Pyridine → N-(6-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)pyridin-3-yl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide

HRID 1911874Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1911874
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[C:12]([F:15])([F:14])[F:13])[NH:5][CH:4]=[C:3]1[C:16]([OH:18])=O.[CH:19]12[N:25]([C:26]3[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([NH2:36])=[CH:28][CH:27]=3)[CH:22]([CH2:23][CH2:24]1)[CH2:21][CH2:20]2.N1C=CC=CC=1>CC1CCCO1.C(OCC)(=O)C>[CH:22]12[N:25]([C:26]3[N:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[C:29]([NH:36][C:16]([C:3]4[C:2](=[O:1])[C:11]5[C:6](=[CH:7][CH:8]=[CH:9][C:10]=5[C:12]([F:13])([F:14])[F:15])[NH:5][CH:4]=4)=[O:18])=[CH:28][CH:27]=3)[CH:19]([CH2:20][CH2:21]1)[CH2:24][CH2:23]2

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 156185574-Oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acidHCID 593162376-(7-Azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)pyridin-3-amine

Produkt 1

HCID 46195365N-(6-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)pyridin-3-yl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamideAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 73012-MethyltetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 4-oxo-5-(trifluoromethyl)-1H-quinoline-3-carboxylic acid (100 mg, 0.3889 mmol) and 6-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)pyridin-3-amine (110.1 mg, 0.4278 mmol) in 2-methyltetrahydrofuran (1.0 mL) was added propyl phosphonic acid cyclic anhydride (50% solution in ethyl acetate, 495.0 μL, 0.7778 mmol) and pyridine (61.52 mg, 62.90 μL, 0.7778 mmol). The reaction was capped and heated at 60° C. for 16 h. The reaction was cooled to room temperature, diluted with ethyl acetate (10 mL) and quenched with saturated Na2CO3 solution (6 mL). After stirring for 20 min the organic layer was separated, dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography (0-20% ethyl acetate in dichloromethane) provided N-(6-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)pyridin-3-yl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide (137 mg, 71% yield). LC/MS m/z 497.5 [M+H]+, retention time 1.92 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min).

Aufarbeitung

  1. customThe reaction was capped
  2. temperatureThe reaction was cooled to room temperature
  3. customquenched with saturated Na2CO3 solution (6 mL)
  4. customwas separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (0-20% ethyl acetate in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-2c00d51205b34cad93c9261a7e80f882
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08604203B2

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