Nicotinic Acid → 5-(Pyridin-3-yl)-1,3,4-thiadiazol-2-amine

Temperature

90 °C

5-pyridin-3-yl-[1,3,4]thiadiazol-2-ylamine was prepared as described by Turner et al. J. Med. Chem. 1988, 31, 898. Nicotinic acid (30 g, 0.24 mol) was added in portions to polyphosphoric acid (60 mL) under mechanical stirring. After stirring for 5 minutes, thiosemicarbazide (22.2 g, 0.24 mol) was added in portions. The reaction mixture was heated to 90° C. for 6 hours, cooled to room temperature over 14 hours, and re-heated to 40° C. to melt the solid yellow cake. Water was added (50 mL) dropwise via Pasteur pipette while stirring. The solution was cooled to 0° C., NH4OH (29% solution, approx 250 mL) was added dropwise over 2.5 hours to bring the pH to 14. The solids were collected by filtration, washed with water (150 mL) and dried in vacuo at 65° C. for 16 hours to afford the title compound as a beige-colored solid (21.7 g, 50%): mp 201-211° C.; IR (KBr thin film) 1508 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 8.95 (d, J=2.1 Hz, 1H), 8.62 (dd, J=4.5, 0.9 Hz, 1H), 8.14 (dt, J=8.4, 1.5 Hz, 1H), 7.51 (dd, J=8.1, 1.5 Hz, 1H); ESIMS m/z 179 ([M+H]+).

1. custom5-pyridin-3-yl-[1,3,4]thiadiazol-2-ylamine was prepared
2. temperaturecooled to room temperature over 14 hours
3. temperaturere-heated to 40° C.
4. stirringwhile stirring
5. temperatureThe solution was cooled to 0° C.
6. filtrationThe solids were collected by filtration
7. washwashed with water (150 mL)
8. customdried in vacuo at 65° C. for 16 hours

ORD record

ord-09bc6e39fc994b54a82d7f8dbaf41b1f

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604211B2