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 869499Notes

Reaction equation

HRID 869499 reaction equation
[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

Participants

6

Reactant 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

Product 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-carboxamideYield 71%

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-afe9eba7c32b4879a391cb66e587362a
Source dataset
uspto-grants-2015_03
Patent number
US08969382B2

Reaction notes

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