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

Temperature

0 °C

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. 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 either taken up with toluene (6 mL/mmol of carboxylic acid derivative) and pyridine (2 mL/mmol of carboxylic acid derivative) or with ACN (8.5 mL/mmol of carboxylic acid derivative). The resulting mixture was heated at a temperature between 80° C. to reflux for a period of 12 to 72 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 evaporated under reduced pressure. Purification by flash chromatography or precipitation gave the expected oxadiazole derivative.

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 a temperature between 80° C.
7. temperatureto reflux for a period of 12 to 72 hours
8. additionThe reaction mixture was diluted with an adequate solvent, such as Et2O, MTBE or EtOAc
9. washwashed with water and brine
10. extractionThe aqueous layers were extracted once
11. dry with materialdried (MgSO4 or Na2SO4)
12. customthe solvents were evaporated under reduced pressure
13. customPurification
14. customby flash chromatography or precipitation

ORD record

ord-cc9c9ef9743745c0a013695f53e882b8

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815919B2