Dimethylformamide → [3-[[3-(2-amino-2-oxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester

HRID 1069645Notes

Reaction equation

HRID 1069645 reaction equation
[CH:1]1([C:4]2[N:5]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:6]3[C:11]([C:12]=2[CH2:13][C:14]([NH2:16])=[O:15])=[CH:10][C:9]([OH:17])=[CH:8][CH:7]=3)[CH2:3][CH2:2]1.CN(C=O)C.[H-].[Na+].[CH3:32][O:33][P:34]([CH2:38][CH2:39][CH2:40]Br)(=[O:37])[O:35][CH3:36]>C1COCC1.O.C(OCC)(=O)C>[CH3:32][O:33][P:34]([CH2:38][CH2:39][CH2:40][O:17][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]([CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:4]([CH:1]1[CH2:2][CH2:3]1)=[C:12]2[CH2:13][C:14]([NH2:16])=[O:15])(=[O:37])[O:35][CH3:36]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2834991-Bromo-3-dimethoxyphosphorylpropaneHCID 106635022-cyclopropyl-5-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamide

Product 1

HCID 10600435[3-[[3-(2-amino-2-oxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl esterYield 71%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Cyclopropyl-5-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamide (295 mg. 0.9 mmol) was dissolved in 10 mL of THF and 40 mL of DMF and 45 mg (1.1 mmol) of 60% NaH/mineral oil added. After 0.17 hours, 250 mg (1.1 mmol) of (3-bromopropyl)phosphonic acid dimethyl ester was added and stirring maintained for 6.5 hours. The mixture was diluted with water and ethyl acetate, the organic layer separated, washed with water, brine and dried (Na2SO4). The solution was evaporated at reduced pressure and the residue chromatographed on silica gel eluting with a gradient, 1% MeOH/methylene chloride→5% MeOH/methylene chloride, to give 280 mg (71% yield) of [3-[[3-(2-amino-2-oxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester.

Workup

  1. temperaturemaintained for 6.5 hours
  2. customthe organic layer separated
  3. washwashed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customThe solution was evaporated at reduced pressure
  6. customthe residue chromatographed on silica gel eluting with a gradient, 1% MeOH/methylene chloride→5% MeOH/methylene chloride

Sources & evidence

ORD record
ord-b86e293402604d4a83c07c5e5422e1d6
Source dataset
uspto-grants-2001_06
Patent number
US06252084B1

Reaction notes

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