Methyl iodide → Methyl 4-[5-(N-cyclopentylmethylcarbamoyl)-1-methylindol-3-ylmethyl]-3-methoxybenzoate

HRID 728601Notes

Reaction equation

HRID 728601 reaction equation
[CH:1]1([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH:14]=[C:13]3[CH2:19][C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]=2[O:30][CH3:31])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].I[CH3:35]>CN(C)C=O>[CH:1]1([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:35])[CH:14]=[C:13]3[CH2:19][C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]=2[O:30][CH3:31])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10070759methyl 4-[5-(N-cyclopentylmethylcarbamoyl)indol-3-ylmethyl]-3-methoxybenzoate

Product 1

HCID 10071602Methyl 4-[5-(N-cyclopentylmethylcarbamoyl)-1-methylindol-3-ylmethyl]-3-methoxybenzoateYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of methyl 4-[5-(N-cyclopentylmethylcarbamoyl)indol-3-ylmethyl]-3-methoxybenzoate (C) (1.52 g) in N,N-dimethylformamide (5 ml) was added to a slurry of sodium hydride (0.088 g) in N,N-dimethylformamide (3 ml) at 0° C. The mixture was stirred under a nitrogen atmosphere for 20 minutes at 0° C. and for 15 minutes at 25°0 C. The reaction was cooled to 0° C., treated with a cold solution of iodomethane (0.57 g) in N,N-dimethylformamide (2 ml), and then allowed to warm to 25°. The mixture was recooled to 0°, quenched with saturated aqueous ammonium chloride, and evaporated. The residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4), and evaporated. The amber residue was purified by flash chromatography on silica gel (500 ml), eluting with 1:9 v/v ethyl acetate:chloroform, to yield the title compound (0.86 g, 55%) as a white foam; partial NMR (80 MHz, CDCl 3): 3.4(dd, 2H, CH2N), 3.73(s, 3H, NCH3), 3.89(s, 3H, OCH3), 3.92(s, 3H, OCH3), 4.12(s, 2H, ArCH2), 6.11(t, 1H, NH), 6.8(s, 1H, H2 -indole), 8.00(br s, 1H, H4 -indole).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. temperatureto warm to 25°
  3. customwas recooled to 0°
  4. customquenched with saturated aqueous ammonium chloride
  5. customevaporated
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. washwashed with water and brine
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe amber residue was purified by flash chromatography on silica gel (500 ml)
  11. washeluting with 1:9 v/v ethyl acetate

Sources & evidence

ORD record
ord-aad2a1bc73414735ac884248686fb426
Source dataset
uspto-grants-1991_09
Patent number
US05049576

Reaction notes

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