Réaction #1509581

Équation de réaction

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

Solvants

acetic acid

DMF

Conditions de réaction

Traitement

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

Mode opératoire

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)

Source