Water → HCID 178461232, Verbindung

HRID 81268Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 81268
Cl[C:2]1[C:7]2[N:8]([CH2:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]3)[C:9]([N:11]3[CH2:16][CH2:15][O:14][C@@H:13]4[CH2:17][CH2:18][CH2:19][C@@H:12]34)=[N:10][C:6]=2[CH:5]=[C:4]([Cl:28])[N:3]=1.[Cl:29][C:30]1[CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[C:33]([F:36])=[N:34][CH:35]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CCOC(C)=O>[Cl:28][C:4]1[N:3]=[C:2]([C:32]2[C:33]([F:36])=[N:34][CH:35]=[C:30]([Cl:29])[CH:31]=2)[C:7]2[N:8]([CH2:20][C@H:21]3[CH2:22][CH2:23][C@H:24]([CH3:27])[CH2:25][CH2:26]3)[C:9]([N:11]3[CH2:16][CH2:15][O:14][C@@H:13]4[CH2:17][CH2:18][CH2:19][C@@H:12]34)=[N:10][C:6]=2[CH:5]=1

Komponenten

6

Edukt 4

HCID 962Water2×HCID 10796Cesium carbonateHCID 533983785-Chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 178461234HCID 178461234, Verbindung

Produkt 1

HCID 178461232HCID 178461232, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

4,6-dichloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (racemic, 422 mg, 1 mmol), 5-chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (340 mg, 2 mmol) and Cs2CO3 (980 mg, 3 mmol) were added to degassed dioxane:water (10 mL: 2 mL), followed by the addition of [1,1′-bis(di-tert-butylphosphino)ferrocene]PdCl2 (130 mg, 0.2 mmol). The reaction was heated at 90° C. for 24 hours. Water and EtOAc were added. The aqueous layer was extracted with EtOAc several times. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified on a silica gel column (0 to 60% EtOAc/hexanes) to afford 6-chloro-4-(5-chloro-2-fluoropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (racemic). MS ES calc'd. for C26H30Cl2FN5O [M+H]+ 518. found 518.

Aufarbeitung

  1. customto degassed dioxane
  2. extractionThe aqueous layer was extracted with EtOAc several times
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a silica gel column (0 to 60% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c789d65199174fb0920133c415d19328
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846657B2

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