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

HRID 1069615Notes

Reaction equation

HRID 1069615 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>CN(C=O)C.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

7

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 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

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

Sources & evidence

ORD record
ord-88f7edf2c8dc49b3b263986f81b99444
Source dataset
uspto-grants-2001_06
Patent number
US06252084B1

Reaction notes

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