Cesium carbonate → tert-butyl 4-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperazine-1-carboxylate

HRID 79410Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 79410
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][N:14]2[C:22]3[C:17](=[C:18]([NH:23][C:24]([C:26]4[N:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]5=[N:28][CH:27]=4)=[O:25])[CH:19]=[CH:20][CH:21]=3)[C:16]([CH2:35][CH3:36])=[N:15]2)[N:8]=1)(=O)=O.[N:39]1([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH2:35]([C:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][C:18]=2[NH:23][C:24]([C:26]2[N:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]3=[N:28][CH:27]=2)=[O:25])[N:14]([CH2:13][C:9]2[N:8]=[C:7]([N:42]3[CH2:41][CH2:40][N:39]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:44][CH2:43]3)[CH:12]=[CH:11][CH:10]=2)[N:15]=1)[CH3:36]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 866722116-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl trifluoromethanesulfonate

Produkt 1

HCID 67262131tert-butyl 4-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperazine-1-carboxylateAusbeute 37,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a reaction vial was added 6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl trifluoromethanesulfonate (30 mg, 0.0551 mmol; prepared according to Example 24, Step A), tert-butyl piperazine-1-carboxylate (20.5 mg, 0.110 mmol) and cesium carbonate (53.9 mg, 0.165 mmol). Toluene (2 mL) was added and argon was bubbled through the mixture for 10 minutes. To this solution was added rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.86 mg, 0.0110 mmol) and tris(dibenzylideneacetonyl)bis-palladium (5.05 mg; 0.00551 mmol). The reaction vial was sealed and the mixture was heated at 90° C. for 3 hours. The mixture was allowed to cool, filtered through Celite®, rinsing with toluene and concentrated under a stream of nitrogen. The material was purified using preparative thin layer chromatography on silica, eluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide solution to provide tert-butyl 4-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperazine-1-carboxylate (12 mg).

Aufarbeitung

  1. customargon was bubbled through the mixture for 10 minutes
  2. customThe reaction vial was sealed
  3. temperatureto cool
  4. filtrationfiltered through Celite®
  5. washrinsing with toluene
  6. concentrationconcentrated under a stream of nitrogen
  7. customThe material was purified
  8. washeluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide solution

Quellen und Nachweise

ORD-Eintrag
ord-ac71e2c60dd546d3920774e330cff0e7
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

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