Dimethylformamide → 3,4-dicyclopropyl-5-(4-pentylbicyclo[2.2.2]oct-1-yl)-4H-1,2,4-triazole

Temperature

130 °C

To a solution of N-cyclopropylcyclopropanecarboxamide (2-A) (26 mg, 0.210 mmol) in 0.50 ml toluene was added methyl triflate (1.45 mg, 1 eq) and the reaction was heated at 100° C. for 5-7 min until all of the amide went into solution. To this crude solution was added 0.740 mL of a 0.3 M solution of 4-pentylbicyclo[2.2.2]octane-1-carbohydrazide in DMF (1.1 eq, crude, prepared as described in Step A of Example 1) followed by triethylamine (0.059 mL, 2 eq) and the mixture was heated at 130° C. for 4 h. After this time the solvent was removed under reduced pressure, and the residue was chromatographed on C-18 reverse phase (gradient 90% water to 100% acetonitrile, 0.1% TPA). The fractions containing the compound were determined by LCMS, added to 200 mL of methylene chloride, and extracted with saturated aqueous sodium bicarbonate. The organic layer was dried over magnesium sulfate and evaporated under diminished. The residue was lyophilized from benzene to afford 3,4-dicyclopropyl-5-(4-pentylbicyclo[2.2.2]oct-1-yl)-4H-1,2,4-triazole (2-B); MS (ESI+)=328.3 (M+1).

1. customAfter this time the solvent was removed under reduced pressure
2. customthe residue was chromatographed on C-18 reverse phase (gradient 90% water to 100% acetonitrile, 0.1% TPA)
3. additionThe fractions containing the compound
4. additionadded to 200 mL of methylene chloride
5. extractionextracted with saturated aqueous sodium bicarbonate
6. dry with materialThe organic layer was dried over magnesium sulfate
7. customevaporated

ORD record

ord-ccf9927c7ff24b85a97bb67107f64af1

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026264B2