Sodium hydride → HCID 76282126, compound

HRID 929819Notes

Reaction equation

HRID 929819 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:25]=[C:24]([C:26]([NH2:28])=[O:27])[O:23][N:22]=2)=[CH:17][CH:16]=1>C1COCC1>[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[CH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:25]=[C:24]([C:26]([NH2:28])=[O:27])[O:23][N:22]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 852824-MethylindoleHCID 902024601613166-38-32×

Product 1

HCID 76282126HCID 76282126, compoundYield 14.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 4-methylindole (20 mg, 0.15 mmol) in THF (1 mL) was added NaH (60% dispersion; 5 mg, 0.125 mmol). The mixture was stirred for 30 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; 35 mg, 0.125 mmol) in THF (1 mL) was added. The reaction mixture was stirred at room temperature overnight. The THF was evaporated and the residue was taken up in DMF (2 mL). The reaction mixture was stirred at room temperature for 8 days, then 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 (16-20% acetone/CH2Cl2) to give 3-[4-(4-methyl-indol-1-ylmethyl)-phenyl]-isoxazole-5-carboxylic acid amide (6 mg, 14%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.35 (br. s., 1H), 7.97 (br. s., 1H), 7.81 (d, J=8.2 Hz, 2H), 7.43-7.56 (m, 2H), 7.17-7.34 (m, 3H), 6.91-7.03 (m, 1H), 6.80 (d, J=6.9 Hz, 1H), 6.51 (d, J=3.0 Hz, 1H), 5.47 (s, 2H), 2.45 (s, 2H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customThe THF was evaporated
  3. stirringThe reaction mixture was stirred at room temperature for 8 days
  4. additionH2O was added
  5. extractionthe mixture was extracted with EtOAc (3×25 mL)
  6. washThe combined organic layers were washed three times with H2O/brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. custompurified by chromatography (16-20% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-62554bcd994847ff9e839e95abb6d38d
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

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