Dimethyl Sulfoxide → 6-(Phenylethynyl)-1-(propane-2-sulfonyl)-1H-benzimidazol-2-amine

HRID 2252025Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2252025
[CH:1]([S:4]([N:7]1[C:11]2[CH:12]=[C:13](I)[CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH2:17])(=[O:6])=[O:5])([CH3:3])[CH3:2].CS(C)=O.C(N(CC)CC)C.[C:29]1([C:35]#[CH:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CC#N.C([O-])(=O)C.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(=O)C.[Cu]I>[CH:1]([S:4]([N:7]1[C:11]2[CH:12]=[C:13]([C:36]#[C:35][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH2:17])(=[O:6])=[O:5])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 106425631-Isopropylsulfonyl-2-amino-6-iodobenzimidazole

Produkt 1

HCID 179817066-(Phenylethynyl)-1-(propane-2-sulfonyl)-1H-benzimidazol-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 84538Bis(triphenylphosphinepalladium) acetateKatalysatorHCID 6342AcetonitrileLösungsmittel2×

Reaktionsbedingungen

Temperatur
22.5 °C

Versuchsvorschrift

Under a nitrogen atmosphere, combine 1-isopropylsulfonyl-2-amino-6-iodo benzimidazole (400 g, 1.095 moles), bis(triphenylphosphine) palladium(II)acetate (32.8 g, 0.044 moles), and CuI (41.7 g, 0.219 moles), followed by DMSO (8.4 L) and triethylamine (317 g, 3.133 moles). Stir the resulting mixture at 20 to 25° C. for 15 minutes, followed by the addition of phenylacetylene (168 g, 1.645 moles) over 30 minutes giving a temperature rise to 34° C. Cool the reaction slowly to 20 to 25° C., and after 15 hours, quench an aliquot of the reaction into water and dilute with CH3CN for HPLC analysis. The HPLC chromatogram (Column:Zorbax SB-C8, 4.6×250 mm, 5 micron UV=218 nm, gradients acetonitrile/buffer) indicates complete consumption of the iodide with the production of two new less polar products (desired product and phenylacetylene dimer). Add water (4 L) to the reaction over 1 hour giving a temperature rise to 40° C., and a dark precipitate (mainly catalyst). Filter the reaction through a thin layer of Celite® (24 cm diameter) with no washing of the catalyst waste cake. Return the filtrate to the reactor and add an additional 4 L of water over 1 hour to give an ending temperature of 45° C., and a yellow slurry. Leave the mixture to cool overnight to 20 to 25° C. with stirring. Collect the solids by vacuum filtration, and wash with water (4 L). Dry the solids at 60° C. under vacuum to constant weight. Yield=319 g (86%) of light yellow granular solid. MS(ES+): m/z=340.2 (M+H)+

Aufarbeitung

  1. customgiving a temperature rise to 34° C
  2. temperatureCool
  3. customthe reaction slowly to 20 to 25° C.
  4. waitafter 15 hours
  5. customquench
  6. customan aliquot of the reaction into water
  7. customconsumption of the iodide with the production of two new less polar products (desired product and phenylacetylene dimer)
  8. customAdd water (4 L) to the reaction over 1 hour
  9. customgiving a temperature rise to 40° C.
  10. filtrationFilter
  11. customthe reaction through a thin layer of Celite® (24 cm diameter) with
  12. washno washing of the catalyst waste cake
  13. additionadd an additional 4 L of water over 1 hour
  14. customto give an ending temperature of 45° C.
  15. customLeave the mixture
  16. temperatureto cool overnight to 20 to 25° C.
  17. stirringwith stirring
  18. customCollect the solids
  19. filtrationby vacuum filtration
  20. washwash with water (4 L)
  21. customDry the solids at 60° C. under vacuum to constant weight

Quellen und Nachweise

ORD-Eintrag
ord-dd2e3208c5f042e4999ca1aeadb7339f
Quelldatensatz
uspto-grants-2008_01
Patentnummer
US07320995B2

Notizen zur Reaktion

Wird geladen…