Sodium hydride → [3-(1-Benzyl-3-carbamoylmethyl-2-ethyl-1H-indol-5-yloxy)-propyl]-phosphonic acid dimethyl ester

HRID 2292799Notes

Reaction equation

HRID 2292799 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([CH2:18][CH3:19])=[C:5]2[CH2:20][C:21]([NH2:23])=[O:22].[H-].[Na+].[CH3:26][O:27][P:28]([CH2:32][CH2:33][CH2:34]Br)(=[O:31])[O:29][CH3:30].CO.CCOC(C)=O>O>[CH3:26][O:27][P:28]([CH2:32][CH2:33][CH2:34][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([CH2:18][CH3:19])=[C:5]2[CH2:20][C:21]([NH2:23])=[O:22])(=[O:31])[O:29][CH3:30]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 2834991-Bromo-3-dimethoxyphosphorylpropaneHCID 105428362-ethyl-5-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamideHCID 21584119Ethylacetate methanol

Product 1

HCID 10504075[3-(1-Benzyl-3-carbamoylmethyl-2-ethyl-1H-indol-5-yloxy)-propyl]-phosphonic acid dimethyl esterYield 69%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5-Hydroxy-2-ethyl-1-(phenylmethyl)-1H-indole-3-acetamide (308 mg, 1.0 mmol) was added to 40 mg (1.0 mmol) of NaH/mineral oil washed with hexanes) in 4 mL of DMF, stirred 0.5 hours, 196 mg (0.85 mmol) of (3-bromopropyl)phosphonic acid dimethyl ester added and stirring maintained for 6.5 hours. The mixture was diluted with water, extracted with ethyl acetate, the ethyl acetate washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed on silica gel eluting with EtOAc, 5% MeOH/EtOAc, then 10% MeOH/EtOAc to give 269 mg (59% yield) of [3-[[3-(2-amino-2-oxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester.

Workup

  1. washwashed with hexanes) in 4 mL of DMF
  2. stirringstirring
  3. temperaturemaintained for 6.5 hours
  4. extractionextracted with ethyl acetate
  5. washthe ethyl acetate washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel eluting with EtOAc, 5% MeOH/EtOAc

Sources & evidence

ORD record
ord-1977ada595c9498a8f22bfd82ab99c35
Source dataset
uspto-grants-1997_11
Patent number
US05684034

Reaction notes

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