Diisopropylethylamine → 3-(3-Amino-1,2,4-oxadiazol-5-yl)-1-azabicyclo(2.2.1)heptane

HRID 572535

Reaction equation

HRID 572535 reaction equation
[CH3:1][CH2:2][N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])C.CN([C:13]([O:17][N:18]1N=NC2C=CC=[N:24][C:19]1=2)=[N+:14](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOCC.CC(OC)(C)C.CCOC(C)=O>[CH2:9]1[CH:6]2[CH:1]([C:13]3[O:17][N:18]=[C:19]([NH2:24])[N:14]=3)[CH2:2][N:3]([CH2:4]2)[CH2:7]1

Participants

7

Reactant 2

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 1639383-(3-Amino-1,2,4-oxadiazol-5-yl)-1-azabicyclo(2.2.1)heptane

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

DIEA (2.0 to 2.2 eq) and HATU (1.0 to 1.1 eq) were added into a solution of the carboxylic acid derivative (1 eq) in anhydrous DMF (4 mL/mmol of carboxylic acid derivative) cooled at 0° C. The resulting mixture was stirred at 0° C. for a period of 5 to 30 minutes. Then the amidoxime derivative (1.0 to 1.2 eq) was added neat or as a DMF solution (2 mL/mmol of amidoxime derivative). The resulting mixture was stirred at 0° C. or RT for a period of 30 minutes to 18 hours. The reaction mixture was diluted with an adequate solvent, such as Et2O, MTBE or EtOAc, and then washed with water and brine. The aqueous layers were extracted once. The organic layers were combined, dried (MgSO4 or Na2SO4) and the solvents were removed under reduced pressure. The residue was taken up with ACN (8.5 mL/mmol of carboxylic acid derivative). The resulting mixture was heated at 150° C. for 30 min under MW irradiation. The reaction mixture was diluted with an adequate solvent, such as Et2O, MTBE or EtOAc, and then washed with water and brine. The aqueous layers were extracted once. The organic layers were combined, dried (MgSO4 or Na2SO4) and the solvents were evaporated under reduced pressure. Purification by flash chromatography or precipitation gave the expected oxadiazole derivative.

Workup

  1. stirringThe resulting mixture was stirred at 0° C. or RT for a period of 30 minutes to 18 hours
  2. washwashed with water and brine
  3. extractionThe aqueous layers were extracted once
  4. dry with materialdried (MgSO4 or Na2SO4)
  5. customthe solvents were removed under reduced pressure
  6. temperatureThe resulting mixture was heated at 150° C. for 30 min under MW irradiation
  7. additionThe reaction mixture was diluted with an adequate solvent, such as Et2O, MTBE or EtOAc
  8. washwashed with water and brine
  9. extractionThe aqueous layers were extracted once
  10. dry with materialdried (MgSO4 or Na2SO4)
  11. customthe solvents were evaporated under reduced pressure
  12. customPurification
  13. customby flash chromatography or precipitation

Sources & evidence

ORD record
ord-3f3ff1cd86914be3acf10723ca14c5f0
Source dataset
uspto-grants-2015_05
Patent number
US09029405B2

Linked notes

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