Cesium carbonate → N-[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]pentanamide

HRID 2089006

Reaktionsgleichung

Reaktionsgleichung von HRID 2089006
Cl[C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10](S(C3C=CC=CC=3)(=O)=O)[CH:9]=2)[CH:5]=[C:4]([Cl:26])[N:3]=1.[C:27]([NH2:33])(=[O:32])[CH2:28][CH2:29][CH2:30][CH3:31].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[OH-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:26][C:4]1[N:3]=[C:2]([NH:33][C:27](=[O:32])[CH2:28][CH2:29][CH2:30][CH3:31])[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH:5]=1

Komponenten

7

Edukt 5

HCID 10796Cesium carbonateHCID 12298PentanamideHCID 14798Sodium HydroxideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866498693-(2,6-dichloropyridin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

Produkt 1

HCID 49830337N-[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]pentanamideAusbeute 11,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 167845palladium(II) acetateKatalysator

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of Example 7a (82.5 mg, 0.204 mmol), pentanamide (28.9 mg, 0.286 mmol), cesium carbonate (100 mg, 0.306 mmol), palladium (II) acetate (2.29 mg, 10.2 μmol), and Xantphos (8.86 mg, 0.015 mmol) was degassed and heated at 85° C. in a sealed vial for 6 hours. The reaction mixture was cooled and concentrated. The residue was treated with 20% brine and extracted with EtOAc (2×). The organic layers were dried and concentrated. The crude intermediate was dissolved in dioxane (1.5 mL) and treated with 20% sodium hydroxide (0.15 mL, 0.20 mmol). The mixture was heated at 50° C. for 2 hours. The solvent was evaporated. The residue was treated with water, sonicated, filtered, and washed with water, and purified by reverse-phase HPLC as described in Example 56 to give the title compound (8.0 mg) as trifluoroacetic acid salts. 1H NMR (500 MHz, DMSO-d6) ppm 0.90 (t, J=7.48 Hz, 3H), 1.27-1.38 (m, 2H), 1.54-1.64 (m, 2H), 2.43 (t, J=7.32 Hz, 2H), 7.29 (m, 1H), 7.57 (s, 1H), 8.28-8.37 (m, 3H), 8.60 (s, 1H), 10.74 (s, 1H), 12.36 (s, 1H). MS (ESI+) m/z 328.9 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. additionThe residue was treated with 20% brine
  4. extractionextracted with EtOAc (2×)
  5. customThe organic layers were dried
  6. concentrationconcentrated
  7. dissolutionThe crude intermediate was dissolved in dioxane (1.5 mL)
  8. temperatureThe mixture was heated at 50° C. for 2 hours
  9. customThe solvent was evaporated
  10. additionThe residue was treated with water
  11. customsonicated
  12. filtrationfiltered
  13. washwashed with water
  14. custompurified by reverse-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-6be7c39664a3493d9c4486adf655f6f4
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08435980B2

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