Acetic Acid → 2-Chloro-6-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-pyridine

HRID 241698Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:5]([NH:7][OH:8])=[NH:6].[C:13](O)(=O)[CH3:14]>CC(C)(C)C([O-])([O-])[O-]>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:6]=[C:13]([CH3:14])[O:8][N:7]=2)[CH:9]=[C:10]([CH3:12])[N:11]=1

Participants

Conditions

Temperature: 100 °C

Procedure

2-Chloro-N-hydroxy-6-methyl-isonicotinamidine (120 mg) was suspended in trimethylorthoacetate (3 ml) under inert atmosphere and acetic acid (0.3 ml) was added. The mixture was heated to 100° C. and stirred for 2 h. After cooling to room temperature the solvent was evaporated under reduced pressure and the residue partitioned between EtOAc and aqueous solution of NaHCO3. The organic layer was separated, washed with water and 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 10/0 to 9/1) affording the title compound (107 mg). HPLC (Rt)=3.17 min (method L).

Workup

additionwas added
temperatureAfter cooling to room temperature the solvent
customwas evaporated under reduced pressure
customthe residue partitioned between EtOAc and aqueous solution of NaHCO3
customThe organic layer was separated
washwashed with water and brine
customdried under Na2SO4
filtrationfiltered
customthe solvent was evaporated under reduced pressure
customThe crude was purified by flash column chromatography (10 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 10/0 to 9/1)

Sources & evidence

ORD record: ord-d7595250bda444e48bb2024365141c22
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653075B2

Reaction notes

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