Phosgene → HCID 57502368, compound

A suspension of 1-phenyl-3-pyridin-2-yl-thiourea (1.0 g, 4.4 mmol) and dimethyl sulfate (0.45 mL, 4.8 mmol) in acetonitrile (6 mL) was heated at reflux for 4 hours. The mixture was cooled to room temperature and the volatiles were evaporated. 1b) To the residue was added hydroxylamine hydrochloride (0.67 g, 9.6 mmol), N,N-diisopropylethylamine (3.3 mL, 19 mmol) and dichloromethane (8 mL). The mixture was stirred at room temperature for 18 hours. Water (10 mL) was added. A nitrogen sparge tube connected to a bleach scrubber was fitted to the reaction flask. The mixture was sparged with nitrogen. The resulting oily liquid was partitioned between ethyl acetate (100 mL) and water. The organic layer was washed with water (3×20 mL), dried over magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. 1c) To the residue in acetonitrile (10 mL) at −5° C. was added potassium carbonate (1.5 g, 11 mmol) followed by dropwise addition of 20% phosgene in toluene (1:4, phosgene:toluene, 2.6 mL, 4.9 mmol). The mixture was stirred for 1 hour at −5° C. then warmed to room temperature. Additional 20% phosgene in toluene (1.0 mL) and potassium carbonate (1.0 g) was added to the mixture and stirred for 48 hours. The volatiles were evaporated and the residue was partitioned between ethyl acetate (100 mL) and water. The organic layer was washed with water (3×20 mL), dried over magnesium sulfate and filtered. The solvent was evaporated under reduced pressure and the product was purified via flash chromatography utilizing an ISCO automated purification apparatus (silica gel column, elution gradient of 5%→100% ethyl acetate in heptane). Phenyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl-amine was isolated as a yellow solid (0.17 g, 18%). MP=180-184° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.46-8.42 (m, 1H), 7.63-7.59 (m, 2H), 7.51-7.41 (m, 2H), 7.38-7.33 (m, 2H), 7.31 (br s, 1H), 7.02-6.97 (m, 1H), 6.90-6.85 (m, 1H). MS=211 (MH)+.

1. temperaturewas heated
2. temperatureat reflux for 4 hours
3. customthe volatiles were evaporated
4. customA nitrogen sparge tube
5. customwas fitted to the reaction flask
6. customThe mixture was sparged with nitrogen
7. customThe resulting oily liquid was partitioned between ethyl acetate (100 mL) and water
8. washThe organic layer was washed with water (3×20 mL)
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. customThe solvent was evaporated under reduced pressure
12. stirringThe mixture was stirred for 1 hour at −5° C.
13. temperaturethen warmed to room temperature
14. stirringstirred for 48 hours
15. customThe volatiles were evaporated
16. customthe residue was partitioned between ethyl acetate (100 mL) and water
17. washThe organic layer was washed with water (3×20 mL)
18. dry with materialdried over magnesium sulfate
19. filtrationfiltered
20. customThe solvent was evaporated under reduced pressure
21. customthe product was purified via flash chromatography
22. custompurification apparatus (silica gel column, elution gradient of 5%→100% ethyl acetate in heptane)

ORD record

ord-2d3fa1654e1447d09847badd7d2d2e1e

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501936B2