Hydrazinecarboxaldehyde → 4-(4-Pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-phenol

To a solution of 4-Methoxy-N-pyridin-4-yl-benzamide (75 mg) in POCl3 (3 ml) was added PCl5 (68 mg) and the reaction mixture heated at reflux for 5 h. The reaction mixture was concentrated and dissolved in dimethyl formamide (2 ml) and Formic acid hydrazide (5 eq, 100 mg) was added and stirred for 2 h. The reaction mixture was concentrated and diluted with isopropanol (3 mL) and 0.25 ml of conc. HCl was added. The reaction mixture stirred for 18 h, quenched with 1 NaOH, extracted with dichloromethane, dried magenesium sulfate and concentrated. The crude product dissolved in methylene chloride (2 mL) and boron tribromide (0.63 mL 1.0M hexanes) was added at 0° C. The reaction mixture was warmed to ambient temperature and stirred for 18 h. The reaction mixture was quenched with 1 N NaOH and pH adjusted to 9, extracted with dichloromethane, dried magnesium sulfate, filtered and concentrated. Purification via Biotage MPLC chromatography eluting with 0-20% methanol/methylene chlroride provided the title compound (32 mg, 55%). MS: (M+H m/z=239.2).

1. temperaturethe reaction mixture heated
2. temperatureat reflux for 5 h
3. concentrationThe reaction mixture was concentrated
4. dissolutiondissolved in dimethyl formamide (2 ml)
5. concentrationThe reaction mixture was concentrated
6. additiondiluted with isopropanol (3 mL) and 0.25 ml of conc. HCl
7. additionwas added
8. stirringThe reaction mixture stirred for 18 h
9. customquenched with 1 NaOH
10. extractionextracted with dichloromethane
11. dry with materialdried magenesium sulfate
12. concentrationconcentrated
13. dissolutionThe crude product dissolved in methylene chloride (2 mL)
14. additionboron tribromide (0.63 mL 1.0M hexanes) was added at 0° C
15. stirringstirred for 18 h
16. customThe reaction mixture was quenched with 1 N NaOH
17. extractionextracted with dichloromethane, dried magnesium sulfate
18. filtrationfiltered
19. concentrationconcentrated
20. customPurification via Biotage MPLC chromatography
21. washeluting with 0-20% methanol/methylene chlroride

ORD record

ord-7099241919154d8197daed4588a5ac33

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07429665B2