Phosphorus oxychloride → 5-(4-Bromo-2,6-difluorophenyl)-1,3,4-thiadiazol-2-amine
Reaktionsgleichung
[Br:1][C:2]1[CH:10]=[C:9]([F:11])[C:5]([C:6](O)=O)=[C:4]([F:12])[CH:3]=1.[NH:13]([C:15](=[S:17])[NH2:16])[NH2:14].O=P(Cl)(Cl)Cl>>[Br:1][C:2]1[CH:10]=[C:9]([F:11])[C:5]([C:6]2[S:17][C:15]([NH2:16])=[N:13][N:14]=2)=[C:4]([F:12])[CH:3]=1Komponenten
4
Reaktionsbedingungen
- Temperatur
- 78 °C
Versuchsvorschrift
A stirred mixture of 4-bromo-2,6-difluorobenzoic acid (5 g, 21.1 mmol) and hydrazinecarbothioamide (2.88 g, 31.6 mmol) was cooled under nitrogen in an ice bath. POCl3 (5.9 mL, 63.3 mmol) was added drop-wise and the reaction was stirred at ice bath temperature for 15 minutes then heated at 78° C. for 3 hours. The reaction mixture was cooled in an ice bath then quenched by addition of ice water (150 mL). The resulting solid was sonicated for 30 minutes to give a free stirring suspension which was left to slurry at room temperature for 72 hours. The solid was collected by vacuum filtration, rinsed with water, and re-suspended in saturated NaHCO3(aq) (150 mL). This suspension was stirred at room temperature for 18 hours then the solid was collected by vacuum filtration, rinsed with water, and dried in a vacuum oven for 24 hours to give the title compound (5.174 g, 84% yield) which was used in the next step without further purification. LC-MS: Rt 0.99 min; MS m/z 294.2 [M+2]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.68 (d, J=8.08 Hz, 2H), 7.57 (s, 2H).