Pyridine → 7-{[2-(4-Trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid ethyl ester

HRID 841780Notes

Reaction equation

HRID 841780 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=O)=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.[CH2:26]([O:28][C:29]([C:31]1[CH:32]=[N:33][C:34]2[C:39]([CH:40]=1)=[CH:38][CH:37]=[C:36]([NH2:41])[CH:35]=2)=[O:30])[CH3:27].N1C=CC=CC=1>ClCCl.CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl.CN(C)C=O>[CH2:26]([O:28][C:29]([C:31]1[CH:32]=[N:33][C:34]2[C:39]([CH:40]=1)=[CH:38][CH:37]=[C:36]([NH:41][C:11]([C:10]1[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:18])=[CH:8][CH:7]=3)=[N:17][CH:16]=[CH:15][CH:14]=1)=[O:13])[CH:35]=2)=[O:30])[CH3:27]

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 9877801Ethyl 7-aminoquinoline-3-carboxylateHCID 222627192-(4-Trifluoromethylphenyl)nicotinic acid

Product 1

HCID 698915467-{[2-(4-Trifluoromethyl-phenyl)-pyridine-3-carbonyl]-amino}-quinoline-3-carboxylic acid ethyl esterYield 122.5%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

2-(4-Trifluoromethyl-phenyl)-nicotinic acid (534 mg, 2.0 mmol) was suspended in 10 ml of dichloromethane, and oxalyl chloride (0.7 ml, 8.0 mmol) was added followed by a drop of dimethylformamide. After 2 h at room temperature, the volatiles were removed under vacuum, and to the residue was added 10 ml of chloroform, 7-amino-quinoline-3-carboxylic acid ethyl ester (216 mg, 1.0 mmol), pyridine (0.2 ml, 2.5 mmol) and 4-dimethylaminopyridine (12 mg, 0.1 mmol). After heating at reflux overnight, the reaction mixture was diluted with 50 ml of dichloromethane, washed with 35 ml of 2N NaOH, water, dried (magnesium sulfate) filtered, and concentrated under vacuum to afford 570 mg of a brown gum. This material was purified by silica gel chromatography eluting with 50 to 80% ethyl acetate in hexanes to provide 189 mg of the title compound as a light yellow solid.

Workup

  1. customthe volatiles were removed under vacuum
  2. temperatureAfter heating
  3. temperatureat reflux overnight
  4. washwashed with 35 ml of 2N NaOH, water
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-c291d90cfe094b79b0ae92800dd9c405
Source dataset
uspto-grants-2002_04
Patent number
US06369075B1

Reaction notes

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