Triethylamine → Capravirine

HRID 8408Notes

Reaction equation

HRID 8408 reaction equation
[C:1]([O:4][CH2:5][C:6]1[N:7]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH:8]=[C:9]([CH:11]([CH3:13])[CH3:12])[N:10]=1)(=[O:3])[NH2:2].[Cl:21][C:22]1[CH:23]=[C:24]([S:29]Cl)[CH:25]=[C:26]([Cl:28])[CH:27]=1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C1(C)C=CC=CC=1.CO.O.C(OCC)(=O)C>[C:1]([O:4][CH2:5][C:6]1[N:7]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[C:8]([S:29][C:24]2[CH:25]=[C:26]([Cl:28])[CH:27]=[C:22]([Cl:21])[CH:23]=2)=[C:9]([CH:11]([CH3:13])[CH3:12])[N:10]=1)(=[O:3])[NH2:2]

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 101305733,5-Dichlorobenzenesulfenyl chloride2×HCID 154583322-Carbamoyloxymethyl-4-isopropyl-1-(pyridin-4-yl)methyl-1H-imidazole

Product 1

HCID 1783CapravirineYield 153.9%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent3×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

The compound (13) (250 mg, 0.91 mmol) was dissolved in N,N-dimethylformamide (4 ml). The solution was cooled down to −30° C. under nitrogen atmosphere. To the solution were added, alternately each four time, a solution of the compound (3) (77 mg, 0.36 mmol) in toluene (150 mg) and a solution of triethylamine (36 mg, 0.36 mg) in toluene (150 mg), and additionally added a solution of the compound (3) (77 mg, 0.36 mmol) in toluene (150 mg). The reaction mixture was stirred at −30° C. for 30 minutes, and ethyl acetate and aqueous sodium hydrogen carbonate were added thereto. The objective (14) was extracted into the ethyl acetate layer. Diluted aqueous hydrochloric acid was added to the ethyl acetate layer to transfer the objective compound into the aqueous layer. The aqueous solution was neutralized by aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give oily residue. The oily residue was dissolved in methanol (0.9 ml), and water (0.7 ml) was added dropwise thereto for 1–2 minutes at room temperature for crystallization. The suspension was stirred for 30 minutes at room temperature, additionally for 30 minutes under ice-cooling, filtered, washed with 50% aqueous methanol, and dried to yield the objective (14) (250 mg) as a white crystal. Yield 61%.

Workup

  1. additionTo the solution were added
  2. extractionThe objective (14) was extracted into the ethyl acetate layer
  3. additionDiluted aqueous hydrochloric acid was added to the ethyl acetate layer
  4. extractionextracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give oily residue
  8. customfor 1–2 minutes at room temperature for crystallization
  9. stirringThe suspension was stirred for 30 minutes at room temperature, additionally for 30 minutes under ice-
  10. temperaturecooling
  11. filtrationfiltered
  12. washwashed with 50% aqueous methanol
  13. customdried

Sources & evidence

ORD record
ord-3456253717b045689467d4c971aaa76f
Source dataset
uspto-grants-2006_08
Patent number
US07087764B2

Reaction notes

Loading…