Reaction #1509581

Reaction equation

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

Solvents

acetic acid

DMF

Conditions

Workup

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

Procedure

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