Sodium Hydroxide → HCID 58367173, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of 3-cyano-4-fluorobenzoic acid (37.3 g, 225 mmol) and thiosemicarbazide (22.6 g, 248 mmol) was added POCl3 (148 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h and then heated to 85° C. for 6 h. The resulting yellow solution was cooled to room temperature and concentrated to 50% volume. The residue was cooled to 0° C. and water was added (300 mL) drop wise. (Caution: exothermic and violent reaction with gas evolution). The mixture was heated to 90° C. for 1 h then cooled to room temperature. EA was added EA (300 mL) and the reaction mixture stirred for 10 min and before filtration. The collected solid was dispersed into water (270 mL), cooled to 0° C., and neutralized with 50% NaOH aqueous solution to pH8. The resulting solid was filtered, washed thoroughly with water, and dried under high vacuum to afford 26 g (52%) of 5-(5-amino-1,3,4-thiadiazol-2-yl)-2-fluorobenzonitrile TDZ INT-1 as pale yellow solid which was used in next experiment without purification. LCMS-ESI (m/z) calculated for C9H5FN4S: 220.0; found 221.1 [M+H]+, tR=2.44 min. 1H NMR (400 MHz, DMSO) δ 8.29 (dd, J=6.1, 2.3 Hz, 1H), 8.19 (ddd, J=8.9, 5.2, 2.4 Hz, 1H), 7.64 (t, J=9.0 Hz, 1H), 7.58 (s, 2H). 13C NMR (101 MHz, DMSO) δ 169.82, 164.25, 161.68, 133.68, 131.65, 128.96, 117.96, 113.77, 101.59.

Provenance & Evidence