Phosphorus oxychloride → 5-(4-Bromo-2,6-difluorophenyl)-1,3,4-thiadiazol-2-amine

Temperature

78 °C

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).

1. temperaturewas cooled under nitrogen in an ice bath
2. temperatureThe reaction mixture was cooled in an ice bath
3. customthen quenched by addition of ice water (150 mL)
4. customThe resulting solid was sonicated for 30 minutes
5. customto give a free stirring suspension which
6. waitwas left
7. waitto slurry at room temperature for 72 hours
8. filtrationThe solid was collected by vacuum filtration
9. washrinsed with water
10. stirringThis suspension was stirred at room temperature for 18 hours
11. filtrationthe solid was collected by vacuum filtration
12. washrinsed with water
13. customdried in a vacuum oven for 24 hours

ORD record

ord-1e5f9a2e2f1148888669b25ea74fa741

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040712B2