Potassium Carbonate → HCID 69093144, compound

HRID 2174270Notes

Reaction equation

HRID 2174270 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, compound

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

Workup

  1. filtrationthe solids are filtered off through a cotton plug
  2. customThe solvent is removed in vacuo
  3. additionthe crude residue is diluted with water (e.g., about 50 mL)
  4. additiona mixture of dichloromethane and 2-propanol, e.g.
  5. additiona 5:1 mixture of dichloromethane and 2-propanol (e.g., about 50 mL)
  6. customThe layers are separated
  7. washthe organic layer is washed with water (e.g., about 50 mL)
  8. customdried
  9. custome.g., over sodium sulfate or magnesium sulfate, and the solvent is removed in vacuo
  10. additionTo the resulting crude 1-(2-fluorobenzyl)-N′-hydroxy-3-(pyridin-2-yl)-1H-1,2,4-triazole-5-carboximidamide is added trimethyl orthorfomate (e.g., about 4.5 mL, 41 mmol)
  11. temperatureThe solution is heated to about 100° C. for about 1.5 h
  12. customthe excess orthoformate is removed in vacuo
  13. customto give the crude product, I-34
  14. customPurification by silica gel chromatography (e.g., 20-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-4508a38e3ea5453cba9b1bce5e7d3d20
Source dataset
uspto-grants-2015_06
Patent number
US09061030B2

Reaction notes

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