Acetonitrile → HCID 136052376, compound

HRID 1889476Notes

Reaction equation

HRID 1889476 reaction equation
[NH2:1][C:2]1[S:3][C:4]([CH2:11][CH3:12])=[CH:5][C:6]=1[C:7]([O:9]C)=O.ClC(Cl)(O[C:17](=[O:23])[O:18]C(Cl)(Cl)Cl)Cl.[NH2:25][C:26]1[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28]C=1.Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[C:48]2[N:52]=C(C(Cl)(Cl)Cl)O[N:49]=2)=[CH:38][CH:37]=1.[C:57](=[O:60])([O-])[O-].[K+].[K+].C(#[N:65])C>C(Cl)Cl.C(N(CC)CC)C>[CH2:11]([C:4]1[S:3][C:2]2[N:1]([CH2:35][C:36]3[CH:37]=[CH:38][C:39]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=4[C:48]4[NH:49][C:17](=[O:23])[O:18][N:52]=4)=[CH:40][CH:41]=3)[C:57](=[O:60])[N:65]([C:26]3[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][N:25]=3)[C:7](=[O:9])[C:6]=2[CH:5]=1)[CH3:12]

Participants

9

Reactant 6

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 133964-AminobenzonitrileHCID 94429TriphosgeneHCID 7370942-Amino-5-ethyl-3-thiophenecarboxylic acid methyl esterHCID 15290996HCID 15290996, compound

Product 1

HCID 136052376HCID 136052376, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution (40 mL) of methyl 2-amino-5-ethylthiophene-3-carboxylate (1 g) in methylene chloride were added triphosgene (0.69 g) and triethylamine (1.2 mL), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added 4-aminobenzonitrile (1.28 g), and the mixture was further stirred at room temperature for 1 hr, and the precipitated solid was collected by filtration. The obtained solid was dissolved in methanol (40 mL), sodium methoxide (0.73 g) was added, and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was neutralized with hydrochloric acid (10% methanol solution), and the precipitated solid was collected by filtration. The obtained to solid was dissolved in acetonitrile (50 mL), 3-[4′-(bromomethyl)biphenyl-2-yl]-5-(trichloromethyl)-1,2,4-oxadiazole (2.3 g) and potassium carbonate (1.5 g) were added, and the mixture was stirred at 50° C. for 2 hr. Insoluble material was filtered off, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography and dissolved in tetrahydrofuran (4 mL) and acetone (4 mL). 1N Aqueous sodium hydroxide solution (2 mL) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was adjusted to pH 7 with water and 1N hydrochloric acid, and extracted with chloroform. The obtained chloroform layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The precipitated solid was collected by filtration to give the title compound as colorless crystals (0.18 g, 6%).

Workup

  1. stirringthe mixture was further stirred at room temperature for 1 hr
  2. filtrationthe precipitated solid was collected by filtration
  3. dissolutionThe obtained solid was dissolved in methanol (40 mL)
  4. additionsodium methoxide (0.73 g) was added
  5. stirringthe mixture was stirred at 60° C. for 1 hr
  6. filtrationthe precipitated solid was collected by filtration
  7. customThe obtained to solid
  8. stirringthe mixture was stirred at 50° C. for 2 hr
  9. filtrationInsoluble material was filtered off
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography
  12. dissolutiondissolved in tetrahydrofuran (4 mL)
  13. addition1N Aqueous sodium hydroxide solution (2 mL) was added
  14. stirringthe mixture was stirred at room temperature for 1 hr
  15. extractionextracted with chloroform
  16. washThe obtained chloroform layer was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated under reduced pressure
  19. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-3704190a10e54a6cafcef4724d8b799b
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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