Triphenylphosphine → 4-(3-Bromo-4-fluorophenyl)-3-{4-[(3-methoxypropyl)amino]-1,2,5-oxadiazol-3-yl}-1,2,4-oxadiazol-5(4H)-one

Temperature

0 °C

A solution of 3-methoxypropan-1-ol [Fluka product #38457] (3.1 mL, 32 mmol) and triphenylphosphine (8.4 g, 32 mmol) in tetrahydrofuran (93 mL) at 0° C. was treated with diisopropyl azodicarboxylate (6.7 mL, 34 mmol) dropwise. The reaction mixture was stirred at 0° C. for 15 min, treated with a solution of N-{4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}-2,2,2-trifluoroacetamide (10 g, 23 mmol) in tetrahydrofuran (47 mL), and stirred at 25° C. for 72 h. The reaction mixture was concentrated, diluted with ethyl acetate (200 mL), treated with trifluoroacetic acid (20 mL) and water (20 mL), and heated at 50° C. for 6 h. The reaction mixture was concentrated, rediluted with ethyl acetate (200 mL) and washed with water (3×80 mL), saturated sodium bicarbonate (2×80 mL) and brine (80 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to a crude residue. This material was purified on silica gel to give the desired product (6.4 g, 54%) as a white solid. LCMS for C14H14BrFN5O4 (M+H)+: m/z=414.0, 416.0.

1. stirringstirred at 25° C. for 72 h
2. concentrationThe reaction mixture was concentrated
3. additiondiluted with ethyl acetate (200 mL)
4. additiontreated with trifluoroacetic acid (20 mL) and water (20 mL)
5. temperatureheated at 50° C. for 6 h
6. concentrationThe reaction mixture was concentrated
7. additionrediluted with ethyl acetate (200 mL)
8. washwashed with water (3×80 mL), saturated sodium bicarbonate (2×80 mL) and brine (80 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated to a crude residue
12. customThis material was purified on silica gel

ORD record

ord-d424ea94f0254c7c83223bbfbd754a39

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088803B2