Benzonitrile, 4-bromo- → 4'-(2,4-Diamino-pyrimidin-5-ylmethyl)-2',6'-diethoxy-biphenyl-4-carbonitrile

Participants

Reaction Steps

4-Bromo-benzonitrile (186 mg; 1 mmol), bis(pinacolato)diboron (279 mg; 1.1 mmol), potassium acetate (294 mg; 3 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-dichloropalladium(II) (PdCl2(dppf)) (46 mg; 0.06 mmol) are stirred in dimethylformamide (6 ml; dried over a molecular sieve) at a bath temperature of 80° C. for 3 hours while gassing with argon. After cooling to room temperature, dimethylformamide (20 ml; dried over a molecular sieve), tetrakis-triphenylphosphine-palladium (90 mg; 0.078 mmol), 5-(3,5-diethoxy-4-iodo-benzyl)-pyrimidine-2,4-diamine (example 1) (331 mg; 0.8 mmol) and a 2 M aqueous potassium phosphate solution (4 ml) are added. The reaction mixture is stirred for approx. 1.5 hours at 80° C., cooled to room temperature and concentrated. The residue obtained is chromatographed over silica gel (100 g) with methylene chloride/methanol/NH4OH (19/1/0.05)0.61 mg (20%) 4′-(2,4-diamino-pyrimidin-5-ylmethyl)-2′,6′-diethoxy-biphenyl-4-carbonitrile are obtained as a beige powder.

Provenance & Evidence