Imidazole → 2-{3,5-bis[(4-fluorobenzyl)oxy]phenyl}-N-(3-thioxo-3H-1,2,4-dithiazol-5-yl)acetoamide

HRID 1393857Notes

Reaction equation

HRID 1393857 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][O:7][C:8]2[CH:9]=[C:10]([CH2:23][C:24](O)=[O:25])[CH:11]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.N1C=CN=C1.[H-].[Na+].[NH2:48][C:49]1[S:50][S:51][C:52](=[S:54])[N:53]=1.O.[Cl-].[NH4+]>O1CCCC1>[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][O:7][C:8]2[CH:9]=[C:10]([CH2:23][C:24]([NH:48][C:49]3[S:50][S:51][C:52](=[S:54])[N:53]=3)=[O:25])[CH:11]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 795Imidazole2×HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 2735329Xanthane hydrideHCID 57429219Ammonium chloride monohydrateHCID 693066292-{3,5-Bis[(4-fluorobenzyl)oxy]phenyl}acetic acid

Product 1

HCID 596805122-{3,5-bis[(4-fluorobenzyl)oxy]phenyl}-N-(3-thioxo-3H-1,2,4-dithiazol-5-yl)acetoamideYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2-{3,5-Bis[(4-fluorobenzyl)oxy]phenyl}acetic acid (1.00 g, 2.60 mmol) was dissolved in tetrahydrofuran (9 ml), and 1,1′-carbonyldiimidazole (0.506 g, 3.12 mmol) was added thereto. The imidazole mixture was stirred for 1 hour at room temperature. Sodium hydride (60% oil suspension 0.104 g, 2.60 mmol) was suspended in tetrahydrofuran (9 ml), and 3-amino-1,2,4-dithiazole-5-thione (0.391 g, 2.60 mmol) was added thereto. After being stirred for 30 minutes at 0° C., the reaction mixture, with the imidazole mixture added thereto, was stirred for 7 hours at room temperature. The reaction mixture, with saturated ammonium chloride water added thereto, was extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate water and saturated brine successively, dried over MgSO4, and then concentrated. The obtained residue was purified by silica gel column chromatography (chloroform), to give 2-{3,5-bis[(4-fluorobenzyl)oxy]phenyl}-N-(3-thioxo-3H-1,2,4-dithiazol-5-yl)acetoamide (Compound 9) (0.292 g, 22%).

Workup

  1. stirringwas stirred for 7 hours at room temperature
  2. extractionwas extracted with ethyl acetate
  3. washThe organic layer was washed with saturated sodium bicarbonate water and saturated brine successively
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe obtained residue was purified by silica gel column chromatography (chloroform)

Sources & evidence

ORD record
ord-faef3cb1545247d599f6d59348916aa5
Source dataset
uspto-grants-2008_03
Patent number
US07348017B2

Reaction notes

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