4-Toluenesulfonyl chloride → 2(2-Pyridyl)-5-ME-1,3,4-oxadiazole

HRID 1921354Notes

Reaction equation

HRID 1921354 reaction equation
[C:1]([NH:4][NH:5]C(=O)C1C=C(CC)C(OC)=NC=1C)(=[O:3])[CH3:2].S(Cl)([C:22]1[CH:28]=[CH:27][C:25](C)=[CH:24][CH:23]=1)(=O)=O.C([N:34]=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C>O1CCCC1>[CH3:2][C:1]1[O:3][C:22]([C:28]2[CH:27]=[CH:25][CH:24]=[CH:23][N:34]=2)=[N:5][N:4]=1

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 674924785-ethyl-6-methoxy-2-methyl-nicotinic acid N'-acetyl-hydrazide

Product 1

HCID 5950722(2-Pyridyl)-5-ME-1,3,4-oxadiazoleYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
145 °C

Procedure

Into each of two microwave vials is added 5-ethyl-6-methoxy-2-methyl-nicotinic acid N′-acetyl-hydrazide (100 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). Each 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 6.5 bar. LC/MS shows the reaction is complete. The product from both the vials are combined and evaporated, and the residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1). 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:ethyl acetate (3:1). Fractions containing the product are combined again and evaporated to give 3-ethyl-2-methoxy-6-methyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl-pyridine (95 mg, 73% yield, 2 steps). MS: m/e=234 (M+H); 1H NMR (CDCl3, δ, ppm): 7.86 (1H, s), 4.00 (3H, s), 2.79 (3H, s), 2.55-2.65 (5H, m), 1.21 (3H, t).

Workup

  1. customEach vial is flushed with nitrogen
  2. customsealed
  3. customevaporated
  4. customthe residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1)
  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:ethyl acetate (3:1)
  11. additionFractions containing the product
  12. customevaporated

Sources & evidence

ORD record
ord-2e767fd2d37b4fdc899a3cb791dc0afa
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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