Potassium Carbonate → 1-{2-[6-amino-5-(methyloxy)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-pyrrolidinol

HRID 1014317Notes

Reaction equation

HRID 1014317 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+].[NH:25]1[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26]1>ClCCl.O>[NH2:14][C:11]1[CH:12]=[C:13]2[C:8]([CH2:7][CH2:6][N:5]2[C:3](=[O:4])[CH2:2][N:25]2[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26]2)=[CH:9][C:10]=1[O:17][CH3:18]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 982104-HydroxypyrrolidineHCID 594418341-(bromoacetyl)-5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole

Product 1

HCID 594420191-{2-[6-amino-5-(methyloxy)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-pyrrolidinolYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

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 3-pyrrolidinol (1.33 g, 15.2 mmol) in 10 mL dichloromethane were added, and the reaction was stirred at RT overnight. The reaction mixture was diluted with 100 mL of water, the organic solvents were washed with water (2×100 mL), dried over Na2SO4, and the solvent was removed under reduced pressure. The resulting residue 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, and the reaction was stirred at RT overnight under a balloon of H2 pressure. The catalyst was removed via filtration and the solvent was evaporated under reduced pressure to yield the 1-{2-[6-amino-5-(methyloxy)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-pyrrolidinol as a white solid (3.0 g, 92%).1H NMR (400 MHz, DMSO-d6) δ ppm: 1.60 (m, 1 H), 1.97 (m, 1 H), 2.47(s, 1H), 2.59 (m, 1 H), 2.72 (m, 1 H), 2.85 (m, 1 H), 2.96 (m, 4 H), 3.50(s, 2H), 3.68(s, 3H), 4.00 (t, J=8.33 Hz, 2 H), 4.86 (s, 2H), 6.68 (s, 1 H), 7.51 (s, 1 H).

Workup

  1. washthe organic solvents were washed with water (2×100 mL)
  2. dry with materialdried over Na2SO4
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe resulting residue was dissolved in 10 mL of EA
  5. addition25 mL of MeOH and 15 mL of THF, then 0.8 g 10% Pd/C was added
  6. stirringthe reaction was stirred at RT overnight under a balloon of H2 pressure
  7. customThe catalyst was removed via filtration
  8. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bb6508a9c146461589866c245d60c50d
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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