Picolinic acid → 3,5-Bis(2-pyridyl)-1,2,4-oxadiazole

HRID 1908853Notes

Reaction equation

HRID 1908853 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.O[NH:53][C:54]([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][N:57]=1)=[NH:55]>CN(C=O)C.O1CCOCC1>[N:57]1[CH:58]=[CH:59][CH:60]=[CH:61][C:56]=1[C:54]1[N:55]=[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[O:9][N:53]=1

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 178513306HCID 178513306, compound

Product 1

HCID 143584633,5-Bis(2-pyridyl)-1,2,4-oxadiazoleYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the appropriate pyridine carboxylic acid (1 eq.) and DIPEA (3 eq.) in DMF is added PyBOP (1.05 eq.) at 0° C. The mixture is stirred for 15 min at 0° C. The appropriate N-hydroxy pyridine-carboxamidine (1.05 eq.) is added and stirring is continued for 1 to 8 h at 0° C. to rt. The reaction is monitored by LC-MS. Upon complete conversion, the reaction is quenched with water and sat. aq. NaHCO3-solution. The mixture is extracted with diethyl ether, EA or DCM. The org. extracts are dried over MgSO4, filtered and evaporated to give the crude hydroxyamidine ester. This material is dissolved in dioxane and the resulting solution is stirred at 70-90° C. for 4 to 24 h. The solvent is removed in vacuo and the crude product is purified by either CC on silica gel, chromatography on prep. TLC plates or by HPLC to give the desired 3,5-dipyridyl-[1,2,4]oxadiazol in 30-80% yield.

Workup

  1. stirringstirring
  2. waitis continued for 1 to 8 h at 0° C. to rt
  3. customUpon complete conversion, the reaction is quenched with water and sat. aq. NaHCO3-solution
  4. extractionThe mixture is extracted with diethyl ether, EA or DCM
  5. dry with materialextracts are dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude hydroxyamidine ester
  9. stirringthe resulting solution is stirred at 70-90° C. for 4 to 24 h
  10. customThe solvent is removed in vacuo
  11. customthe crude product is purified by either CC on silica gel, chromatography on prep

Sources & evidence

ORD record
ord-a7d49379482b4d1f8e4260a8b43b0296
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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