4-Pyrimidinamine, 2,5-dichloro-N-[2-[(1-methylethyl)sulfonyl]phenyl]- Chemical Properties

Melting point:

149.0 to 153.0 °C

Boiling point:

538℃

Density 

1.436

Flash point:

279℃

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

form 

powder to crystal

pka

-0.03±0.10(Predicted)

color 

White to Light yellow

InChI

InChI=1S/C13H13Cl2N3O2S/c1-8(2)21(19,20)11-6-4-3-5-10(11)17-12-9(14)7-16-13(15)18-12/h3-8H,1-2H3,(H,16,17,18)

InChIKey

WWVLDJAVSQZSKO-UHFFFAOYSA-N

SMILES

C1(Cl)=NC=C(Cl)C(NC2=CC=CC=C2S(C(C)C)(=O)=O)=N1

Safety Information

HS Code 

2933.59.8000

4-Pyrimidinamine, 2,5-dichloro-N-[2-[(1-methylethyl)sulfonyl]phenyl]- Usage And Synthesis

Uses

2,5-Dichloro-N-[2-(isopropylsulfonyl)phenyl]pyrimidin-4-amine is used as a reagent in the synthesis of potent and selective anaplastic lymphoma kinase (ALK-5) inhibitors, used as an anti-tumor treatment.

Synthesis

To a flask containing 40 g (0.200 mol) 2-(isopropylsulfonyl)aniline (Formula-XI) in 400 mL of toluene solution under nitrogen protection were added 49.7 g (0.27 mol) 2,4,5-trichloropyrimidine (Formula-XII), 81.7 g (0.25 mol) cesium carbonate, 4.5 g (0.02 mol) palladium(II) acetate, and 13.1 g (0.05 mol) triphenylphosphine. The reaction mixture was heated to reflux under nitrogen atmosphere and maintained for 4 hours. The reaction was monitored by thin layer chromatography (TLC) to confirm that 2-(isopropylsulfonyl)aniline was completely consumed. Upon completion of the reaction, the mixture was cooled to 25-30 °C and filtered. The solids were washed with 400 mL of ethyl acetate. The filtrate and washings were combined and the crude product was obtained by removing toluene and ethyl acetate by distillation under reduced pressure at 60 °C. The crude product was purified by column chromatography to afford 45.6 g of 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidin-4-amine (formula-XIII) as a light yellow solid in 65.6% (theoretical) yield.

References

[1] European Journal of Medicinal Chemistry, 2017, vol. 136, p. 497 - 510
[2] Patent: WO2017/158619, 2017, A1. Location in patent: Page/Page column 19
[3] Patent: EP2990405, 2016, A1. Location in patent: Paragraph 0097; 0120; 0121
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 14, p. 5675 - 5690
[5] European Journal of Medicinal Chemistry, 2016, vol. 123, p. 80 - 89

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