Pyridine → {3-[4-(4-Cyclopropylpyrazol-1-yl)benzyl]-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy}acetic acid methyl ester

HRID 1944339Notes

Reaction equation

HRID 1944339 reaction equation
[F:1][CH:2]([F:33])[O:3][C:4]1[C:13]2[C:8](=[C:9]([F:20])[CH:10]=[CH:11][C:12]=2[O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[N:7]=[C:6]([CH2:21][CH3:22])[C:5]=1[CH2:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.[CH:34]1([C:37]2[CH:38]=[N:39][NH:40][CH:41]=2)[CH2:36][CH2:35]1.N1C=CC=CC=1>O>[CH3:19][O:18][C:16](=[O:17])[CH2:15][O:14][C:12]1[CH:11]=[CH:10][C:9]([F:20])=[C:8]2[C:13]=1[C:4]([O:3][CH:2]([F:33])[F:1])=[C:5]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([N:39]3[CH:38]=[C:37]([CH:34]4[CH2:36][CH2:35]4)[CH:41]=[N:40]3)=[CH:26][CH:25]=1)[C:6]([CH2:21][CH3:22])=[N:7]2

Participants

5

Reactant 3

HCID 1049PyridineHCID 131639734-Cyclopropyl-1H-pyrazoleHCID 67458287(4-{[4-Difluoromethoxy-2-ethyl-8-fluoro-5-(2-methoxy-2-oxoethoxy) quinolin-3-yl]methyl}phenyl)boronic acid

Product 1

HCID 67458601{3-[4-(4-Cyclopropylpyrazol-1-yl)benzyl]-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy}acetic acid methyl esterYield 79.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of (4-{[4-difluoromethoxy-2-ethyl-8-fluoro-5-(2-methoxy-2-oxoethoxy) quinolin-3-yl]methyl}phenyl)boronic acid (0.1 g), 4-cyclopropyl-1H-pyrazole (0.047 g), cuprous acetate (0.078 g) and pyridine (3 mL) was heated at 40° C. for 24 hours. The mixture was cooled to room temperature, diluted with water (10 mL) and extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1:0 to 7:3 by volume) gave title compound as pale green oil (0.09 g).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by column chromatography on silica gel
  7. washeluting with a mixture of cyclohexane and ethyl acetate (1:0 to 7:3 by volume)

Sources & evidence

ORD record
ord-21ae246daebd4e6c908ece53fdbbdf7c
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

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