Imidazole → HCID 86708064, compound

HRID 1524361Notes

Reaction equation

HRID 1524361 reaction equation
CS(O[CH2:6][C:7]([F:45])([F:44])[CH2:8][CH2:9][C@H:10]([N:20]([S:26]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])=[CH:31][CH:30]=1)(=[O:28])=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:11][O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])(=O)=O.[N-:46]=[N+:47]=[N-:48].[Na+].C1OCCOCCOCCOCCOCCOC1.N1C=CN=C1.[Si](Cl)(C(C)(C)C)(C)C>CS(C)=O.CN(C1C=CN=CC=1)C.O>[N:46]([CH2:6][C:7]([F:45])([F:44])[CH2:8][CH2:9][C@H:10]([N:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[S:26]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])=[CH:31][CH:30]=1)(=[O:28])=[O:27])[CH2:11][O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[N+:47]=[N-:48]

Participants

9

Reactant 5

HCID 795ImidazoleHCID 2855718-Crown-6HCID 28928tert-Butyldimethylsilyl chlorideHCID 33557Sodium AzideHCID 86708063HCID 86708063, compound

Product 1

HCID 86708064HCID 86708064, compoundYield 38.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
125 °C

Procedure

To a stirred solution of the material from Step 8 (167 mg, 0.233 mmol) in DMSO (2.3 mL) were added sodium azide (23 mg, 0.35 mmol) and 18-crown-6 (3 mg, 0.012 mmol). The reaction mixture was stirred at 125° C. for 24 hours. Upon cooling to room temperature, the reaction mixture was concentrated to dryness in vacuo. LCMS showed that TBS group was removed. The residue was dissolved in dichloromethane (2.3 mL). Imidazole (32 mg, 0.465 mmol), DMAP (1 mg, 0.008 mmol) and TBS—Cl (70 mg, 0.465 mmol) were added. The reaction mixture was stirred at room temperature overnight, poured into water and extracted with dichloromethane (2×). The combined organics were washed with 1 N HCl, saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using EtOAc-hexanes to afford 60 mg of the title compound.

Workup

  1. temperatureUpon cooling to room temperature
  2. concentrationthe reaction mixture was concentrated to dryness in vacuo
  3. customwas removed
  4. dissolutionThe residue was dissolved in dichloromethane (2.3 mL)
  5. stirringThe reaction mixture was stirred at room temperature overnight
  6. extractionextracted with dichloromethane (2×)
  7. washThe combined organics were washed with 1 N HCl, saturated aqueous NaHCO3 and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-18729d82e905489d8bbad4fabc828fbd
Source dataset
uspto-grants-2015_07
Patent number
US09079834B2

Reaction notes

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