Cesium carbonate → 5-{2-[4-(4-Methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-pyrimidin-4-yl}-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 1619088Notes

Reaction equation

HRID 1619088 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2].I[C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)=[CH:21][C:20]=1[O:32][C:33]([F:36])([F:35])[F:34].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]4)=[CH:21][C:20]=3[O:32][C:33]([F:34])([F:36])[F:35])[N:12]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 666782975-(2-Amino-pyrimidin-4-yl)-1H-pyrrole-3-carboxylic acid ethyl esterHCID 666873781-(4-Iodo-3-trifluoromethoxy-phenyl)-4-methyl-piperazine

Product 1

HCID 666782405-{2-[4-(4-Methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-pyrimidin-4-yl}-1H-pyrrole-3-carboxylic acid ethyl esterYield 15%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-(2-amino-pyrimidin-4-yl)-1H-pyrrole-3-carboxylic acid ethyl ester (400 mg, 1.72 mmol) in dioxane (40 mL), 1-(4-iodo-3-trifluoromethoxy-phenyl)-4-methyl-piperazine (732 mg, 1.90 mmol) and cesium carbonate (1.1 g, 3.45 mmol) were added and the flask was evacuated and backfilled with argon. [Pd2(dba)3] (158 mg, 0.17 mmol) and Xantphos (299 mg, 0.52 mmol) were then charged and the mixture was heated at 80° C. under argon for 16 hours. After cooling to room temperature, the reaction mixture was concentrated, suspended in water (50 mL) and extracted with ethyl acetate. The organic phase was acidified on Na2SO4, filtered and evaporated to dryness, the crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5) to afford 126 mg (15% yield) of the title compound.

Workup

  1. customthe flask was evacuated
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction mixture was concentrated
  4. extractionextracted with ethyl acetate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customthe crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5)

Sources & evidence

ORD record
ord-c9b4a3d340904d6f86c308dffc97e8ff
Source dataset
uspto-grants-2014_07
Patent number
US08772280B2

Reaction notes

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