Cyclopropanecarboxylic acid → HCID 68378922, compound

Temperature

100 °C

An 8-mL vial was charged with cyclopropanecarboxylic acid (78.5 μL, 0.99 mmol) and DMF (1.0 mL). Carbonyldiimidazole (176 mg, 1.09 mmol) was added to the vial at room temperature. The clear reaction mixture was stirred for 2 h and then added to another 8-mL vial containing {1-[5-(N-hydroxycarbamimidoyl)-pyridin-2-yl]-cyclopropyl}-carbamic acid tert-butyl ester (430 mg, 1.47 mmol) in 1.0 mL of DMF. The resulting pale yellow reaction mixture was stirred at room temperature for 30 min and then heated at 100° C. for 16 h. The clear pale orange reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (2×20 mL). The organics were washed with of water (2×15 mL) and brine (15 mL), dried over Na2SO4, filtered, and concentrated to a crude oil. The crude oil was purified via normal phase flash chromatography on silica gel, eluting with 0-35% EtOAc/hexanes, to give {1-[5-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-pyridin-2-yl]-cyclopropyl}-carbamic acid tert-butyl ester (86 mg, 26%) as a white solid.

1. additionadded to another 8-mL
2. stirringThe resulting pale yellow reaction mixture was stirred at room temperature for 30 min
3. customThe clear pale orange reaction mixture was quenched with water (10 mL)
4. extractionextracted with ethyl acetate (2×20 mL)
5. washThe organics were washed with of water (2×15 mL) and brine (15 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated to a crude oil
9. customThe crude oil was purified via normal phase flash chromatography on silica gel
10. washeluting with 0-35% EtOAc/hexanes

ORD record

ord-e44b0a0267144f7ea346fde1514dbf27

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575360B2