1,2-Dichloroethane → 1-benzyl-5-hydroxy-2-methyl-1H-indole-3-carboxylic acid, 3,5-difluorobenzylamide

HRID 16627Notes

Reaction equation

HRID 16627 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[C:10]([C:18]([OH:20])=O)=[C:9]1[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[F:36][C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([F:45])[CH:44]=1)[CH2:40][NH2:41]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[F:36][C:37]1[CH:38]=[C:39]([CH:42]=[C:43]([F:45])[CH:44]=1)[CH2:40][NH:41][C:18]([C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=2)[N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9]=1[CH3:21])=[O:20]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 1452113,5-DifluorobenzylamineHCID 497872521-benzyl-5-hydroxy-2-methyl-1H-indole-3-carboxylic acid2×

Product 1

HCID 248041181-benzyl-5-hydroxy-2-methyl-1H-indole-3-carboxylic acid, 3,5-difluorobenzylamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-benzyl-5-hydroxy-2-methyl-1H-indole-3-carboxylic acid (Compound 2, 205 mg, 0.73 mmol) in CH2Cl2 (5 ml) and DMF (3 ml) was added EDC (211 mg, 1.1 mmol), HOBT (149 mg, 1.1 mmol) and 3,5-difluorobenzylamine (260 μl, 2.2 mmol). The mixture was stirred at room temperature for 16 h, diluted with EtOAc, and washed with 1M HCl, and brine, and dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (30% to 50% EtOAc-hexanes) to yield 1-benzyl-5-hydroxy-2-methyl-1H-indole-3-carboxylic acid, 3,5-difluorobenzylamide (Compound 3) as a beige solid.

Workup

  1. washwashed with 1M HCl, and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash column chromatography on silica gel (30% to 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-7a9e2327eeae4ef0891cfeb4d4e60298
Source dataset
uspto-grants-2010_06
Patent number
US07737173B2

Reaction notes

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