Ethyl bromoacetate → 2-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)acetic acid

Temperature

0 °C

To a solution of 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (203 mg, 0.535 mmol) in DMF (5 mL), NaH (43 mg, 1.07 mmol, 60% in mineral oil) is added at 0° C. The mixture is stirred at 0° C. and ethyl bromoacetate (98 mg, 0.588 mmol) is added. Stirring is continued at 0° C. for 30 min, then at rt for 72 h. The reaction is quenched by adding water (2 mL) and the mixture is concentrated. The residue is dissolved in THF (10 mL), methanol (10 mL) and 2 N aq. LiOH (10 mL). The mixture is stirred at 60° C. for 2 h before it is cooled to rt, acidified by adding 2 N aq. HCl and extracted three times with EA (3×20 mL). The combined org. extracts are concentrated and the crude product is purified by prep. HPLC to give the title compound (146 mg) as a white solid; LC-MS: tR=1.14 min, [M+H]+=438.07; 1H NMR (CDCl3): δ 7.90 (s, 1H), 7.88 (s, 1H), 7.79 (s br, 1H), 7.50 (s, 1H), 7.29 (s, 1H), 4.57 (s, 2H), 4.01 (s, 3H), 3.20-3.29 (m, 1H), 2.79 (q, J=7.5 Hz, 2H), 2.42 (s, 3H), 2.04-2.16 (m, 2H), 1.82-1.95 (m, 4H), 1.68-1.80 (m, 2H), 1.34 (t, J=7.5 Hz, 3H).

1. stirringStirring
2. waitat rt for 72 h
3. customThe reaction is quenched
4. additionby adding water (2 mL)
5. concentrationthe mixture is concentrated
6. dissolutionThe residue is dissolved in THF (10 mL)
7. stirringThe mixture is stirred at 60° C. for 2 h before it
8. temperatureis cooled to rt
9. additionby adding 2 N aq. HCl
10. extractionextracted three times with EA (3×20 mL)
11. concentrationextracts are concentrated
12. customthe crude product is purified by prep

ORD record

ord-c3a70b2ea917497ab9998fa5c46d0c07

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133179B2