Dimethylformamide → 5-Cyano-2-(3-methoxy-4-pyridin-2-ylphenyl)-1,3-benzoxazole

Temperature

120 °C

To 1 mL of degassed DMF was added 5-bromo-2-(3-methoxy-4-pyridin-2-ylphenyl)-1,3-benzoxazole (622 mg, 1.63 mmol), zinc cyanide (115 mg, 0.98 mmol), tris(dibenzylideneacetone)-dipalladium (0)-chloroform complex (30 mg, 0.029 mmol), and 1,1′-bisdiphenylphosphinoferrocene (41 mg, 0.073 mmol). The reaction mixture was degassed with argon for an additional 10 min and heated at 120° C. under an argon atmosphere for 20 h. The mixture was cooled to 80° C., 4 mL of a 4:1:4 saturated NH4Cl:NH4OH:H2O solution was added dropwise, and the mixture cooled to rt and stirred overnight. The mixture was cooled to −9° C. and filtered, the solid washed with 5 mL of a 4:1:5 sat. NH4Cl:NH4OH:H2O solution followed by 5 mL H2O, and dried under vacuum to a dark yellow solid. The crude solid was purified by column chromatography (20–80% EtOAc/hexanes) to give 5-cyano-2-(3-methoxy-4-pyridin-2-ylphenyl)-1,3-benzoxazole as a tan solid. 1H NMR (DMSO-d6, 300 MHz) δ 8.72 (d, 1H), 8.47 (d, 1H), 8.09–7.85 (m, 7H), 7.40 (ddd, 1H), 4.01 (s, 3H); MS (ESI) 328 (M+H)+.

1. customThe reaction mixture was degassed with argon for an additional 10 min
2. temperatureThe mixture was cooled to 80° C.
3. addition4 mL of a 4:1:4 saturated NH4Cl:NH4OH:H2O solution was added dropwise
4. temperaturethe mixture cooled to rt
5. temperatureThe mixture was cooled to −9° C.
6. filtrationfiltered
7. washthe solid washed with 5 mL of a 4:1:5 sat. NH4Cl
8. customdried under vacuum to a dark yellow solid
9. customThe crude solid was purified by column chromatography (20–80% EtOAc/hexanes)

ORD record

ord-dc5c21bbd0c14b558d315caa0f22ae81

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087601B2