Methyl 4-(bromomethyl)-3-methoxybenzoate → Methyl 4-[1-(2-carbamoylethyl)-5-(N-cyclopentylmethylcarbamoyl)indol-3-ylmethyl]-3-methoxybenzoate

HRID 728673

Reaction equation

HRID 728673 reaction equation
[C:1]([CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([C:15](=[O:23])[NH:16][CH2:17][CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)(=[O:3])[NH2:2].Br[CH2:25][C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][C:27]=1[O:36][CH3:37]>O1CCOCC1.C(OCC)(=O)C.[Ag-]=O>[C:1]([CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([C:15](=[O:23])[NH:16][CH2:17][CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:12][CH:13]=2)[C:8]([CH2:25][C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][C:27]=2[O:36][CH3:37])=[CH:7]1)(=[O:3])[NH2:2]

Participants

6

Reactant 2

HCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoateHCID 198224771-(2-carbamoylethyl)-5-(N-cyclopentylmethylcarbamoyl)indole

Product 1

HCID 19822473Methyl 4-[1-(2-carbamoylethyl)-5-(N-cyclopentylmethylcarbamoyl)indol-3-ylmethyl]-3-methoxybenzoateYield 39%

Reagents, catalysts & solvents 3

HCID 178418778HCID 178418778, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Silver(I) oxide (0.17 g) was added to a solution of 1-(2-carbamoylethyl)-5-(N-cyclopentylmethylcarbamoyl)indole (0.70 g) and methyl 4-bromomethyl-3-methoxybenzoate (B)(0.19 g) in 1,4-dioxane (10 ml). The mixture was protected from light and stirred at 80° C. under an atmosphere of nitrogen for 12 hours. The mixture was then diluted with 1:1 v/v ethyl acetate:ether (50 ml) and filtered. The filtrate was washed sequentially with water and brine, dried (MgSO4), and evaporated. The residual yellow gum was purified by flash chromatography on silica gel (500 ml), eluting with 5:95 v/v methanol:chloroform to give the title compound (0.14 g, 39%) as a white solid; mp 189°-191° C. (d); NMR (250 MHz, DMSO-d6): 1.2-1.8(broad m, 8H, cyclopentyl), 2.2(sep, 1H, cyclopentylmethine), 3.2(t, 2H, CH2NH), 7.2(m, 2H), 7.3(broad s, 1H, CONH2), 7.5 (m, 3H), 7.7(d, 1H, H6 -indole), 8.0(s, 1H, H4 -indole), 8.3(t, 1H, NHCO).

Workup

  1. filtrationether (50 ml) and filtered
  2. washThe filtrate was washed sequentially with water and brine
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe residual yellow gum was purified by flash chromatography on silica gel (500 ml)
  6. washeluting with 5:95 v/v methanol

Sources & evidence

ORD record
ord-52361734dd5344259ca8db06edd05715
Source dataset
uspto-grants-1991_09
Patent number
US05049679

Linked notes

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