Aniline → HCID 70670709, compound

HRID 1894978Notes

Reaction equation

HRID 1894978 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([O:14][CH3:15])=[O:13])=[CH:5]2.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:17]1([NH:16][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12]([O:14][CH3:15])=[O:13])=[CH:5]3)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 53465709Methyl 6-bromoquinoline-3-carboxylate

Product 1

HCID 70670709HCID 70670709, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 6-bromoquinoline-3-carboxylate (Int-1, 0.25 g, 0.94 mmol), aniline (94 μL, 1.0 mmol), palladium(II) acetate (21 mg, 0.094 mmol), 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine) (43 mg, 0.070 mmol), and cesium carbonate (431 mg, 1.32 mmol) were combined in a microwave vial fitted with a stirbar. N,N-Dimethylformamide (5.5 mL) was added, the vial was capped and the contents heated in a microwave at 100° C. for 1 h. The vial was cooled to room temperature, opened and the contents poured into water. The mixture was extracted three times with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (hexanes to 70/30 hexanes/ethyl acetate gradient) to afford pure Int-34. LC-MS: (FA) ES+ 279; 1H NMR (400 MHz, d6-DMSO) δ ppm 9.02 (d, J=2.1 Hz, 1 H), 8.79-8.74 (m, 2H), 7.94 (d, J=9.0 Hz, 1H), 7.67 (d, J=2.5 Hz, 1H), 7.62 (dd, J=9.1, 2.6 Hz, 1 H), 7.35-7.29 (m, 2H), 7.29-7.25 (m, 2H), 6.96 (tt, J=7.4, 7.4, 1.3, 1.3 Hz, 1H), 3.92 (s, 3H).

Workup

  1. customvial fitted with a stirbar
  2. customthe vial was capped
  3. temperatureThe vial was cooled to room temperature
  4. extractionThe mixture was extracted three times with ethyl acetate
  5. washThe extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified by silica gel chromatography (hexanes to 70/30 hexanes/ethyl acetate gradient)
  10. customto afford pure Int-34

Sources & evidence

ORD record
ord-49aa6f830a7a42d3861e5a344ae28019
Source dataset
uspto-grants-2013_08
Patent number
US08513421B2

Reaction notes

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