Sodium hydride → HCID 69670891, compound

HRID 1191683Notes

Reaction equation

HRID 1191683 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[NH:8]2)=[CH:4][C:3]=1[O:17][CH3:18].[H-].[Na+].Br[CH2:22][C:23]1[S:24][CH:25]=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=1.[Cl-].[NH4+]>CN(C)C=O.ClCCl.CCCCCC>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:8]2[CH2:22][C:23]2[S:24][CH:25]=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=2)=[CH:4][C:3]=1[O:17][CH3:18]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 11043146Ethyl 2-(bromomethyl)-1,3-thiazole-4-carboxylateHCID 69096932HCID 69096932, compound

Product 1

HCID 69670891HCID 69670891, compoundYield 36.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21226440Methylenechloride HexaneSolvent

Procedure

To a solution of 6-fluoro-5-methoxy-2-phenylindole (200 mg) in N,N-dimethylformamide (4.1 mL) was added sodium hydride (dispersed in liquid paraffin, minimum 55%, 54 mg) under cooling with ice, and the mixture was stirred at room temperature for 70 minutes. Then a solution of ethyl 2-bromomethylthiazole-4-carboxylate (249 mg) in N,N-dimethylformamide (0.2 mL) was added, and the mixture was stirred at 80° C. for 25 hours. The reaction mixture was allowed to cool to ambient temperature. A saturated aqueous ammonium chloride solution-water (2/1) were added to the reaction mixture and this resulting mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (125 mg).

Workup

  1. temperatureunder cooling with ice
  2. stirringthe mixture was stirred at 80° C. for 25 hours
  3. temperatureto cool to ambient temperature
  4. extractionthis resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed successively with water and saturated saline
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a615bd7b96cc46deaff12d898257c13f
Source dataset
uspto-grants-2014_03
Patent number
US08680120B2

Reaction notes

Loading…