Cesium carbonate → 3-[(E)-2-(4-Fluorophenyl)-vinyl]-4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-1H-indazole-1,5-dicarboxylic Acid 1-tert-butyl Ester 5-ethyl Ester

HRID 34048Notes

Reaction equation

HRID 34048 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:31])=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[N:10]=[C:9]2/[CH:22]=[CH:23]/[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)=[O:5])[CH3:2].Br[CH2:33][CH2:34][O:35][CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][O:37]1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:31][CH2:33][CH2:34][O:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][O:37]2)=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[N:10]=[C:9]2/[CH:22]=[CH:23]/[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 10796Cesium carbonate2×HCID 25517Ammonium ChlorideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyran3×HCID 1359878973-[(E)-2-(4-Fluorophenyl)-vinyl]-4-hydroxy-1H-indazole-1,5-dicarboxylic Acid 1-tert-butyl ester 5-ethyl Ester

Product 1

HCID 597971113-[(E)-2-(4-Fluorophenyl)-vinyl]-4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-1H-indazole-1,5-dicarboxylic Acid 1-tert-butyl Ester 5-ethyl EsterYield 56.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 200 mg of 3-[(E)-2-(4-fluorophenyl)-vinyl]-4-hydroxy-1H-indazole-1,5-dicarboxylic acid 1-tert-butyl ester 5-ethyl ester in 13 mL of N,N-dimethylformamide were added 196.5 mg of 2-(2-bromoethoxy)-tetrahydropyran and 306.3 mg of cesium carbonate, stirred for 1 hour and 30 minutes at room temperature, stirred at 50° C. for 17 hours, added with 196.5 mg of 2-(2-bromoethoxy)-tetrahydropyran and 306.3 mg of cesium carbonate, stirred for 3 hours at room temperature and for 2 hours at 50° C., added with 554 mg of 2-(2-bromoethoxy)-tetrahydropyran, and further stirred at 50° C. for 4 hours. Then, the reaction solution was added saturated aqueous ammonium chloride, extracted twice with ethyl acetate, and the resultant organic layer was washed once with saturated brine and dried over magnesium sulfate. The solvent was evaporated, and the crude product was purified and separated by silica gel column chromatography, to afford 147 mg of the title compound as a colorless oil.

Workup

  1. stirringstirred at 50° C. for 17 hours
  2. stirringstirred for 3 hours at room temperature and for 2 hours at 50° C.
  3. stirringfurther stirred at 50° C. for 4 hours
  4. extractionextracted twice with ethyl acetate
  5. washthe resultant organic layer was washed once with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was evaporated
  8. customthe crude product was purified
  9. customseparated by silica gel column chromatography

Sources & evidence

ORD record
ord-ec0353e48ca847c1983b4272642af2e5
Source dataset
uspto-grants-2008_09
Patent number
US07429609B2

Reaction notes

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