Sodium hydride → HCID 72202295, compound

HRID 526715Notes

Reaction equation

HRID 526715 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)=[C:12]([CH3:24])[C:11]([CH2:25][OH:26])=[N:10]1.[H-].[Na+].C[O:30][C:31](=[O:44])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:43])[CH:40](Br)[CH3:41])=[CH:34][CH:33]=1>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:18][CH:19]=2)=[C:12]([CH3:24])[C:11]([CH2:25][O:26][CH:40]([CH3:41])[C:39]([NH:38][C:35]2[CH:36]=[CH:37][C:32]([C:31]([OH:44])=[O:30])=[CH:33][CH:34]=2)=[O:43])=[N:10]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 89907507[1-(2,4-Dichloro-phenyl)-4-methyl-5-(4-trifluoromethyl-phenyl)-1H-pyrazol-3-yl]-methanolHCID 899078694-(2-Bromo-propionylamino)-benzoic acid methyl ester

Product 1

HCID 72202295HCID 72202295, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 100 mg of [1-(2,4-Dichloro-phenyl)-4-methyl-5-(4-trifluoromethyl-phenyl)-1H-pyrazol-3-yl]-methanol in 3 ml of DMF were added 54 mg of sodium hydride (60% in mineral oil) at room temperature. After 15 min, 100 mg of tetrabutylammonium iodide and 117 mg of 4-(2-Bromo-propionylamino)-benzoic acid methyl ester were added and the reaction mixture was heated to 80° C. for 8 h. After cooling to room temperature and dilution with 1 M aqueous hydrochloric acid the reaction mixture was filtered through a chem Elut® cartridge by eluting with ethyl acetate. The solvents were removed under reduced pressure and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 24 mg.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationdilution with 1 M aqueous hydrochloric acid the reaction mixture was filtered through a chem Elut® cartridge
  3. washby eluting with ethyl acetate
  4. customThe solvents were removed under reduced pressure
  5. customthe residue was purified by preparative HPLC (
  6. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  7. additionThe fractions containing the product
  8. customwere evaporated
  9. customto yield a white solid

Sources & evidence

ORD record
ord-a025bae65e8e4d54b538f970ef8cc79e
Source dataset
uspto-grants-2016_05
Patent number
US09346762B2

Reaction notes

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