Triethylamine → 2-(4-tert-Butylphenoxy)-N-(3,5-difluoro-4-[(methylsulfonyl)amino]benzyl}-acetamide

HRID 1350852Notes

Reaction equation

HRID 1350852 reaction equation
[C:1]([C:5]1[CH:15]=[CH:14][C:8]([O:9][CH2:10][C:11]([OH:13])=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:17][CH2:18][C:19]1[CH:24]=[C:23]([F:25])[C:22]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[C:21]([F:31])[CH:20]=1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.CN(C)C=O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([O:9][CH2:10][C:11]([NH:17][CH2:18][C:19]2[CH:20]=[C:21]([F:31])[C:22]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[C:23]([F:25])[CH:24]=2)=[O:13])=[CH:14][CH:15]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 157182-(4-Tert-butylphenoxy)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21097523N-[4-(aminomethyl)-2,6-difluorophenyl]methanesulfonamide hydrochloride

Product 1

HCID 210974672-(4-tert-Butylphenoxy)-N-(3,5-difluoro-4-[(methylsulfonyl)amino]benzyl}-acetamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To an N,N-dimethylformamide (DMF) (10 ml) solution of (4-tert-butylphenoxy)acetic acid (330 mg, 1.50 mmol) and N-[4-(aminomethyl)-2,6-difluorophenyl]methanesulfonamide hydrochloride (491 mg, 1.80 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDC) (431 mg, 2.25 mmol), 4-(dimethylamino)pyridine (DMAP) (55 mg, 0.45 mmol) and triethylamine (607 mg, 6.0 mmol) were added and the mixture was stirred for 15 hours at ambient temperature. The reaction mixture was then quenched with saturated aqueous solution of sodium bicarbonate and then crude products were extracted with methylene dichloride The organic layer was then washed with brine, dried over sodium sulfate. After filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give a residue, which was applied to an amino bound silica gel chromatography column and eluted with methylene dichloride/methanol=10/1 to furnish the title compound. Further, the title compound was recrystallized from ethyl acetate and hexane to furnish 199 mg (31% yield) of the title compound as a white solid.

Workup

  1. customThe reaction mixture was then quenched with saturated aqueous solution of sodium bicarbonate
  2. extractioncrude products were extracted with methylene dichloride The organic layer
  3. washwas then washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationAfter filtration
  6. customto separate solvent and sodium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customto give a residue, which
  9. washeluted with methylene dichloride/methanol=10/1

Sources & evidence

ORD record
ord-4d12b95ea30a463ab3ffaad42f703c60
Source dataset
uspto-grants-2007_05
Patent number
US07214824B2

Reaction notes

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