Yield:-

Reaction Conditions:

in ethanol; for 3 h;Reflux;

Steps:

14 4.8.11 2-(3,5-dimethyl-4H-1,2,4-triazol-4-yl)benzoic acid (8)

Anhydride 28²¹ (1.0 g, 6.21 mmol, 1.1 equiv.) and acetylhydrazide (418 mg, 5.64 mmol, 1.0 equiv.) were refluxed in EtOH (56 mL, 0.1 M) for 3 h.²² The reaction was cooled down to r.t. and then dry loaded on celite. The crude was purified using C18 functionlized silica gel using a gradient from 5:95 MeCN: H₂O to 1:1 MeCN:H₂O. The fractions containing the desired product were lyophilized. Yield: 27%, white solid. ¹H NMR (500 MHz, DMSO-d₆) δ 13.38 (s, 1H), 8.05 (dd, J = 7.8, 1.6 Hz, 1H), 7.78 (dt, J = 7.7, 1.7 Hz, 1H), 7.68 (dt, J = 7.6, 1.3 Hz, 1H), 7.49 (dd, J = 7.8, 1.3 Hz, 1H), 2.01 (s, 6H). ¹³C NMR (126 MHz, DMSO-d₆) δ 165.8, 150.5, 133.6, 133.0, 131.5, 130.3, 129.6, 129.6, 10.6. HRMS (DART) m/z: [M+H]⁺ calcd for C₁₁H₁₂N₃O₂ 218.0930, found 218.0930.

References:

Mader;Mendoza-Sanchez, Rodrigo;Iqbal, Aman;Dong, Aiping;Dobrovetsky;Corless, Victoria B.;Liew, Sean K.;Houliston, Scott R.;De Freitas, Renato Ferreira;Smil;Sena, Carlo C. Dela;Kennedy, Steven;Diaz, Diego B.;Wu, Hong;Dombrovski, Ludmila;Allali-Hassani, Abdellah;Min, Jinrong;Schapira, Matthieu;Vedadi, Masoud;Brown, Peter J.;Santhakumar, Vijayaratnam;Yudin, Andrei K.;Arrowsmith, Cheryl H. [Bioorganic and Medicinal Chemistry,2019,vol. 27,# 17,p. 3866 - 3878]