2-cyano-N-(4-{[(3,4-dimethylisoxazol-5-yl)amino]sulfonyl}phenyl)acetamide synthesis

Yield:546090-57-7 82%

Reaction Conditions:

in 1,4-dioxane; for 6 h;Reflux;

Steps:

1 4.1.1. 2-Cyano-N-(4-{[(3,4-dimethylisoxazole-5-yl)amino]sulfonyl}phenyl)acetamide (3)

To a hot solution of sulfisoxazole 1 (5.34 g, 0.02 mol) in dioxan (60 mL) was added 1-cyanoacetyl-3,5-dimethylpyrazole 2 (3.26 g, 0.02 mol) and the reaction mixture was refluxed for 6 h. It was allowed to cool down to room temperature and the obtained solid was filtered off, washed with dioxan and recrystallized from ethanol/DMF to afford the target compound. Colorless crystals, yield (82%), mp 241-242 °C; IR (KBr) ν_max/cm^-1: 3263 (NH), 3183 (NH), 3073 (CH-Ar), 2964 (CH-sp³), 2261 (CN), 1699 (CO); ¹H NMR (500 MHz, DMSO-d₆): δ_ppm = 1.63 (s, 3H, CH₃), 2.09 (s, 3H, CH₃), 3.98 (s, 2H, CH₂), 7.72-7.77 (m, 4H, CH_Ar), 10.73 (s, 1H, NHSO₂), 10.97 (s, 1H, NHCO); ¹³C NMR (125 MHz, DMSO-d₆): δ_ppm = 5.8 (CH₃), 10.2 (CH₃), 27.0 (CH₂), 105.1 (CN), 115.5 (Phenyl-C₄), 119.0 (2C, Phenyl-C₂ and Phenyl-C₆), 128.0 (2C, Phenyl-C₃ and Phenyl-C₅), 134.3 (Phenyl-C₁), 142.5 (Isoxazole-C₄), 155.4 (Isoxazole-C₃), 161.3 (Isoxazole-C₅), 161.9 (CO); MS m/z (%): 335 ([M+H]⁺, 22.8), 334 (M⁺, 24.7), 223 (100), 175 (30.2), 159 (84.8), 111 (78.8), 96 (16.2), 83 (13.7), 68 (78.2); Anal. Calcd. for C₁₄H₁₄N₄O₄S (334.35): C, 50.29; H, 4.22; N, 16.76%, Found: C, 50.33; H, 4.17; N, 16.81%.

References:

Nasr, Tamer;Bondock, Samir;Eid, Sameh [European Journal of Medicinal Chemistry,2014,vol. 84,p. 491 - 504]