Potassium Phosphate, Tribasic → HCID 22636992, compound

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.

1. customdried over a molecular sieve) at a bath temperature of 80° C. for 17 hours
2. temperatureAfter cooling to room temperature
3. stirringThe reaction mixture is stirred for 7 hours at 80° C.
4. temperaturecooled to room temperature
5. concentrationconcentrated
6. additionWater (300 ml) is added to the residue
7. customthe product which has precipitated out
8. filtrationis filtered off with suction
9. dissolutionThe tacky filter cake is dissolved in methanol
10. customthe solution is evaporated
11. distillationAzeotropic distillation
12. customthe substance is dried under a high vacuum
13. customThe crude product obtained
14. customis chromatographed twice over silica gel (125 g) with methylene chloride/methanol/NH4OH conc. 19/110.05
15. concentrationthe solvent is concentrated
16. stirringthe residue is stirred with methanol (10 ml)
17. filtrationfiltered off with suction
18. customdried under a high vacuum

ORD record

ord-64478572ecd04f12a428f96f2a2f403a

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06821980B1