:8][C:3]=3[O:2][CH3:1])[N:28]=2)[N:24]([CH3:34])[CH:23]=1)=[O:21])[CH3:18]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 201362532-Methoxy-4-(4-methylpiperazin-1-yl)anilineHCID 866631235-(2-iodo-pyrimidin-4-yl)-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 666782985-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid ethyl esterYield 26.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent2×

Procedure

Palladium acetate [Pd(OAc)2] (60 mg, 0.271 mmol), (±)-BINAP (169 mg, 0.271 mmol) and dimethylformamide (15 mL) were charged to a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. The mixture was stirred under argon for 30 minutes and added to a mixture of 2-methoxy-4-(4-methyl-piperazin-1-yl)-phenylamine (600 mg, 2.712 mmol), 5-(2-iodo-pyrimidin-4-yl)-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (484 mg, 1.356 mmol), and potassium carbonate (1.87 g, 13.56 mmol) in dimethylformamide (15 mL). The resulting mixture was stirred at 80° C. for 4 hours under argon. After cooling to room temperature, the reaction mixture was filtered on a pad of celite. The solvent was concentrated, the crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5) to afford 160 mg (26%) of the title compound as white solid.

Workup

  1. customflushed with argon
  2. customThe flask was evacuated
  3. stirringThe resulting mixture was stirred at 80° C. for 4 hours under argon
  4. filtrationthe reaction mixture was filtered on a pad of celite
  5. concentrationThe solvent was concentrated
  6. customthe crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5)

Sources & evidence

ORD record
ord-9a4ec9825a7741d9b375c4d3be3226fd
Source dataset
uspto-grants-2014_07
Patent number
US08772280B2

Reaction notes

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