Methanol → HCID 66599387, compound

Participants

Reaction Conditions

Reaction Steps

5-Bromo-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)benzonitrile (100 mg, 0.250 mmol), Pd(Ph3P)4 (14.47 mg, 0.013 mmol), 2-methoxyphenylboronic acid (53.3 mg, 0.351 mmol), aqueous Na2CO3 (0.28 mL, 0.560 mmol), MeOH (0.5 mL) and Toluene (1 mL) were combined in a 2 ml microwave vial, sealed, the vial flushed with nitrogen and heated to 105° C. for 5 hrs in an oil bath. The reaction was poured into a separating funnel loaded with dichloromethane and 0.1 N aq. KOH. The aqueous layer was extracted one more time with dichloromethane, the organic layers combined and washed once with brine, then dried over MgSO4, filtered and concentrated in vacuum. Purification by chromatography on silica Solvent A: 500 ml ethyl acetate+500 ml CH2Cl2+10 ml Et3N; Solvent B: 500 ml ethyl acetate+500 ml CH2Cl2+10 ml Et3N+100 ml MeOH, Gradient from 100% A to 100% B, product elutes at ˜25% Solvent B. Combine product containing fractions and evaporate volatiles. 90.1 mg 2′-methoxy-4-(4-(4-methylpiperazine-1-carbonyl)phenylamino)-biphenyl-3-carbonitrile were isolated as a colorless film. MS (ESI) m/z 427 (M+H). 1H NMR (CDCl3) δ ppm 7.74 (d, 1H, J=2.2), 7.60 (dd, 1H, J=8.9, 1.9), 7.42 (d, 2H, J=8.5), 7.34 (d, 1H, J=8.9), 7.32 (dt, 1H, J=1.5, ˜8, ˜8), 7.26 (dd, 1H, J=1.6, ˜8), 7.20 (d, 2H, J=8.2), 7.02 (t, 1H, J=7.5), 6.98 (d, 1H, J=8.2), 6.49 (s, 1H), 3.83 (s, 3H), 3.85-3.45 (b, 4H), 2.43 (bs, 4H), 2.32 (s, 3H).

Provenance & Evidence