Imidazole → (3R)-6-cyclohexyl-N-hydroxy-3-[3-(4-pyridinylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide

HRID 1279801Notes

Reaction equation

HRID 1279801 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[N:16]=2)[CH2:11][C:12](O)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.C[Si](C)(C)[O:41][NH2:42].N1C=CN=C1>ClCCl.C(OCC)(=O)C.CO>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([CH2:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[N:16]=2)[CH2:11][C:12]([NH:42][OH:41])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 682631,1'-CarbonyldiimidazoleHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 16747827HCID 16747827, compound

Product 1

HCID 16749000(3R)-6-cyclohexyl-N-hydroxy-3-[3-(4-pyridinylmethyl)-1,2,4-oxadiazol-5-yl]hexanamideYield 35.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (3R)-6-cyclohexyl-3-[3-(4-pyridinylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 106) (380 mg, 0.96 mmol) in dichloromethane (10 ml) was treated with 1,1′-carbonyldiimidazole (156 mg, 0.96 mmol) and stirred under a nitrogen atmosphere for 1 hour. O-(Trimethylsilyl)hydroxylamine (388 μl, 2.89 mmol) was added and the mixture was stirred for 3.5 hours. The mixture was then treated with methanol (5 ml) and stirred at room temperature for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with 95:5 (dichloromethane:methanol) to afford a white solid. Analysis suggests that 10% imidazole remains. The solid was dissolved in ethyl acetate and washed with water, dried over anhydrous magnesium sulphate, filtered and the solvent was removed under reduced pressure to afford the title compound as a white solid (128 mg).

Workup

  1. stirringthe mixture was stirred for 3.5 hours
  2. stirringstirred at room temperature for 2 hours
  3. customThe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with 95:5 (dichloromethane:methanol)
  10. customto afford a white solid
  11. washwashed with water
  12. dry with materialdried over anhydrous magnesium sulphate
  13. filtrationfiltered
  14. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8567d5fbe36547538740a08afe1e451f
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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