Potassium Phosphate, Tribasic → HCID 22636992, compound

Participants

Reaction Steps

N-(4-Bromophenyl)-2,2,2-trifluoro-N-methyl-acetamide (1.32 g; 5.2 mmol), bis(pinacolato)diboron (1.57 g; 14.1 mmol), potassium acetate (1.38 g; 14.1 mmol) and 1,1′-bis(diphenylphosphino) ferrocene-dichloropalladium(II) (PdCl2(dppf)) (228 mg; 0.29 mmol) are stirred in dimethoxyethane (47 ml; dried over a molecular sieve) at a bath temperature of 80° C. for 17 hours while gassing with argon. After cooling to room temperature, bis(pinacolato)diboron (250 mg; 0.995 mmol) and bis(diphenylphosphino)ferrocene-dichloropalladium(II) (PdCl2(dppf)) (31 mg; 0.039 mmol) are added again and the mixture is stirred again for 1 hour at a bath temperature of 80° C. under argon. After cooling to room temperature, dimethylformarnide (95 ml), tetrakis-triphenylphosphine-palladium (416 mg; 0.36 mmol), 5-(3,5-diethoxy-4-iodo-benzyl)-pyrimidine-2,4-diamine (example 1) (1.56 g; 3.76 mmol) and a 2 M aqueous potassium phosphate solution (18.8 ml) are added. The reaction mixture is stirred for 7 hours at 80° C., cooled to room temperature and concentrated. Water (300 ml) is added to the residue and the product which has precipitated out is filtered off with suction. The tacky filter cake is dissolved in methanol and the solution is evaporated. Azeotropic distillation is carried out twice with methanol and the substance is dried under a high vacuum. The crude product obtained is chromatographed twice over silica gel (125 g) with methylene chloride/methanol/NH4OH conc. 19/110.05. The pure fractions are combined, the solvent is concentrated, the residue is stirred with methanol (10 ml), filtered off with suction and dried under a high vacuum. 570 mg (26%) 5-(2,6-diethoxy-4′-methylamino-biphenyl-4-ylmethyl)-pyrimidine-2,4-diamine are obtained as a light-yellow powder.

Provenance & Evidence