Indole → HCID 74763828, compound

HRID 929814Notes

Reaction equation

HRID 929814 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].Br[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:24]=[C:23]([C:25]([NH2:27])=[O:26])[O:22][N:21]=2)=[CH:16][CH:15]=1.O>CN(C=O)C>[N:1]1([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:24]=[C:23]([C:25]([NH2:27])=[O:26])[O:22][N:21]=3)=[CH:18][CH:19]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

6

Reactant 4

HCID 798IndoleHCID 962WaterHCID 24758Sodium hydrideHCID 902024601613166-38-32×

Product 1

HCID 74763828HCID 74763828, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of indole (13 mg, 0.11 mmol) in DMF (1 mL) was added NaH (60% dispersion; 5 mg, 0.125 mmol). The mixture was stirred for 20 min and then a solution of 3-(4-bromomethyl-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 14; 30 mg, 0.107 mmol) in DMF (1 mL) was added. The reaction mixture was stirred at room temperature overnight. H2O was added and the mixture was extracted with EtOAc (3×25 mL). The combined organic layers were washed three times with H2O/brine, dried (Na2SO4), evaporated, and purified by chromatography (10-25% acetone/CH2Cl2) to give 3-(4-indol-1-ylmethyl-phenyl)-isoxazole-5-carboxylic acid amide (6 mg, 18%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.34 (br. s., 1H), 7.97 (br. s., 1H), 7.82 (d, J=8.2 Hz, 2H), 7.48-7.61 (m, 3H), 7.43 (d, J=7.8 Hz, 1H), 7.30 (d, J=8.2 Hz, 2H), 6.94-7.14 (m, 2H), 6.49 (d, J=3.0 Hz, 1H), 5.49 (s, 2H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with EtOAc (3×25 mL)
  3. washThe combined organic layers were washed three times with H2O/brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. custompurified by chromatography (10-25% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-4c308fac093b4c449cb7b50cf94f6a4a
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

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