Dimethylformamide → 2-(4-Tert-butylphenoxy)-n{3-fluoro-4-[(methylsulfonyl)amino]benzyl}acetamide

HRID 1350814Notes

Reaction equation

HRID 1350814 reaction equation
CN(C)C=O.[C:6]([C:10]1[CH:20]=[CH:19][C:13]([O:14][CH2:15][C:16]([OH:18])=O)=[CH:12][CH:11]=1)([CH3:9])([CH3:8])[CH3:7].Cl.[NH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[C:26]([F:35])[CH:25]=1.Cl.C(N=C=NCCCN(C)C)C>C(N(CC)CC)C>[C:6]([C:10]1[CH:11]=[CH:12][C:13]([O:14][CH2:15][C:16]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[C:26]([F:35])[CH:25]=2)=[O:18])=[CH:19][CH:20]=1)([CH3:7])([CH3:8])[CH3:9]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 157182-(4-Tert-butylphenoxy)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21097525N-[4-(aminomethyl)-2-fluorophenyl]methanesulfonamide hydrochloride

Product 1

HCID 210974712-(4-Tert-butylphenoxy)-n{3-fluoro-4-[(methylsulfonyl)amino]benzyl}acetamideYield 722.2%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a N,N-dimethylformamide (DMF) (10 ml) solution of (4-tert-butylphenoxy)acetic acid (50 mg, 0.2 mmol) and N-[4-(aminomethyl)-2-fluorophenyl]methanesulfonamide hydrochloride (40.4 mg, 0.2 mmol, J. Med. Chem. 2003, 46, 3116–3126), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDC) (112 mg, 0.6 mmol), 1-hydroxybenzotriazole(HOBt) monohydrate (catalytic amount 5 mg) and triethylamine (0.3 ml) were added and the mixture was stirred for 3 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 and 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 a silica gel chromatography column and eluted with methylene dichloride/methanol=9/1 to furnish 0.59 g (75% 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
  3. washThe organic layer was 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=9/1

Sources & evidence

ORD record
ord-81666781e49e4deba8987641460835a6
Source dataset
uspto-grants-2007_05
Patent number
US07214824B2

Reaction notes

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