Potassium Carbonate → 2-fluoro-N-(2-fluoro-3-[5-(2-methoxy-pyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-benzenesulfonamide

HRID 60094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 60094
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:30])=[C:15]([NH:19][S:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[F:29])(=[O:22])=[O:21])[CH:16]=[CH:17][CH:18]=3)=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:31][O:32][C:33]1[N:38]=[CH:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=1.C(=O)([O-])[O-].[K+].[K+]>[Pd].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.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(#N)C>[F:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[S:20]([NH:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:36]4[CH:35]=[N:34][C:33]([O:32][CH3:31])=[N:38][CH:37]=4)[CH:3]=3)[NH:8][CH:9]=2)=[O:12])[C:14]=1[F:30])(=[O:22])=[O:21]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 534405922-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidineHCID 58368734HCID 58368734, Verbindung

Produkt 1

HCID 583687582-fluoro-N-(2-fluoro-3-[5-(2-methoxy-pyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-benzenesulfonamideAusbeute 25,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

In a microwave vial, N-[3-(5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2-fluoro-phenyl]-2-fluoro-benzenesulfonamide (21, 100 mg, 0.203 mmol), 2-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidine (22, 72 mg, 0.305 mmol) and tetrakis-(triphenylphosphine) palladium(0) (10 mg) are combined with potassium carbonate (0.609 mL, 1M aqueous, 0.609 mmol) and 0.6 mL of acetonitrile. The reaction mixture is heated in a microwave at 160° C. for 15 minutes. The mixture is filtered through celite, and the celite is washed with water and ethyl acetate. The aqueous layer is separated from the filtrate and extracted with ethyl acetate. The organic portions are combined and washed with brine, then dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with methanol and dichloromethane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (P-1518, 27 mg). MS (ESI) [M+H+]+=521.95.

Aufarbeitung

  1. filtrationThe mixture is filtered through celite
  2. washthe celite is washed with water and ethyl acetate
  3. customThe aqueous layer is separated from the filtrate
  4. extractionextracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under vacuum
  9. customThe resulting material is purified by silica gel column chromatography
  10. washeluting with methanol and dichloromethane
  11. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-cd9cd68d9e844acc931889fd7116d154
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440969B2

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