Dimethylformamide → 3-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetate

HRID 516765Notes

Reaction equation

HRID 516765 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:13]([O:15][CH3:16])=[O:14])[C:7]2[CH:8]=[CH:9][NH:10][C:11]=2[CH:12]=1.Br[CH:18]([CH2:20][CH3:21])[CH3:19].[CH3:22][N:23]([CH:25]=[O:26])C>O>[Br:3][C:4]1[CH:5]=[C:6]([C:13]([O:15][CH3:16])=[O:14])[C:7]2[CH:8]=[CH:9][N:10]([CH:18]([CH2:20][CH3:21])[CH3:19])[C:11]=2[CH:12]=1.[NH2:10][CH2:9][C:8]1[C:25](=[O:26])[NH:23][C:22]([CH3:18])=[CH:11][C:7]=1[CH2:6][CH2:5][CH3:4]

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 65542-BromobutaneHCID 24758Sodium hydrideHCID 13770009methyl 6-bromo-1H-indole-4-carboxylate

Product 2

HCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateYield 40.1%HCID 67466396Methyl 6-bromo-1-(sec-butyl)-1H-indole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred suspension of sodium hydride (5.66 g, 141.7 mmol) in DMF (100 mL) was added a solution of methyl 6-bromo-1H-indole-4-carboxylate (4) (30 g, 118.1 mmol) in DMF (50 mL) at 0° C. and stirred for 20 min. Then 2-Bromo butane (29.1 g, 212.5 mmol) was added at 0° C. and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with cold water and extracted with ethyl acetate (4×150 mL). The combined organic layer was washed with cold water (150 mL), brine (100 mL) and dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude, which was purified by column chromatography over silica gel (60-120 mesh) using 5% EtOAc: Pet ether as eluent to afford the title compound methyl 6-bromo-1-sec-butyl-1H-indole-4-carboxylate, 5 (14 g, 40.1%) as pale yellow solid. 1H NMR (CDCl3, 400 MHz) δ 0.843-0.870 (m, 3H), 1.512 (d, J=6.4 Hz, 3H), 1.844-1.926 (m, 2H), 3.976 (s, 3H), 4.333-4.385 (m, 1H), 7.132 (d, J=3.2 Hz, 1H), 7.302 (d, J=3.6 Hz, 1H), 7.707 (s, 1H), 7.984 (d, J=1.6 Hz, 1H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 h
  2. extractionextracted with ethyl acetate (4×150 mL)
  3. washThe combined organic layer was washed with cold water (150 mL), brine (100 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto afford crude, which
  7. customwas purified by column chromatography over silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-91a8b6e7e13f41f6a15eb0157a78bef9
Source dataset
uspto-grants-2015_08
Patent number
US09114141B2

Reaction notes

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