4-Toluenesulfonyl chloride → 3-Ethyl-2-methoxy-6-methyl-5-[1,3,4]oxadiazol-2-yl-pyridine

HRID 1921351Notes

Reaction equation

HRID 1921351 reaction equation
[CH:1]([NH:3][NH:4][C:5](=[O:17])[C:6]1[CH:11]=[C:10]([CH2:12][CH3:13])[C:9]([O:14][CH3:15])=[N:8][C:7]=1[CH3:16])=O.S(Cl)(C1C=CC(C)=CC=1)(=O)=O.C(N=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C>O1CCCC1>[CH2:12]([C:10]1[C:9]([O:14][CH3:15])=[N:8][C:7]([CH3:16])=[C:6]([C:5]2[O:17][CH:1]=[N:3][N:4]=2)[CH:11]=1)[CH3:13]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 674921155-ethyl-6-methoxy-2-methyl-nicotinic acid N'-formylhydrazide

Product 1

HCID 116371323-Ethyl-2-methoxy-6-methyl-5-[1,3,4]oxadiazol-2-yl-pyridineYield 8.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
145 °C

Procedure

Into a microwave vial is added 5-ethyl-6-methoxy-2-methyl-nicotinic acid N′-formylhydrazide (132 mg), tosyl chloride (64 mg, 0.336 mmol), and 2-t-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (2.2 mmol/g, 634 mg, 1.39 mmol) and anhydrous tetrahydrofuran (6 mL). The vial is flushed with nitrogen, sealed and heated in the CEM Discover microwave at 145° C. holding at that temperature for 3 min, with a maximum pressure of 6 bar. The reaction is evaporated and the residue is directly purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined and the solvent evaporated, and further purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined, evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (1:0 increasing to 99:1). Fractions containing the product are combined, evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (6:1). Fractions containing the product are combined and the solvent evaporated. The clean fraction containing the product is evaporated to give 3-ethyl-2-methoxy-6-methyl-5-[1,3,4]oxadiazol-2-yl-pyridine (10 mg, 8% yield). MS: m/e=220 (M+H); 1H NMR (CDCl3, δ, ppm): 8.45 (1H, d), 7.91 (1H, s), 4.01 (3H, s), 2.81 (3H, s), 2.61 (2H, q), 1.13 (3H, t).

Workup

  1. customThe vial is flushed with nitrogen
  2. customsealed
  3. customThe reaction is evaporated
  4. customthe residue is directly purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane
  5. additionFractions containing the product
  6. customthe solvent evaporated
  7. customfurther purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane
  8. additionFractions containing the product
  9. customevaporated
  10. customre-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (1:0 increasing to 99:1)
  11. additionFractions containing the product
  12. customevaporated
  13. customre-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (6:1)
  14. additionFractions containing the product
  15. customthe solvent evaporated
  16. additionThe clean fraction containing the product
  17. customis evaporated

Sources & evidence

ORD record
ord-0eed126facc940c580dd104c742f3a00
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

Loading…