2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-4-phenyl-1,3-oxazole

A solution of 2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-4-phenyl-4,5-dihydro-1,3-oxazole (Example 69, 100 mg, 0.3 mmol) in dioxane (10 mL) was treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (137 mg, 0.6 mmol), and the resultant mixture was heated at reflux for 16 h. After being cooled to rt, the mixture was diluted with water (10 mL), extracted with ethyl acetate (1×25 mL), washed with NaOH (0.5 N aq., 1×25 mL) and brine (1×25 mL), dried (Na2SO4), filtered, and concentrated to dryness. The crude material was purified by HPLC eluting with a gradient from 20% to 80% acetonitrile in water containing 0.1% TFA. The combined fractions were then diluted with ethyl acetate and washed with NaHCO3 (sat. aq., 1×25 mL) dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a white solid (15 mg, 15%): 1H NMR (300 MHz, CD3OD) δ 8.19 (s, 1H), 7.73 (d, 2H), 7.29-7.35 (m, 2H), 7.21-7.25 (m, 1H), 7.04 (d, 2H), 6.95 (d, 2H), 6.62 (s, 1H), 5.28 (s, 2H), 2.20 (s, 3H), 2.18 (s, 3H); ES-MS m/z 330.12, HPLC RT (Method B) 3.89 min.

1. temperatureat reflux for 16 h
2. extractionextracted with ethyl acetate (1×25 mL)
3. washwashed with NaOH (0.5 N aq., 1×25 mL) and brine (1×25 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated to dryness
7. customThe crude material was purified by HPLC
8. washeluting with a gradient from 20% to 80% acetonitrile in water containing 0.1% TFA
9. additionThe combined fractions were then diluted with ethyl acetate
10. washwashed with NaHCO3 (sat. aq., 1×25 mL)
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated under reduced pressure

ORD record

ord-fc35e2b6f1fa4ef3abec3dfe614bc522

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796253B2