Cesium carbonate → HCID 86709760, Verbindung

HRID 1529273Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529273
C([O-])([O-])=O.[Cs+].[Cs+].Br[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[N:12]=[C:11]2[C:23]1[N:28]=[C:27]([O:29][C@@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)[CH:26]=[N:25][CH:24]=1.[CH:43]([O:46][C:47]1[CH:52]=[N:51][CH:50]=[C:49](B2OC(C)(C)C(C)(C)O2)[N:48]=1)([CH3:45])[CH3:44]>Cl[Cu].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:44][CH:43]([O:46][C:47]1[N:48]=[C:49]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[N:12]=[C:11]3[C:23]2[N:28]=[C:27]([O:29][C@@H:30]3[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])[CH2:31]3)[CH:26]=[N:25][CH:24]=2)[CH:50]=[N:51][CH:52]=1)[CH3:45]

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 45786233HCID 45786233, VerbindungHCID 67960228(3R)-tert-butyl 3-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate

Produkt 1

HCID 86709760HCID 86709760, VerbindungAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 62652Cuprous chlorideKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Katalysator

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a 50 mL round bottom flask was added CuCl (0.035 g, 0.36 mmol), Cs2CO3 (0.467 g, 1.43 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.020 g, 0.04 mmol), tert-butyl (3R)-3-((6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate 10a (0.200 g, 0.36 mmol), Pd(OAc)2 (4.02 mg, 0.02 mmol), and 2-isopropoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazine (0.189 g, 0.72 mmol, CombiPhos Catalysis). The flask was sealed and evacuated under vacuum and backfilled with N2. DMF (2.7 mL) was added, and the reaction mixture was stirred at 80° C. for 18 h. The reaction was filtered through a 0.45 M filter and then diluted in water and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide tert-butyl (3R)-3-((6-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate (0.130 g, 0.21 mmol, 59% yield) as a light-yellow oil. MS (ESI, pos. ion) m/z: 616.2 (M+1).

Aufarbeitung

  1. customThe flask was sealed
  2. customevacuated under vacuum
  3. additionDMF (2.7 mL) was added
  4. filtrationThe reaction was filtered through a 0.45 M
  5. filtrationfilter
  6. additiondiluted in water
  7. extractionextracted with EtOAc (3×)
  8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was absorbed onto a plug of silica gel
  12. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  13. washeluting with a gradient of 0% to 50% EtOAc in hexane

Quellen und Nachweise

ORD-Eintrag
ord-20de5c8519204a21a47f85f901ae5343
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

Notizen zur Reaktion

Wird geladen…