1,2-Dimethoxyethane → D-159687

Participants

Reaction Conditions

Reaction Steps

To a 20 mL vial equipped with a magnetic stir bar and a screw cap was added [4-(3-bromo-4-methoxy-benzyl)-phenyl]-urea (I-44) synthesized above compound (250 mg, 0.746 mmol), dimethoxyethane (5 mL), ethanol (1 mL) and water (1 mL). To this mixture were added 3-chlorophenylboronic acid (140 mg, 0.895 mmol), potassium phosphate (316 mg, 1.49 mmol) and tetrakis(triphenylphosphine) palladium (30 mg, 0.0254 mmol). The stirring reaction mixture was degassed by bubbling N2 gas through the solution for 10 min. The vial was capped and placed in an oil bath with stirring at 80° C. for 16 h. The cooled reaction mixture was concentrated to dryness, then diluted with water (5 mL) and ethyl acetate (15 mL). The aqueous layer was extracted with ethyl acetate (2×5 mL) and the combined organic extracts were dried (Na2SO4), filtered and concentrated under a stream of N2 gas. The residue was purified by flash chromatography on silica gel (35 g) utilizing 9:1 dichloromethane/acetone as eluent. Fractions pure by TLC were combined and concentrated to give 139 mg (51%) of [4-(3′-chloro-6-methoxy-biphenyl-3-ylmethyl)-phenyl]-urea (P-378) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 3.74 (s, 3H), 3.83 (s, 2H), 5.75 (br s, 2H), 7.03 (d, J=8.4 Hz, 1H), 7.08 (m, 2H), 7.15 (d, J=2.4 Hz, 1H), 7.18 (dd, J=8.4, 2.4 Hz, 1H), 7.28 (m, 2H), 7.36-7.41 (m, 3H), 7.48 (m, 1H), 8.40 (br s, 1H) ppm. MS (APCI+): 367.0 (M++1); LC-MS: 95.9% purity.

Provenance & Evidence