Methanesulfonamide → 4-(4-Chlorophenoxy)-2-fluoro-5-(2-methoxypyridin-3-yl)-N-(methylsulfonyl)benzamide

HRID 1620315Notes

Reaction equation

HRID 1620315 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[C:15]([C:16]3[C:17]([O:22][CH3:23])=[N:18][CH:19]=[CH:20][CH:21]=3)=[CH:14][C:10]([C:11](O)=[O:12])=[C:9]([F:24])[CH:8]=2)=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:60][S:61]([NH2:64])(=[O:63])=[O:62]>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[C:15]([C:16]3[C:17]([O:22][CH3:23])=[N:18][CH:19]=[CH:20][CH:21]=3)=[CH:14][C:10]([C:11]([NH:64][S:61]([CH3:60])(=[O:63])=[O:62])=[O:12])=[C:9]([F:24])[CH:8]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666667494-(4-Chlorophenoxy)-2-fluoro-5-(2-methoxypyridin-3-yl)benzoic acid

Product 1

HCID 666677684-(4-Chlorophenoxy)-2-fluoro-5-(2-methoxypyridin-3-yl)-N-(methylsulfonyl)benzamideYield 117.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(4-chlorophenoxy)-2-fluoro-5-(2-methoxypyridin-3-yl)benzoic acid (Preparation 30, 236 mg, 0.63 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (462 mg, 1.21 mmol), N,N-diisopropylethylamine (838 μL, 4.81 mmol) in dichloromethane (40 mL) and dimethylformamide (5.4 mL) which had been stirred at room temperature for 10 minutes was added methyl sulfonamide (151 mg, 1.59 mmol). The reaction was heated at 45° C. for 18 hours under a nitrogen atmosphere. The mixture was cooled to room temperature and concentrated in vacuo to afford a brown residue. The brown residue was partitioned between aqueous hydrochloric acid (0.5 M, 40 mL) and dichloromethane (100 mL). The organic extract was washed with aqueous hydrochloric acid (0.5 M, 2×40 mL), dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown oil (335 mg). The product was purified by flash column chromatography eluting with dichloromethane/methanol (100% to 97%) to afford a yellow gum (91.0 mg). A portion of this material (50 mg) was purified by A-HPLC to afford the title compound as an off-white solid (35.8 mg, 13%):

Workup

  1. temperatureThe reaction was heated at 45° C. for 18 hours under a nitrogen atmosphere
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customto afford a brown residue
  5. customThe brown residue was partitioned between aqueous hydrochloric acid (0.5 M, 40 mL) and dichloromethane (100 mL)
  6. extractionThe organic extract
  7. washwas washed with aqueous hydrochloric acid (0.5 M, 2×40 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1ba974613af243a88632fc30d07fad14
Source dataset
uspto-grants-2014_07
Patent number
US08772343B2

Reaction notes

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