1,2-Dichloroethane → HCID 59598405, compound

HRID 2359705Notes

Reaction equation

HRID 2359705 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:15]([OH:17])=O)[C:5](=[O:14])[N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:7]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[O:30][CH3:31])[N:26]=[CH:25][CH:24]=[C:23]2[O:32][C:33]1[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][C:34]=1[F:40].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:15]([NH:39][C:36]2[CH:37]=[CH:38][C:33]([O:32][C:23]3[C:22]4[C:27](=[CH:28][C:29]([O:30][CH3:31])=[C:20]([O:19][CH3:18])[CH:21]=4)[N:26]=[CH:25][CH:24]=3)=[C:34]([F:40])[CH:35]=2)=[O:17])[C:5](=[O:14])[N:6]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:7]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamineHCID 13157209HCID 13157209, compound

Product 1

HCID 59598405HCID 59598405, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Bromo-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid (0.458 g, 1.6 mmol), 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorobenzenamine (0.49 g, 1.6 mmol), EDC (0.45 g, 2.3 mmol), and HOAt (0.21 g, 1.6 mmol) were added to a reaction flask then suspended in N,N-dimethylformamide (7.0 mL). N,N-diisopropylethylamine (0.95 ml, 5.5 mmol) was added to the reaction mixture and stirring was continued at room temperature overnight. The reaction mixture was diluted with ethyl acetate and water and then extracted with ethyl acetate. A precipitate formed between the layers. The aqueous layer was filtered and the precipitate collected. The filtered aqueous layer was extracted with ethyl acetate (1×). The combined ethyl acetate layers were washed with brine and then dried over sodium sulfate. The precipitate was dissolved in dichloromethane and also dried over sodium sulfate. All of the organic layers were combined and concentrated under vacuum. The remaining residue was purified by silica gel chromatography (1% methanol/dichloromethane to 2% methanol/dichloromethane) to give 5-bromo-N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide as a yellow solid (0.846 g, 1.4 mmol, 92% yield). MS (ESI pos. ion) m/z: 590 (MH+). Calc'd exact mass for C29H21BrFN3O5: 589.

Workup

  1. extractionextracted with ethyl acetate
  2. customA precipitate formed between the layers
  3. filtrationThe aqueous layer was filtered
  4. customthe precipitate collected
  5. extractionThe filtered aqueous layer was extracted with ethyl acetate (1×)
  6. washThe combined ethyl acetate layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. dissolutionThe precipitate was dissolved in dichloromethane
  9. dry with materialalso dried over sodium sulfate
  10. concentrationconcentrated under vacuum
  11. customThe remaining residue was purified by silica gel chromatography (1% methanol/dichloromethane to 2% methanol/dichloromethane)

Sources & evidence

ORD record
ord-27caa59d431349358fd82ce8d555ee93
Source dataset
uspto-grants-2014_04
Patent number
US08685983B2

Reaction notes

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