Methylamine → 5-bromo-2-(4-fluorophenyl)-N-methyl-1H-indole-3-carboxamide

HRID 219337Notes

Reaction equation

HRID 219337 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=[C:5]2[C:18]([O:20]CC)=O.B(Br)(Br)Br.C(Cl)Cl.[CH3:30][NH2:31].C1COCC1>ClCCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=[C:5]2[C:18]([NH:31][CH3:30])=[O:20]

Participants

7

Reactant 5

HCID 6329MethylamineHCID 6344DichloromethaneHCID 8028TetrahydrofuranHCID 25134Boron tribromideHCID 59233823ethyl 5-bromo-2-(4-fluorophenyl)-1H-indole-3-carboxylate

Product 1

HCID 592338075-bromo-2-(4-fluorophenyl)-N-methyl-1H-indole-3-carboxamideYield 70%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A suspension of ethyl 5-bromo-2-(4-fluorophenyl)-1H-indole-3-carboxylate (90 mg, 0.25 mmol) in 1,2-dichloroethane (3 mL) was cooled in an ice bath under an atmosphere of N2. A solution of boron tribromide in CH2Cl2 (1 M, 0.75 mL, 0.75 mmol) was added the reaction was allowed warm to r.t. under N2 over 4 h. Then the reaction was then quenched by the addition of a solution of methylamine in THF (2 M, 5 mL, 10 mmol). The reaction was partitioned between EtOAc and water, the organic phase was washed with water and brine, dried over Na2SO4, filtered, and concentrated to give a colorless oil. Et2O/hexanes was added and a white precipitate formed. The powder was collected by filtration, washed with Et2O, and air dried to give the title compound (60 mg, 70% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.93 (s, 1H) 7.82 (d, J=1.83 Hz, 1H) 7.71-7.78 (m, 3H) 7.32-7.41 (m, 3H) 7.29 (dd, J=8.55, 1.83 Hz, 1H) 2.75 (d, J=4.58 Hz, 3H). LC/MS was performed on a Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=5% CH3CN/95% H2O/10 mM NH4OAc, solvent B=95% CH3CN/5% H2O/10 nM NH4OAc, start % B=0, final % B=100, gradient time=2 min, stop time=3 mM, flow rate=5 ml/min, column: XBridge C18 5 μm 4.6×50 mm; HPLC Rt=1.26, (ES+) m/z (MH+)=347, 349 (1:1 ratio).

Workup

  1. temperaturewas cooled in an ice bath under an atmosphere of N2
  2. customThe reaction was partitioned between EtOAc and water
  3. washthe organic phase was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a colorless oil
  8. customa white precipitate formed
  9. filtrationThe powder was collected by filtration
  10. washwashed with Et2O, and air
  11. customdried

Sources & evidence

ORD record
ord-01d715edbb5c43c6b1596e0e5a894028
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

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