Phosphorus oxychloride → 5-(2-Chloro-4-iodophenyl)-1,3,4-thiadiazol-2-amine

Temperature

78 °C

A stirred mixture of 2-chloro-4-iodobenzoic acid (2 g, 7.08 mmol) and hydrazinecarbothioamide (0.968 g, 10.62 mmol) was cooled under nitrogen in an ice bath. POCl3 (1.98 mL, 21.24 mmol) was added drop-wise and the reaction mixture was heated at 78° C. for 3 hours. The reaction mixture was cooled in an ice bath before quenching by addition of ice water (50 mL). The resulting solid/cake was sonicated for 1 hour to give a free stirring suspension. This material was left to slurry at room temperature for ˜18 hours then filtered under vacuum and rinsed with water to afford the crude product as a pale yellow/orange solid. The solid was re-suspended in saturated NaHCO3(aq) (50 mL), slurried at room temperature for 2 hours, then collected by vacuum filtration to afford the title compound as a pale yellow solid (2.05 g, 86% yield). LC-MS: Rt 1.20 min; MS m/z 337.8 [M]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.01 (d, J=1.52 Hz, 1H), 7.76-7.82 (m, 2H), 7.50 (s, 2H).

1. temperaturewas cooled under nitrogen in an ice bath
2. temperatureThe reaction mixture was cooled in an ice bath
3. custombefore quenching by addition of ice water (50 mL)
4. customThe resulting solid/cake was sonicated for 1 hour
5. customto give a free stirring suspension
6. waitThis material was left
7. filtrationthen filtered under vacuum
8. washrinsed with water
9. customto afford the crude product as a pale yellow/orange solid
10. waitslurried at room temperature for 2 hours
11. filtrationcollected by vacuum filtration

ORD record

ord-ccf6a7103c384e219caad740d0c705d0

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040712B2