Potassium Carbonate → HCID 69093144, compound

HRID 2174280Notes

Reaction equation

HRID 2174280 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]([C:10]#[N:11])=[N:8][C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:6]1.[C:22](=[O:25])([O-])[O-].[K+].[K+].Cl.[NH2:29]O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(OCC)(=O)C>[F:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]([C:10]2[N:29]=[CH:22][O:25][N:11]=2)=[N:8][C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:6]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 69093841HCID 69093841, compound

Product 1

HCID 69093144HCID 69093144, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-(2-fluorobenzyl)-3-(pyridin-2-yl)-1H-1,2,4-triazole-5-carbonitrile (I-33, 100 mg, 0.358 mmol) and potassium carbonate (198 mg, 1.43 mmol) in methanol (3.6 mL) was added hydroxylamine hydrochloride (75 mg, 1.1 mmol). The solution was heated at 70° C. for 1.25 h, at which point the solution was diluted with ethyl acetate (20 mL) and the solids were filtered off through a cotton plug. The solvent was removed in vacuo and the crude residue was diluted with water (50 mL) and a 5:1 mixture of dichloromethane and 2-propanol (50 mL). The layers were separated and the organic layer was washed with water (50 mL), dried over magnesium sulfate, and the solvent was removed in vacuo. To the resulting crude 1-(2-fluorobenzyl)-N′-hydroxy-3-(pyridin-2-yl)-1H-1,2,4-triazole-5-carboximidamide was added trimethyl orthorfomate (4.5 mL, 41 mmol) and a catalytic amount of p-toluensulfonic acid monohydrate (3.4 mg, 0.018 mmol). The solution was heated at 100° C. for 1.5 h, and the excess orthoformate was removed in vacuo to give the crude product as a dull yellow solid. Purification by silica gel chromatography (20-80% ethyl acetate in hexanes) gave 3-(1-(2-fluorobenzyl)-3-(pyridin-2-yl)-1H-1,2,4-triazol-5-yl)-1,2,4-oxadiazole, I-34 (52 mg, 0.16 mmol, 46% yield over 2 steps) as a white solid.

Workup

  1. filtrationthe solids were filtered off through a cotton plug
  2. customThe solvent was removed in vacuo
  3. additionthe crude residue was diluted with water (50 mL)
  4. additiona 5:1 mixture of dichloromethane and 2-propanol (50 mL)
  5. customThe layers were separated
  6. washthe organic layer was washed with water (50 mL)
  7. dry with materialdried over magnesium sulfate
  8. customthe solvent was removed in vacuo
  9. additionTo the resulting crude 1-(2-fluorobenzyl)-N′-hydroxy-3-(pyridin-2-yl)-1H-1,2,4-triazole-5-carboximidamide was added trimethyl orthorfomate (4.5 mL, 41 mmol)
  10. temperatureThe solution was heated at 100° C. for 1.5 h
  11. customthe excess orthoformate was removed in vacuo
  12. customto give the crude product as a dull yellow solid
  13. customPurification by silica gel chromatography (20-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-367f023daffb490ab8f10b00ae9c8368
Source dataset
uspto-grants-2015_06
Patent number
US09061030B2

Reaction notes

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