Aniline → 8-bromo-3-methyl-N-phenylquinolin-2-amine

HRID 1055929Notes

Reaction equation

HRID 1055929 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18](Cl)[C:17]([CH3:22])=[CH:16]2>CN(C=O)C>[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:17]([CH3:22])=[CH:16]2

Participants

5

Reactant 3

HCID 6115AnilineHCID 24758Sodium hydrideHCID 632320088-Bromo-2-chloro-3-methylquinoline

Product 1

HCID 897822388-bromo-3-methyl-N-phenylquinolin-2-amineYield 28.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaH (60% w/w in mineral oil; 390 mg, 9.75 mmol) was added to a solution of aniline (0.888 mL, 9.75 mmol) in DMF (4.0 mL) at 0° C. and the resulting suspension was stirred at 0° C. for 2 min, then warmed to 25° C. and stirred for 5 min. 8-Bromo-2-chloro-3-methylquinoline (Example 104b; 529 mg, 2.062 mmol) was added as a solid, and the resulting solution was stirred at 25° C. for 1.5 h, then at 80° C. bath for 2.5 h. The mixture was cooled to 25° C. and partitioned between EtOAc (100 mL) and saturated aq. NH4Cl (80 mL). The organic layer was separated and the aq. layer was extracted with EtOAc (2×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-40% EtOAc/hexanes) furnished 8-bromo-3-methyl-N-phenylquinolin-2-amine (182.0 mg, 0.581 mmol, 28% yield) as a brown oil: m/z (ESI, +ve) 313.1 (M+H)+.

Workup

  1. temperaturewarmed to 25° C.
  2. stirringstirred for 5 min
  3. stirringthe resulting solution was stirred at 25° C. for 1.5 h
  4. waitat 80° C. bath for 2.5 h
  5. temperatureThe mixture was cooled to 25° C.
  6. custompartitioned between EtOAc (100 mL) and saturated aq. NH4Cl (80 mL)
  7. customThe organic layer was separated
  8. extractionthe aq. layer was extracted with EtOAc (2×50 mL)
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customChromatographic purification of the residue (silica gel, 0-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-11ae0bc1137b4683873a5fe03d6cd69f
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…