Triethylamine → 4-{5-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazol-3-yl}pyridine

To a solution of 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carbonyl chloride (Step 1, 65 mg, 0.26 mmol) in dichloromethane (4 mL) at 0° C. was added N′-hydroxypyridine-4-amidine (43 mg, 0.31 mmol) along with triethyl amine (0.073 mL). The mixture was stirred for 16 h at rt. The mixture was evaporated to dryness and DMF (3 mL) was added along with EDCl (75 mg, 0.392 mmol) and the mixture was stirred at 140° C. for 2 h. The reaction mixture was cooled and water (100 mL) and ethyl acetate (100 mL) was added. The layers were separated and the organic layer was washed with water (2×200 mL) and then dried with magnesium sulfate. The solvent was evaporated and the residue was purified with an ISCO CombiFlash Companion using gradient elution from 100% hexane to 40% ethyl acetate in hexane to afford the title compound as a white solid (65 mg, 75%): 1H NMR (300 MHz, CD2Cl2) 8.80 (d, 2H), 8.20 (d, 2H), 7.20 (d, 2H), 7.10 (d, 2H), 6.82 (s, 1H), 5.40 (s, 2H), 2.35 (m, 6H); ES-MS m/z 332.25 (MH)+, HPLC RT (Method B) 3.34 min.

1. customThe mixture was evaporated to dryness and DMF (3 mL)
2. stirringthe mixture was stirred at 140° C. for 2 h
3. temperatureThe reaction mixture was cooled
4. customThe layers were separated
5. washthe organic layer was washed with water (2×200 mL)
6. dry with materialdried with magnesium sulfate
7. customThe solvent was evaporated
8. customthe residue was purified with an ISCO CombiFlash Companion
9. washelution from 100% hexane to 40% ethyl acetate in hexane

ORD-Eintrag

ord-28b8dc49cbd7450dadc1e90fdada7fa8

Quelldatensatz

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08796253B2