Sodium hydride → HCID 68454724, compound

HRID 2355239Notes

Reaction equation

HRID 2355239 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)#[N:2].[H-].[Na+].[C:14]([O:18][C:19]([NH:21][C:22]([CH3:27])([CH3:26])[CH2:23][CH2:24]Cl)=[O:20])([CH3:17])([CH3:16])[CH3:15]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:14]([O:18][C:19]([NH:21][C:22]([CH3:26])([CH3:27])[CH2:23][CH2:24][N:8]1[C:9]2[C:5](=[CH:4][C:3]([C:1]#[N:2])=[CH:11][CH:10]=2)[CH:6]=[CH:7]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27513Indole-5-carbonitrileHCID 57429079tert-butyl N-(4-chloro-2-methylbutan-2-yl)carbamate

Product 1

HCID 68454724HCID 68454724, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Under a nitrogen atmosphere 4.07 g (16.9 mmol) 5-cyanoindole are dissolved in 30 ml DMF, and 0.73 g (18.3 mmol) sodium hydride (60% dispersion in mineral oil) are added batchwise while cooling with ice and with stirring. Then the mixture is stirred for 30 minutes at ambient temperature. It is heated to 50° C., 0.41 g (1.1 mmol) tetrabutylammonium iodide are added and over a period of 5 hours a solution of N-tert-butoxycarbonyl-3-chloro-1,1-dimethyl-propylamine is added dropwise. Then the mixture is stirred for 18 hours at ambient temperature. Then the reaction solution is poured onto water and extracted with ethyl acetate. The organic phases are combined, dried on sodium sulphate and freed from the solvent in vacuo. The residue is chromatographed on silica gel (petroleum ether/ethyl acetate=100:0→70:30). The product fractions are combined and freed from the solvent in vacuo. The residue is dissolved in 5 ml of methanol and poured onto 50 ml hot water. The precipitate thus obtained is suction filtered and dried in vacuo and reacted further without any further purification.

Workup

  1. temperaturewhile cooling with ice
  2. stirringThen the mixture is stirred for 30 minutes at ambient temperature
  3. additionis added dropwise
  4. stirringThen the mixture is stirred for 18 hours at ambient temperature
  5. additionThen the reaction solution is poured onto water
  6. extractionextracted with ethyl acetate
  7. customdried on sodium sulphate
  8. customThe residue is chromatographed on silica gel (petroleum ether/ethyl acetate=100:0→70:30)
  9. dissolutionThe residue is dissolved in 5 ml of methanol
  10. additionpoured onto 50 ml hot water
  11. customThe precipitate thus obtained
  12. filtrationfiltered
  13. customdried in vacuo
  14. customreacted further without any further purification

Sources & evidence

ORD record
ord-d6e6a7ba20394a339155b237c11c1604
Source dataset
uspto-grants-2010_07
Patent number
US07754756B2

Reaction notes

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