Sodium hydride → 4-{2-[1-Benzhydryl-5-chloro-2-(3-phenylmethanesulfonylamino-propyl)-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester

HRID 603956Notes

Reaction equation

HRID 603956 reaction equation
[C:1]1([CH2:7][S:8]([NH2:11])(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:14][O:15][C:16](=[O:53])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][C:26]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([Cl:35])[CH:33]=3)[N:28]([CH:36]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:27]=2[CH2:49][CH2:50][CH2:51]Br)=[CH:19][CH:18]=1>CN(C=O)C>[CH3:14][O:15][C:16](=[O:53])[C:17]1[CH:18]=[CH:19][C:20]([O:23][CH2:24][CH2:25][C:26]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([Cl:35])[CH:33]=3)[N:28]([CH:36]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:27]=2[CH2:49][CH2:50][CH2:51][NH:11][S:8]([CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)(=[O:9])=[O:10])=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 78318BenzenemethanesulfonamideHCID 161165974-{2-[1-Benzhydryl-2-(3-bromo-propyl)-5-chloro-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester

Product 1

HCID 161160774-{2-[1-Benzhydryl-5-chloro-2-(3-phenylmethanesulfonylamino-propyl)-1H-indol-3-yl]-ethoxy}-benzoic acid methyl esterYield 17.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

33.3 mg of α-toluene sulfonamide (0.0002M, 1.2 eq.) was dissolved in 0.5 mL of DMF and added to a slurry of 8.0 mg of 60% sodium hydride (0.0002M, 1.2 eq.) in 0.5 mL of DMF. The reaction was stirred for 30 min. at which point 100 mg of 4-{2-[1-Benzhydryl-2-(3-bromo-propyl)-5-chloro-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester (0.0002M, 1.0 eq.) in 0.5 mL of DMF was added and the solution was stirred for an additional 1 hour. The reaction was quenched with water and diluted with 10 mL of ethyl acetate. The organic layer was washed with water (2×5 mL) and brine (2×5 mL), dried over magnesium sulfate and evaporated to a yellow oil. The residue was purified via column chromatography (ethyl acetate/hexanes 5:95) to give 20 mg (17%) of 4-{2-[1-Benzhydryl-5-chloro-2-(3-phenylmethanesulfonylamino-propyl)-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester as a clear oil.

Workup

  1. additionwas added
  2. stirringthe solution was stirred for an additional 1 hour
  3. customThe reaction was quenched with water
  4. additiondiluted with 10 mL of ethyl acetate
  5. washThe organic layer was washed with water (2×5 mL) and brine (2×5 mL)
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to a yellow oil
  8. customThe residue was purified via column chromatography (ethyl acetate/hexanes 5:95)

Sources & evidence

ORD record
ord-3ce87ead7daf49d6b2b8b36fd10581dd
Source dataset
uspto-grants-2011_03
Patent number
US07906548B2

Reaction notes

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