Sodium hydride → HCID 72544463, compound

HRID 526687Notes

Reaction equation

HRID 526687 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH2:26][OH:27])[C:12]([CH3:25])=[N:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1.[H-].[Na+].C[O:31][C:32](=[O:45])[C:33]1[CH:38]=[CH:37][C:36]([NH:39][C:40](=[O:44])[CH:41](Br)[CH3:42])=[CH:35][CH:34]=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[C:9]1[CH:10]=[C:11]([CH2:26][O:27][CH:41]([CH3:42])[C:40]([NH:39][C:36]2[CH:37]=[CH:38][C:33]([C:32]([OH:45])=[O:31])=[CH:34][CH:35]=2)=[O:44])[C:12]([CH3:25])=[N:13][C:14]=1[C:15]1[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 89907741HCID 89907741, compoundHCID 899078694-(2-Bromo-propionylamino)-benzoic acid methyl ester

Product 1

HCID 72544463HCID 72544463, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 80 mg of [5-(2,4-Dichloro-phenyl)-2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-methanol in 2 ml of DMF were added 38 mg of sodium hydride (60% in mineral oil) at room temperature. After 15 min, 71 mg of tetrabutylammonium iodide and 83 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: 2 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-705bd51b1f9147aab34b1132d163f36f
Source dataset
uspto-grants-2016_05
Patent number
US09346757B2

Reaction notes

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