Reacción #1509581

Ecuación de reacción

hydrazine acetate

2-Chloro-6-methyl-isonicotinamide

N,N-dimethylformamide dimethyl acetal

→

2-Chloro-6-methyl-4-(1H-[1,2,4]triazol-3-yl)-pyridine

Disolventes

acetic acid

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was cooled to room temperature
2. 2
   TemperaturaThe mixture was heated to 90° C.
3. 3
   workup.STIRRINGstirred for 1 h
4. 4
   OtroThe solvent was removed under reduced pressure
5. 5
   Otrothe residue partitioned between saturated aqueous solution of NaHCO3 and EtOAc
6. 6
   OtroThe organic phase was separated
7. 7
   Lavadowashed with brine
8. 8
   Otrodried under Na2SO4
9. 9
   Filtraciónfiltered
10. 10
    Otrothe solvent was evaporated under reduced pressure
11. 11
    OtroThe crude was purified by flash column chromatography (10 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 1/1 to 3/7)

Procedimiento

2-Chloro-6-methyl-isonicotinamide (1.23 g) and N,N-dimethylformamide dimethyl acetal (1.05 ml) were dissolved in dry DMF (4 ml) under inert atmosphere and the resulting solution was heated to 90° C. and stirred for 1 h. The reaction mixture was cooled to room temperature and a solution of hydrazine acetate (3.32 g) in acetic acid (8 ml) was dropwise added. The mixture was heated to 90° C. and stirred for 1 h. The solvent was removed under reduced pressure and the residue partitioned between saturated aqueous solution of NaHCO3 and EtOAc. The organic phase was separated, washed with brine, dried under Na2SO4, filtered and the solvent was evaporated under reduced pressure. The crude was purified by flash column chromatography (10 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 1/1 to 3/7) affording 2-Chloro-6-methyl-4-(1H-[1,2,4]triazol-3-yl)-pyridine (0.92 g). GC (Rt)=13.21 min (method=3A)

Fuente