1,4-Dibromobutane → 8-(4-fluorophenyl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro-4H-1,3,3a,8-tetraazaazulene

HRID 546731Notes

Reaction equation

HRID 546731 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[NH:15][C:14](/[CH:16]=[CH:17]/[C:18]3[CH:23]=[CH:22][C:21]([N:24]4[CH:28]=[C:27]([CH3:29])[N:26]=[CH:25]4)=[C:20]([O:30][CH3:31])[CH:19]=3)=[N:13][N:12]=2)=[CH:6][CH:5]=1.Br[CH2:33][CH2:34][CH2:35][CH2:36]Br.[Cl-].[NH4+]>CN(C=O)C>[F:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:11]3[N:12]([N:13]=[C:14](/[CH:16]=[CH:17]/[C:18]4[CH:23]=[CH:22][C:21]([N:24]5[CH:28]=[C:27]([CH3:29])[N:26]=[CH:25]5)=[C:20]([O:30][CH3:31])[CH:19]=4)[N:15]=3)[CH2:36][CH2:35][CH2:34][CH2:33]2)=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 80561,4-DibromobutaneHCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 178489930HCID 178489930, compound

Product 1

HCID 576092628-(4-fluorophenyl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro-4H-1,3,3a,8-tetraazaazulene

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

60% sodium hydride (10 mg) was added to a solution of (4-fluorophenyl)-{5-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-4H-[1,2,4]triazol-3-yl}amine synthesized in Example 162 (47.5 mg) in DMF (3 mL) at room temperature, and the reaction solution was stirred at room temperature for 10 minutes. 1,4-Dibromobutane (0.02 mL) was added to the reaction solution at room temperature, and the reaction solution was stirred at room temperature for two hours. 60% sodium hydride (5 mg) was added to the reaction solution at room temperature, and the reaction solution was stirred at room temperature for two hours. A saturated ammonium chloride solution was added to the reaction solution at 0° C., followed by extraction with ethyl acetate. The resulting extract was washed with a saturated sodium bicarbonate solution and a saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system, then ethyl acetate-methanol system), silica gel column chromatography (elution solvent: heptane-ethyl acetate system, then ethyl acetate-methanol system) and CHIRALPAK™ IA manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: ethanol) to obtain 14 mg of the title compound. The property values of the compound are as follows.

Workup

  1. stirringthe reaction solution was stirred at room temperature for two hours
  2. stirringthe reaction solution was stirred at room temperature for two hours
  3. extractionfollowed by extraction with ethyl acetate
  4. extractionThe resulting extract
  5. washwas washed with a saturated sodium bicarbonate solution
  6. dry with materialThe resulting organic layer was dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (carrier
  9. washelution solvent
  10. washheptane-ethyl acetate system, then ethyl acetate-methanol system), silica gel column chromatography (elution solvent

Sources & evidence

ORD record
ord-b1bc66f10de04f88b823cc44a07031e1
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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