(2-Bromoethyl)cyclohexane → HCID 178473476, compound

HRID 1110845Notes

Reaction equation

HRID 1110845 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:13])[O:10][CH2:11][CH3:12])[N:5]=[C:4]2[NH:14][CH:15]=[N:16][C:3]=12.[H-].[Na+].ClCOCC1C=CC=CC=1.ClC1C=C(NC(=O)OCC)N=C2N(COCC3C=CC=CC=3)C=NC=12.ClC1C=C(NC(=O)OCC)N=C2N=CN(COCC3C=CC=CC=3)C=12.[CH:79]1([CH2:85][CH2:86]Br)[CH2:84][CH2:83][CH2:82][CH2:81][CH2:80]1>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([N:8]([CH2:86][CH2:85][CH:79]2[CH2:84][CH2:83][CH2:82][CH2:81][CH2:80]2)[C:9](=[O:13])[O:10][CH2:11][CH3:12])[N:5]=[C:4]2[NH:14][CH:15]=[N:16][C:3]=12

Participants

8

Reactant 6

HCID 15440(2-Bromoethyl)cyclohexaneHCID 24758Sodium hydride2×HCID 137983Benzyl chloromethyl etherHCID 22154026HCID 22154026, compoundHCID 22154037HCID 22154037, compoundHCID 178473434HCID 178473434, compound

Product 1

HCID 178473476HCID 178473476, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 124 mg of ethyl N-(7-chloro-3H-imidazo[4,5-b]pyridin-5-yl)-carbamate in 2 ml of dry dimethylformamide is added 50 mg of sodium hydride (60% dispersion in mineral oil). After stirring for 10 minutes, 0.11 ml of benzyl chloromethyl ether is added, and the reaction is stirred for 3 hours. The reaction is quenched with water and extracted 3 times with ethyl acetate. The organic extract is washed with water, and dried (sodium sulfate). Evaporation of the solvents in vacuo leaves a residue which is purified by flash chromatography on silica gel (ether) to give a mixture of ethyl N-[7-chloro-3-(benzyloxymethyl)-3H-imidazo[4,5-b]pyridin-5-yl]-carbamate and ethyl N-[7-chloro-1-(benzyloxymethyl)-1H-imidazo[4,5-b]pyridin-5-yl]carbamate. To a solution of 100 mg of this mixture in 2 ml of dry dimethylformamide is added 17 mg of sodium hydride (60% dispersion in mineral oil) and 210 mg of 2-cyclohexylethyl bromide. The mixture is heated at 70° for 5 hours, cooled to room temperature, and quenched with water. The mixture is extracted 3 times with ethyl acetate. The organic extract is washed with water, and dried (sodium sulfate). The solvents are evaporated in vacuo, and the residue is then dissolved in 2 ml of ethanol. To this solution is added 0.1 ml of concentrated HCl, and the reaction is heated to 70° for 5 hours. After cooling to room temperature, the reaction is neutralized with saturated aqueous sodium bicarbonate, and extracted 3 times with methylene chloride. The combined organic extracts are dried (sodium sulfate) and the solvents evaporated in vacuo to give a residue which is purified by flash chromatography on silica gel (5% methanol/methylene chloride) to give ethyl N-(7-chloro-3H-imidazo[4,5-b]pyridin-5-yl)-N-(2-cyclohexylethyl)-carbamate.

Workup

  1. stirringthe reaction is stirred for 3 hours
  2. customThe reaction is quenched with water
  3. extractionextracted 3 times with ethyl acetate
  4. extractionThe organic extract
  5. washis washed with water
  6. dry with materialdried (sodium sulfate)
  7. customEvaporation of the solvents in vacuo
  8. customleaves a residue which
  9. customis purified by flash chromatography on silica gel (ether)
  10. customto give
  11. temperatureThe mixture is heated at 70° for 5 hours
  12. customquenched with water
  13. extractionThe mixture is extracted 3 times with ethyl acetate
  14. extractionThe organic extract
  15. washis washed with water
  16. dry with materialdried (sodium sulfate)
  17. customThe solvents are evaporated in vacuo
  18. dissolutionthe residue is then dissolved in 2 ml of ethanol
  19. additionTo this solution is added 0.1 ml of concentrated HCl
  20. temperaturethe reaction is heated to 70° for 5 hours
  21. temperatureAfter cooling to room temperature
  22. extractionextracted 3 times with methylene chloride
  23. dry with materialThe combined organic extracts are dried (sodium sulfate)
  24. customthe solvents evaporated in vacuo
  25. customto give a residue which
  26. customis purified by flash chromatography on silica gel (5% methanol/methylene chloride)

Sources & evidence

ORD record
ord-e7d6568dcddc42719ee0663586abae0a
Source dataset
uspto-grants-1990_12
Patent number
US04977144

Reaction notes

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