Triethylamine → 6-Chloro-8-fluoro-2-oxo-4-phenyl-1,2-dihydro-quinoline-3-carbonitrile

HRID 1497230Notes

Reaction equation

HRID 1497230 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:13][C:14]1[C:19]([F:20])=[CH:18][C:17]([Cl:21])=[CH:16][C:15]=1[C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=O.C(N(CC)CC)C>ClCCl.CN(C=O)C.O.C1(C)C=CC=CC=1>[Cl:21][C:17]1[CH:16]=[C:15]2[C:14](=[C:19]([F:20])[CH:18]=1)[NH:13][C:4](=[O:6])[C:3]([C:1]#[N:2])=[C:22]2[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

9

Reactant 4

HCID 8471Triethylamine2×HCID 9740Cyanoacetic acidHCID 65578Oxalyl chlorideHCID 86683049(2-Amino-5-chloro-3-fluoro-phenyl)-phenyl-methanone

Product 1

HCID 866830506-Chloro-8-fluoro-2-oxo-4-phenyl-1,2-dihydro-quinoline-3-carbonitrileYield 33%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

2-Cyanoacetic acid (140 mg, 1.65 mmol) was co-evaporated with toluene two times and then suspended in dichloromethane (3 ml). One drop of DMF was added followed by dropwise addition of oxalyl chloride (304 mg, 206 μl, 2.4 mmol) at 0° C. The reaction mixture was stirred for 15 min at 0° C. and for another 2.5 h at room temperature. The solvent was then removed and the remaining residue was co-evaporated two times with dichloromethane. The residue was again dissolved in dichloromethane (3 ml) and a solution of (2-amino-5-chloro-3-fluoro-phenyl)-phenyl-methanone (374 mg, 1.5 mmol) and triethylamine (152 mg, 209 μl, 1.5 mmol) in dichloromethane (3 ml) was added dropwise at 0° C. The mixture was stirred at room temperature overnight. Then triethylamine (227 mg, 313 μl, 2.25 mmol) was added dropwise and the reaction mixture was stirred for 2 h before dichloromethane and water were added and the phases were separated. The aqueous layer was extracted with dichloromethane and the combined organic layers were washed with water and brine, dried with Na2SO4 and evaporated. The remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 80:20-45:55) to afford the title compound (146 mg, 33%) as white solid. MS (ESI): 299.3 (M+H)+.

Workup

  1. customThe solvent was then removed
  2. dissolutionThe residue was again dissolved in dichloromethane (3 ml)
  3. stirringThe mixture was stirred at room temperature overnight
  4. additionwere added
  5. customthe phases were separated
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. washthe combined organic layers were washed with water and brine
  8. dry with materialdried with Na2SO4
  9. customevaporated
  10. customThe remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 80:20-45:55)

Sources & evidence

ORD record
ord-abdce0bc79f947918c69332d246efcdb
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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