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

HRID 1404695Notes

Reaction equation

[C:1](O)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[NH2:10][NH:11][C:12]([NH2:14])=[S:13].[NH4+].[OH-]>O>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:1]2[S:13][C:12]([NH2:14])=[N:11][N:10]=2)[CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

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]+).

Workup

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

Sources & evidence

ORD record: ord-0980dd518cd44020897b23397a86abaf
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912338B2

Reaction notes

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