Methanesulfonamide → 3-chloro-4-(4-chloro-3-(trifluoromethyl)phenoxy)-2-fluoro-N-(methylsulfonyl)benzamide

HRID 2359271Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2359271
[Cl:1][C:2]1[C:3]([F:23])=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=1)[C:5](O)=[O:6].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:55][S:56]([NH2:59])(=[O:58])=[O:57]>ClCCl>[Cl:1][C:2]1[C:3]([F:23])=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=1)[C:5]([NH:59][S:56]([CH3:55])(=[O:58])=[O:57])=[O:6]

Komponenten

7

Edukt 5

HCID 72879MethanesulfonamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 580463433-Chloro-4-(4-chloro-3-(trifluoromethyl)phenoxy)-2-fluorobenzoic acid

Produkt 1

HCID 565927153-chloro-4-(4-chloro-3-(trifluoromethyl)phenoxy)-2-fluoro-N-(methylsulfonyl)benzamideAusbeute 82,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

3-chloro-4-(4-chloro-3-(trifluoromethyl)phenoxy)-2-fluorobenzoic acid (Preparation 153, 0.133 g, 0.360 mmol) was slurried in dichloromethane (0.6 mL). N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (100 mg, 0.54 mmol), 1-hydroxybenzotriazole (49 mg, 0.36 mmol) and N,N-diisopropylethylamine (75 μL, 0.43 mmol) were added to the slurry. The reaction mixture was stirred 20 minutes then methanesulfonamide (100 mg, 1.1 mmol) was added and the stirring continued for 18 hours at ambient temperature. The solvent was removed in vacuo to leave a residue. The residue was purified by semi-preparative reverse phase HPLC (Phenomenex 100×21.2 mm 10 micron C18 column. 20 mL/minutes. Gradient 85% A to 100% B over 25 minutes. Solvent A: 7800 water/200 acetonitrile/8 trifluoroacetic acid. Solvent B: 7200 acetonitrile/800 water/8 trifluoroacetic acid, 254 nM UV detection) to afford the title compound as a white solid (132 mg).

Aufarbeitung

  1. waitthe stirring continued for 18 hours at ambient temperature
  2. customThe solvent was removed in vacuo
  3. customto leave a residue
  4. customThe residue was purified by semi-preparative reverse phase HPLC (Phenomenex 100×21.2 mm 10 micron C18 column. 20 mL/minutes. Gradient 85% A to 100% B over 25 minutes. Solvent A: 7800 water/200 acetonitrile/8 trifluoroacetic acid. Solvent B: 7200 acetonitrile/800 water/8 trifluoroacetic acid, 254 nM UV detection)

Quellen und Nachweise

ORD-Eintrag
ord-3e012675ba9e4eaeb58811a6eef6e494
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08685977B2

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