Benzophenone imine → (S)-tert-butyl 3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate

HRID 516187Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516187
Cl[C:2]1[C:7]2[C:8]([C:23]#[C:24][C:25]3[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[C:27]([O:33][CH3:34])[CH:26]=3)=[CH:9][N:10]([C@H:11]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]3)[C:6]=2[CH:5]=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].C(=[NH:54])(C1C=CC=CC=1)C1C=CC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:54][C:2]1[C:7]2[C:8]([C:23]#[C:24][C:25]3[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[C:27]([O:33][CH3:34])[CH:26]=3)=[CH:9][N:10]([C@H:11]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]3)[C:6]=2[CH:5]=[CH:4][N:3]=1

Komponenten

6

Edukt 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 89870976(S)-tert-butyl 3-(4-chloro-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate

Produkt 1

HCID 89871097(S)-tert-butyl 3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
115 °C

Versuchsvorschrift

Under a nitrogen atmosphere, the (S)-tert-butyl 3-(4-chloro-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate (120 mg) obtained in Step 3,2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP) (26 mg), sodium tert-butoxide (72 mg), benzophenone imine (92 mg), and tris(dibenzylideneacetone)dipalladium (36 mg) were suspended in toluene (10 ml), and the result was stirred at 115° C. for 90 minutes. After dilution with ethyl acetate, celite filtration was performed. The solvent was distilled off under reduced pressure. Hydroxyaminehydrochloride (366 mg), sodium bicarbonate (442 mg), methanol (16 ml), and water (4 ml) were added to the resulting residue, and the resulting mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure. Thereafter, ethyl acetate and a saturated sodium chloride solution were added to separate the organic layer. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a colorless, amorphous substance (35 mg). Physical properties: m/z [M+H]+ 463.4

Aufarbeitung

  1. filtrationAfter dilution with ethyl acetate, celite filtration
  2. distillationThe solvent was distilled off under reduced pressure
  3. additionHydroxyaminehydrochloride (366 mg), sodium bicarbonate (442 mg), methanol (16 ml), and water (4 ml) were added to the resulting residue
  4. stirringthe resulting mixture was stirred at room temperature for 2 hours
  5. distillationThe solvent was distilled off under reduced pressure
  6. additionThereafter, ethyl acetate and a saturated sodium chloride solution were added
  7. customto separate the organic layer
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-a3a30776979f43da93bcc36f64575c62
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108973B2

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