Water → ethyl 1-(1,4-dioxepan-6-yl)-5-[4-(2-methoxy-3,5-dimethylpyridin-4-yl)-2-nitrophenyl]-1H-pyrazole-4-carboxylate

HRID 1043949Notes

Reaction equation

HRID 1043949 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]3[CH2:19][O:18][CH2:17][CH2:16][O:15][CH2:14]3)[N:11]=[CH:10][C:9]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:4]([N+:25]([O-:27])=[O:26])[CH:3]=1.[CH3:28][O:29][C:30]1[C:35]([CH3:36])=[C:34](B(O)O)[C:33]([CH3:40])=[CH:32][N:31]=1.C(OCC)(=O)C.O>O1CCOCC1>[O:18]1[CH2:19][CH:13]([N:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:34]4[C:33]([CH3:40])=[CH:32][N:31]=[C:30]([O:29][CH3:28])[C:35]=4[CH3:36])=[CH:3][C:4]=3[N+:25]([O-:27])=[O:26])=[C:9]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:10]=[N:11]2)[CH2:14][O:15][CH2:16][CH2:17]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 86686313ethyl 5-(4-bromo-2-nitrophenyl)-1-(1,4-dioxepan-6-yl)-1H-pyrazole-4-carboxylateHCID 86686333HCID 86686333, compound

Product 1

HCID 86686380ethyl 1-(1,4-dioxepan-6-yl)-5-[4-(2-methoxy-3,5-dimethylpyridin-4-yl)-2-nitrophenyl]-1H-pyrazole-4-carboxylateYield 155.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Water (0.2 mL), (2-methoxy-3,5-dimethylpyridin-4-yl)boronic acid (39.5 mg) obtained in Preparation Example 29, Pd(PPh3)4 (10.5 mg) and cesium carbonate (178 mg) were added to a solution of ethyl 5-(4-bromo-2-nitrophenyl)-1-(1,4-dioxepan-6-yl)-1H-pyrazole-4-carboxylate (80 mg) obtained in Preparation Example 9-(2) in 1,4-dioxane (1.3 mL), and the reaction mixture was stirred at 100° C. for 6.75 hours. (2-methoxy-3,5-dimethylpyridin-4-yl)boronic acid (15 mg) was added to the reaction mixture and the reaction mixture was stirred at 100° C. for 2.5 hours. After the reaction mixture was returned to mom temperature, ethyl acetate and water were added to the reaction mixture, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (silica gel, ethyl acetate/n-heptane, 20 to 33%) to give the title compound (64 mg).

Workup

  1. stirringthe reaction mixture was stirred at 100° C. for 2.5 hours
  2. additionwere added to the reaction mixture
  3. customthe organic layer was separated
  4. washThe resulting organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (silica gel, ethyl acetate/n-heptane, 20 to 33%)

Sources & evidence

ORD record
ord-49e66b04f40a4f76b0ff10c181aa7116
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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