Aniline → HCID 57595741, compound

HRID 562856Notes

Reaction equation

HRID 562856 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17](Br)[CH:18]=3)[N:13]([Si](C(C)C)(C(C)C)C(C)C)[CH:12]=2)=[O:10])[CH:6]=[CH:7][CH:8]=1.[NH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([NH:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 23676156Sodium t-butoxideHCID 57595642HCID 57595642, compound

Product 1

HCID 57595741HCID 57595741, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

Compound 292 (135 mg, 0.2769 mmol) was dissolved in toluene (4.2 mL), under and atmosphere of argon. Aniline (0.154 mL, 1.69 mmol) and sodium tert-butoxide (57.7 mg, 0.60 mmol) were added to the reaction. Into the reaction was added tri-tert-butyl-phosphine (9.0 mg, 0.040 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (5.0 mg, 0.005 mmol). The reaction was heated at 95° C. for 18 hours. The solution was concentrated under reduced pressure. The remaining oil was partitioned between ethyl acetate and brine. The aqueous portion was extracted twice more with ethyl acetate. The organic portions were combined, dried with anhydrous magnesium sulfate, and concentrated to dryness. The residue was redissolved in ethyl acetate, adsorbed onto silica, and purified by silica gel flash chromatography with a step gradient of 50%-60% ethyl acetate:hexanes. The appropriate fractions were combined and concentrated to dryness to provide a light green solid. The solid was washed with hexanes and collected by filtration to provide compound 293 as a light green solid (26.6 mg, LRMS (ESI) [M+H+]+=344.1.)

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. customThe remaining oil was partitioned between ethyl acetate and brine
  3. extractionThe aqueous portion was extracted twice more with ethyl acetate
  4. dry with materialdried with anhydrous magnesium sulfate
  5. concentrationconcentrated to dryness
  6. dissolutionThe residue was redissolved in ethyl acetate
  7. custompurified by silica gel flash chromatography with a step gradient of 50%-60% ethyl acetate
  8. concentrationconcentrated to dryness
  9. customto provide a light green solid
  10. washThe solid was washed with hexanes
  11. filtrationcollected by filtration

Sources & evidence

ORD record
ord-14ae02209ade4f74853b58e9d27725e7
Source dataset
uspto-grants-2011_11
Patent number
US08067434B2

Reaction notes

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