Reaktion #434522

Reaktionsgleichung

hydrochloric acid

4-Acetyl-N-(5-methylisoxazole-3-yl)benzenesulfonamide

4-methoxy-2-(2-morpholin-4-ylethoxy)-5-thien-2-ylbenzaldehyde

lithium methoxide

→

title compound

Ausbeute 88.0%

4-{3E-[4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thien-2-ylphenyl]acryloyl}-N-(5-methyl-isoxazol-3-yl)benzenesulfonamide hydrochloride

Ausbeute 88.0%

Lösungsmittel

dimethylformamide methanol

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Extraktionextracted with ethyl acetate:tetrahydrofuran (1:1, 3×20 mL)
3. 3
   SonstigeThe combined organic extracts were evaporated to dryness
4. 4
   Temperaturwarmed to 60° C.
5. 5
   Sonstigeto obtain complete
6. 6
   workup.DISSOLUTIONdissolution
7. 7
   Temperaturto cool to room temperature
8. 8
   SonstigeThe resulting precipitate was collected
9. 9
   Filtrationon filter paper
10. 10
    Sonstigedried in vacuo

Vorschrift

4-Acetyl-N-(5-methylisoxazole-3-yl)benzenesulfonamide (Ex-1B, 0.30 g, 0.86 mmol) and 4-methoxy-2-(2-morpholin-4-ylethoxy)-5-thien-2-ylbenzaldehyde (Ex-14A, 0.24 g, 0.86 mmol) were dissolved in a dimethylformamide-methanol solution (6.0 mL, 7:3). After complete dissolution, lithium methoxide (0.13 g, 3.4 mmol) was added and the resulting orange slurry was stirred in the dark at room temperature for 1 h. Upon completion, as determined by HPLC, the mixture was diluted with water (8.0 mL), acidified with a 1 N hydrochloric acid solution, and extracted with ethyl acetate:tetrahydrofuran (1:1, 3×20 mL). The combined organic extracts were evaporated to dryness. The crude oil was taken up in ethanol (10 mL) and warmed to 60° C. to obtain complete dissolution and allowed to cool to room temperature. The resulting precipitate was collected on filter paper and dried in vacuo to yield 0.46 g (88%) of the title compound as a pale orange solid, mp>260° C. 1H-NMR (300 MHz, DMSO-d6) 8.34 (d, 2H, J=9.0 Hz), 8.32 (s, 1H), 8.12 (d, 1H, J=15.9 Hz), 8.03 (d, 2H, J=9.0 Hz), 7.93 (d, 1H, J=15.9 Hz), 7.69 (d, 1H, J=3.3 Hz), 7.56 (d, 1H, J=5.4 Hz), 7.15 (dd, 1H, J=5.4, 3.3 Hz), 6.92 (s, 1H), 6.18 (s, 1H), 4.65 (brs, 2H), 4.03 (s, 3H), 3.97 (brs, 4H), 3.69 (brs, 2H), 3.50–3.23 (brs, 4H), 2.31 (s, 3H). Anal. Calcd. for C30H32ClN3O7S2.H2O: C, 54.25; H, 5.16; N, 6.33; S, 9.66; Found: C, 54.10; H, 4.91; N, 6.39; S, 9.68. HRMS (ESI) Calcd. for C30H32ClN3O7S2: 610.1681 (—HCl) (M+H)+. Found: 610.1673.

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