(3-Amino-4-fluorophenoxy)acetic acid methyl ester → [2-Ethyl-8-fluoro-4-oxo-3-(4-pyrazol-1-ylbenzyl)-1,4-dihydroquinolin-5-yloxy]acetic acid methyl ester

HRID 1944274Notes

Reaction equation

HRID 1944274 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]([NH2:13])[CH:7]=1.C([O:17][C:18](=O)[CH:19]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH:35]=[CH:34][CH:33]=[N:32]2)=[CH:27][CH:26]=1)[C:20](=O)[CH2:21][CH3:22])C>O1CCOCC1.O>[CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:7]=1[C:18](=[O:17])[C:19]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]3[CH:35]=[CH:34][CH:33]=[N:32]3)=[CH:27][CH:26]=1)=[C:20]([CH2:21][CH3:22])[NH:13]2

Participants

5

Reactant 2

HCID 66717607(3-Amino-4-fluorophenoxy)acetic acid methyl esterHCID 674563603-Oxo-2-(4-pyrazol-1-ylbenzyl)pentanoic acid ethyl ester

Product 1

HCID 67457430[2-Ethyl-8-fluoro-4-oxo-3-(4-pyrazol-1-ylbenzyl)-1,4-dihydroquinolin-5-yloxy]acetic acid methyl esterYield 42.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of (3-amino-4-fluorophenoxy)acetic acid methyl ester (0.42 g) and 3-oxo-2-(4-pyrazol-1-ylbenzyl)pentanoic acid ethyl ester (0.63 g) in 1,4-dioxane (20 mL) was added to polyphosphoric acid (3 g) at 100° C., and the resulting mixture was stirred at 120° C. for 18 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The combined extracts were washed with water and saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate to afford title compound (0.39 g).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with water and saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue purified by column chromatography on silica gel
  7. washeluting with a mixture of cyclohexane and ethyl acetate

Sources & evidence

ORD record
ord-7a98662dabdb42859fbdac59c9b25ae3
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

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