Triethylamine → 3-(4-Fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid 3-trifluoromethyl-benzylamide

HRID 1423029Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1423029
Br[C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][CH:7]=1.CC[N:20]([CH2:23][CH3:24])[CH2:21]C.[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=C([CH:32]=[CH:33][CH:34]=1)CN.[C]=[O:38]>C1(C)C=CC=CC=1.[Cl-].[NH4+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=[C:24]([CH:32]=[CH:33][CH:34]=1)[CH2:23][NH:20][C:21]([C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][CH:7]=1)=[O:38]

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 759623-(Trifluoromethyl)benzylamineHCID 671955508-Bromo-3-(4-fluorophenyl)-imidazo[1,5-a]pyridineHCID 178418416HCID 178418416, Verbindung

Produkt 1

HCID 529356403-(4-Fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid 3-trifluoromethyl-benzylamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 1140TolueneLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of 8-bromo-3-(4-fluorophenyl)-imidazo[1,5-a]pyridine (0.100 g, 0.344 mmol), Et3N (95.0 μL, 0.683 mmol), 3-(trifluoromethyl)benzylamine (89.0 μL, 0.621 mmol), Pd[PhCN]2Cl2 (5.0 mg, 0.013 mmol), and dppf (21 mg, 0.038 mmol) in degassed toluene (10 mL) is placed in a pressure reactor. The stirred mixture is placed under 15 bars of carbon monoxide and warmed at 140° C. After 3 hours, the pressure reactor is cooled to room temperature, returned to atmospheric pressure and opened. The reaction mixture is diluted with saturated aqueous ammonium chloride (10 mL) and extracted with EtOAc (3×10 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (3×10 mL), brine (10 mL), dried over magnesium sulfate, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in dichloromethane. The resulting solid is triturated with ether-hexanes to afford the title compound.

Aufarbeitung

  1. customis placed in a pressure reactor
  2. temperaturethe pressure reactor is cooled to room temperature
  3. extractionextracted with EtOAc (3×10 mL)
  4. washThe combined organic layers are washed with saturated aqueous ammonium chloride (3×10 mL), brine (10 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with a gradient of 0-50% EtOAc in dichloromethane
  10. customThe resulting solid is triturated with ether-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-ed940bd698bc4d40be68049441a0a93b
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08927550B2

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