Methanol → 1-{[ethyl(methyl)amino]acetyl}-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine

HRID 1014314Notes

Reaction equation

HRID 1014314 reaction equation
Br[CH2:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:17][CH3:18])=[C:11]([N+:14]([O-])=O)[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH3:25][NH:26][CH2:27][CH3:28].CO>ClCCl.CC(=O)OCC.[Pd].C1COCC1>[CH2:27]([N:26]([CH2:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:17][CH3:18])=[C:11]([NH2:14])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4])[CH3:25])[CH3:28]

Participants

9

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 12219N-MethylethylamineHCID 594418341-(bromoacetyl)-5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole

Product 1

HCID 594420161-{[ethyl(methyl)amino]acetyl}-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The 1-(bromoacetyl)-5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole (4.0 g, 12.7 mmol) was dissolved in 50 mL of dichloromethane, then K2CO3 (4.4 g, 31.7 mmol) and N-methylethanamine(1.5 g, 25.4 mmol) in 10 mL dichloromethane were added and the reaction was stirred at RT for 3 hours. After filtration, the organic layers were washed with water (2×100 mL) and dried over Na2SO4. The solvent was was removed under reduced pressure and the derived residue (3.4 g, 11.59 mmol) was dissolved in 10 mL of EA, 25 mL of MeOH and 15 mL of THF, then 0.8 g 10% Pd/C was added, the reaction was stirred at RT overnight under H2 pressure (65 psi). The catalyst was removed via filteration, and the solvent was evaporated under reduced pressure to afford 1-{[ethyl(methyl)amino]acetyl}-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine as a yellow solid, 3.0 g (97%).1HNMR (400 MHz, DMSO-d6) δ ppm: 0.97 (t, J=7.14 Hz, 3H), 2.20 (s, 3H), 2.46(m, 2H), 2.94 (t, 2 H), 3.16(s, 2H), 3.68 (s, 3H), 4.06 (t, J=8.42 Hz, 2 H), 4.60 (s, 2H), 6.67 (s, 1 H), 7.52 (s, 1 H).

Workup

  1. filtrationAfter filtration
  2. washthe organic layers were washed with water (2×100 mL)
  3. dry with materialdried over Na2SO4
  4. customThe solvent was was removed under reduced pressure
  5. stirringthe reaction was stirred at RT overnight under H2 pressure (65 psi)
  6. customThe catalyst was removed via filteration
  7. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-3a358f2a1b3f49efad154a9ef3abcf17
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

Loading…