Reaction #168206

Reaction equation

2,6-dichloro-4-(4-phenoxyphenyl)nicotinonitrile

3-acetamidophenylboronic acid

potassium phosphate tribasic monohydrate

→

N-(3-(6-chloro-5-cyano-4-(4-phenoxyphenyl)pyridin-2-yl)phenyl)acetamide

Yield 42.7%

Solvents

N,N-dimethylformamide

ethyl acetate

Conditions

Workup

1. 1
   TemperatureAfter cooling to room temperature
2. 2
   Washwashed with water (10 mL), brine (10 mL)
3. 3
   Dryingdried (MgSO4)
4. 4
   Concentrationconcentrated
5. 5
   WashSilica gel chromatography, eluting with 5-40% ethyl acetate in hexanes

Procedure

A mixture of 2,6-dichloro-4-(4-phenoxyphenyl)nicotinonitrile (51 mg, 0.149 mmol, from Step 2 of Example 8), 3-acetamidophenylboronic acid (29.4 mg, 0.164 mmol), palladium tetrakis(triphenylphosphine) (15.12 mg, 0.015 mmol) and potassium phosphate tribasic monohydrate (0.299 mL, 0.598 mmol) in N,N-dimethylformamide (1.5 mL) was heated to 90° C. under nitrogen for 2 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (80 mL), washed with water (10 mL), brine (10 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 5-40% ethyl acetate in hexanes, gave N-(3-(6-chloro-5-cyano-4-(4-phenoxyphenyl)pyridin-2-yl)phenyl)acetamide as white solid (28 mg, 42% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.26 (1H, s), 7.79-7.89 (1H, m), 7.77 (1H, s), 7.67-7.73 (1H, m), 7.58-7.66 (2H, m), 7.50-7.57 (1H, m), 7.37-7.47 (3H, m), 7.17-7.24 (1H, m), 7.05-7.16 (4H, m), 2.22 (3H, s); MS (ES+) m/z: 440 (M±H); LC retention time: 4.165 min (analytical HPLC Method A).

Source