N-(3-methoxyphenyl)pivalamide → N-(2-{[5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridin-2-yl]-hydroxy-methyl}-3-methoxy-phenyl)-2,2-dimethyl-propionamide

HRID 419133Notes

Reaction equation

HRID 419133 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[CH:7][CH:8]=1.[Li]CCCC.[Mg+2].[Br-].[Br-].CCOCC.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([S:36]([NH:39][C:40]2[C:41]([CH:47]=[O:48])=[N:42][CH:43]=[C:44]([Cl:46])[CH:45]=2)(=[O:38])=[O:37])=[CH:32][C:31]=1[C:49]([F:52])([F:51])[F:50]>C1COCC1>[Cl:46][C:44]1[CH:45]=[C:40]([NH:39][S:36]([C:33]2[CH:34]=[CH:35][C:30]([Cl:29])=[C:31]([C:49]([F:50])([F:52])[F:51])[CH:32]=2)(=[O:37])=[O:38])[C:41]([CH:47]([OH:48])[C:4]2[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=2[NH:9][C:10](=[O:15])[C:11]([CH3:12])([CH3:14])[CH3:13])=[N:42][CH:43]=1

Participants

6

Reactant 4

HCID 546358N-(3-methoxyphenyl)pivalamideHCID 9903262Magnesium bromide diethyl etherateHCID 579424914-chloro-N-(5-chloro-2-formyl-pyridin-3-yi)-3-trifluoromethyl-benzenesulfonamideHCID 178418339Butyllithium

Product 1

HCID 57942304N-(2-{[5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridin-2-yl]-hydroxy-methyl}-3-methoxy-phenyl)-2,2-dimethyl-propionamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of N-(3-methoxy-phenyl)-2,2-dimethyl-propionamide (1.11 g, 4.8 mmol) in anhydrous THF at 0° C. was added a solution of n-BuLi (3.65 mL, 9.1 mmol) in hexanes. After 45 minutes, anhydrous MgBr2-Et2O (1.23 g, 4.8 mmol) was added in one portion and stirring was continued at the same temperature for 1 h. The mixture was then cooled to −78° C. and solid 4-chloro-N-(5-chloro-2-formyl-pyridin-3-yl)-3-trifluoromethyl-benzenesulfonamide (300 mg, 0.75 mmol) was added in one portion and slowly warmed to room temperature over 4 h. The mixture was then quenched with saturated aqueous NH4Cl (10 mL), and extracted with EtOAc (3×75 mL). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using ethyl acetate-hexane to provide N-(2-{[5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridin-2-yl]-hydroxy-methyl}-3-methoxy-phenyl)-2,2-dimethyl-propionamide: MS m/z 606.0 (M+H)+.

Workup

  1. waitwas continued at the same temperature for 1 h
  2. temperatureslowly warmed to room temperature over 4 h
  3. customThe mixture was then quenched with saturated aqueous NH4Cl (10 mL)
  4. extractionextracted with EtOAc (3×75 mL)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-8346c049ab6a40d989e0b627de78de2d
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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