Reaktion #1560477

Reaktionsgleichung

5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Intermediate D

5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

potassium carbonate

(2-chloro-4-(trifluoromethyl)phenyl)boronic acid

dioxane

→

5-(2-chloro-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Ausbeute 10.0%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was then cooled to room temperature
2. 2
   Sonstigethe organic layer was separated from the aqueous layer by pipet
3. 3
   workup.ADDITIONThe fractions containing product
4. 4
   workup.ADDITIONsaturated aq. NaHCO3 (15 mL) was added
5. 5
   WaschenThe aqueous layer was washed with ethyl acetate (1×100 mL)
6. 6
   TrocknenThe combined organic layers were dried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated under a vacuum

Vorschrift

A pressure vessel was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate D) (110 mg, 0.211 mmol), potassium carbonate (146 mg, 1.057 mmol), (2-chloro-4-(trifluoromethyl)phenyl)boronic acid (56.9 mg, 0.254 mmol), tetrakis(triphenylphosphine)palladium(0) (24.42 mg, 0.021 mmol), dioxane (1409 μl) and water (705 μl). The reaction was heated in a microwave at 100° C. for 30 min. The mixture was then cooled to room temperature and the organic layer was separated from the aqueous layer by pipet. The resulting organic layer was then injected as is onto a reverse phase HPLC (Column: Gemini 150×30 mm, 5 μm, Phenomenex, Torrance, Calif., Flow rate: 40 mL/min, Mobile phase: 0.1% TFA in ACN and water). The fractions containing product were combined and saturated aq. NaHCO3 (15 mL) was added. The aqueous layer was washed with ethyl acetate (1×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under a vacuum to provide 5-(2-chloro-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (10 mg, 0.021 mmol) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.22 (d, J=8.90 Hz, 1H) 7.36 (dd, J=7.09, 1.03 Hz, 1H) 7.43-7.58 (m, 4H) 7.65 (d, J=7.92 Hz, 1H) 7.85 (s, 1H) 7.99-8.09 (m, 2H) 8.31 (d, J=1.76 Hz, 1H); m/z (ESI) 470 (M+H)+.

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