Water → ethyl 5-[4-(2-isopropyloxy-3,5-dimethylpyridin-4-yl)-2-nitrophenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

HRID 1043953Notes

Reaction equation

HRID 1043953 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C@H:13]3[CH2:17][CH2:16][O:15][CH2:14]3)[N:11]=[CH:10][C:9]=2[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:4]([N+:23]([O-:25])=[O:24])[CH:3]=1.[N+](C1C=C(B2OC(C)(C)C(C)(C)O2)C=CC=1C1N([C@H]2CCOC2)N=CC=1C(OCC)=O)([O-])=O.I[C:60]1[C:65]([CH3:66])=[CH:64][N:63]=[C:62]([O:67][CH:68]([CH3:70])[CH3:69])[C:61]=1[CH3:71].O>CN(C=O)C>[CH:68]([O:67][C:62]1[C:61]([CH3:71])=[C:60]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[N:12]([C@H:13]4[CH2:17][CH2:16][O:15][CH2:14]4)[N:11]=[CH:10][C:9]=3[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:4]([N+:23]([O-:25])=[O:24])[CH:3]=2)[C:65]([CH3:66])=[CH:64][N:63]=1)([CH3:70])[CH3:69]

Participants

6

Reactant 4

HCID 962WaterHCID 866863514-Iodo-2-isopropyloxy-3,5-dimethylpyridineHCID 86686384Ethyl 5-(4-bromo-2-nitrophenyl)-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylateHCID 86686385Ethyl 5-[2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl][(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Product 1

HCID 86686383ethyl 5-[4-(2-isopropyloxy-3,5-dimethylpyridin-4-yl)-2-nitrophenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Ethyl 5-(4-bromo-2-nitrophenyl)-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate obtained in Preparation Example 7-(1) (200 mg) was converted to ethyl 5-[2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate by the same method as in Preparation Example 7-(2). A solution of 4-iodo-2-isopropyloxy-3,5-dimethylpyridine obtained in Preparation Example 47 (142 mg) in DMF (0.5 mL), and water (0.5 mL) were added to the reaction mixture, and the mixture was stirred at 110° C. for two hours. The reaction mixture was cooled to room temperature and then partitioned by adding ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 100%) to give the title compound (138.1 mg).

Workup

  1. additionwere added to the reaction mixture
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned
  4. additionby adding ethyl acetate and water
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 100%)

Sources & evidence

ORD record
ord-ced4c1933a0b48baac5ec6d9caa60eae
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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