Cesium carbonate → [7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(3-pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-amine

HRID 449221Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 449221
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH2:18])[N:16]=[N:17][C:12]=2[CH:11]=1.Br[C:23]1[CH:28]=[CH:27][C:26]([S:29]([CH2:32][CH2:33][CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)(=[O:31])=[O:30])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C(Cl)Cl.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH:18][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH2:32][CH2:33][CH2:34][N:35]4[CH2:36][CH2:37][CH2:38][CH2:39]4)(=[O:31])=[O:30])=[CH:25][CH:24]=3)[N:16]=[N:17][C:12]=2[CH:11]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 248227537-(2-Chloro-5-methoxyphenyl)-5-methylbenzo[e][1,2,4]triazin-3-amineHCID 529828661-(3-(4-Bromophenylsulfonyl)propyl)pyrrolidine

Produkt 1

HCID 59837755[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(3-pyrrolidin-1-yl-propane-1-sulfonyl)-phenyl]-amineAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a dry 25 mL round bottom flask, 7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.0361 g, 0.122 mmol, 1 equiv), 1-[3-(4-bromo-benzenesulfonyl)-propyl]-pyrrolidine (0.061 g, 0.184 mmol, 1.5 equiv), cesium carbonate (0.120 g, 0.367 mmol, 3 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethyl xanthene (0.014 g, 0.0244 mmol, 0.2 equiv) and tris(dibenzylideneacetone) dipalladium (0.012 g, 0.0122 mmol, 0.1 equiv) were combined. The reactants were flushed with argon, diluted with dioxane (6 mL) and outfitted with reflux condenser. The reaction was heated to reflux for 18 hours, filtered hot, diluted with ethyl acetate and washed with brine. The brine layer was back extracted once with fresh ethyl acetate. The organic phases were combined and dried over sodium sulfate (Na2SO4). Filtration followed by evaporation provided crude product, which was dissolved in minimum amount of DCM and precipitated out with excess hexanes. Solids were filtered off and dried to yield a yellow powder (0.06 g, 91% yield).

Aufarbeitung

  1. customThe reactants were flushed with argon
  2. additiondiluted with dioxane (6 mL)
  3. temperaturewith reflux condenser
  4. temperatureThe reaction was heated
  5. temperatureto reflux for 18 hours
  6. filtrationfiltered hot
  7. additiondiluted with ethyl acetate
  8. washwashed with brine
  9. extractionThe brine layer was back extracted once with fresh ethyl acetate
  10. dry with materialdried over sodium sulfate (Na2SO4)
  11. filtrationFiltration
  12. customfollowed by evaporation
  13. customprovided crude product, which
  14. customprecipitated out with excess hexanes
  15. filtrationSolids were filtered off
  16. customdried

Quellen und Nachweise

ORD-Eintrag
ord-8ee467da33a74c46b9c4ff36ac8f88a5
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481536B2

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