Potassium Hydroxide → 6-(4-Bromo-3-fluorophenyl)-1,2,4-triazin-3-amine

Temperature

110 °C

A mixture of 1-(4-bromo-3-fluorophenyl)-2,2-diethoxyethanone (Step 4, 15.2 g, 50 mmol), aminoguanidine bicarbonate (10.2 g, 75 mmol) and potassium hydroxide (6.6 g, 100 mmol) in ethanol (200 mL) and water (4 mL) was refluxed overnight. The solvent was evaporated under reduced pressure and the residue was washed with acetonitrile and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (100 mL), washed with water, brine, and concentrated under reduced pressure. The residue was dissolved in ethanol (50 mL). To the solution was added 0.2N hydrochloric acid (50 mL). The resultant mixture was heated to 110° C. for 8 h, and cooled with an ice-water bath. The precipitate that formed was collected by filtration and washed with isopropanol to give the desired product. (5.5 g, 41%) LCMS: (M+H)=286.8/288.8. 1H-NMR (400 MHz, CDCl3): 8.60 (s, 1H), 7.79 (dd, J=8.6, 2.0 Hz, 1H), 7.68 (dd, J=8.3, 7.0 Hz, 1H), 7.61 (dd, J=8.3, 2.0 Hz, 1H), 5.43 (s, 2H).

1. temperaturewas refluxed overnight
2. customThe solvent was evaporated under reduced pressure
3. washthe residue was washed with acetonitrile
4. filtrationfiltered
5. concentrationThe filtrate was concentrated under reduced pressure
6. dissolutionThe residue was dissolved in dichloromethane (100 mL)
7. washwashed with water, brine
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in ethanol (50 mL)
10. additionTo the solution was added 0.2N hydrochloric acid (50 mL)
11. temperaturecooled with an ice-water bath
12. customThe precipitate that formed
13. filtrationwas collected by filtration
14. washwashed with isopropanol

ORD record

ord-5ba0a759f0e54e8d93f8fba91fdb20b3

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487096B2