(2-((2,5-Dichloropyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide Chemical Properties

Boiling point:

527.5±50.0 °C(Predicted)

Density 

1.41±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

0.30±0.10(Predicted)

Appearance

Off-white to light yellow Solid

InChI

InChI=1S/C12H12Cl2N3OP/c1-19(2,18)10-6-4-3-5-9(10)16-11-8(13)7-15-12(14)17-11/h3-7H,1-2H3,(H,15,16,17)

InChIKey

XIKUAKVCJMVXCI-UHFFFAOYSA-N

SMILES

C1(Cl)=NC=C(Cl)C(NC2=CC=CC=C2P(C)(C)=O)=N1

(2-((2,5-Dichloropyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide Usage And Synthesis

Description

(2-((2,5-Dichloropyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide is a pharmaceutical intermediate compound used in the synthesis of the antitumour agent Brigatinib. Brigatinib is an orally administered, potent, selective anaplastic lymphoma kinase ( Brigatinib is an oral, potent, selective anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor approved for the treatment of adult patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have not received prior ALK inhibitor therapy.

Uses

(2-((2,5-Dichloropyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide is an intermediate of AP26113 which is a kind of effective ALK inhibitor.

Synthesis

25 mL of a one-necked flask was added DMF (3 mL), 2,5,6-trichloro pyrimidine (0.72 g, 3.9 mmol) was added successively with stirring,2- (dimethylphosphonino) aniline (0.5 g, 3 mmol)Anhydrous potassium carbonate (0.62 g, 4.5 mmol), heated to 60 ° C and stirred for 4 h.(30 mL x 2), the organic phase was combined, washed with water (60 mL x 2), and the organic layer was dried over anhydrous sodium sulfate, and the organic layer was washed with ethyl acetate (30 mL) and water (30 mL) Filtered and concentrated, and the residue was passed through a silica gel column to give 0.8 g of a pale yellow solid (2-((2,5-Dichloropyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide.

References

[1] Patent: CN106188138, 2016, A. Location in patent: Paragraph 0094-0096; 0106; 0107
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 10, p. 4948 - 4964
[3] Patent: EP3381925, 2018, A1. Location in patent: Paragraph 0158
[4] Patent: CN105330698, 2016, A. Location in patent: Paragraph 0196; 0197; 0198; 0199
[5] Patent: WO2012/151561, 2012, A1. Location in patent: Page/Page column 37-38

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