Sodium Carbonate → tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

HRID 1529350Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529350
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[F:18])[CH:9]=2)[N:4]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([N:39]3[CH2:44][CH2:43][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:41][CH2:40]3)[CH:36]=[N:37][CH:38]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:3]=[C:2]2[C:33]1[CH:34]=[C:35]([N:39]2[CH2:40][CH2:41][CH:42]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[CH2:43][CH2:44]2)[CH:36]=[N:37][CH:38]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 679597623-bromo-5-(2,6-difluoro-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazoleHCID 67959870Tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate

Produkt 1

HCID 67960050tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamateAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178478230HCID 178478230, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

A mixture of 3-bromo-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (90 mg, 0.229 mmol), tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate (115 mg, 0.286 mmol), Na2CO3, 2.0 M (0.229 mL, 0.458 mmol) and dichloro 1,1′-bis(diphenylphosphino) ferrocene palladium (II) (18.69 mg, 0.023 mmol, Strem) in dioxane (3 mL) was capped, degassed and backfilled with argon. The reaction was heated to 135° C. in a microwave for 45 min. The reaction mixture was diluted with EtOAc (50 mL) and washed with brine (50 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluent: 0-3% MeOH/DCM), affording tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (120 mg, 89%). MS (ESI, pos. ion) m/z: 590.3 (M+1).

Aufarbeitung

  1. customwas capped
  2. customdegassed
  3. additionThe reaction mixture was diluted with EtOAc (50 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel chromatography (eluent: 0-3% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-206cca678a2d45ff80490bbf37155eee
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

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