1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine Chemical Properties

Boiling point:

421.2±45.0 °C(Predicted)

Density 

1.072±0.06 g/cm3(Predicted)

storage temp. 

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

pka

9.21±0.10(Predicted)

Appearance

White to off-white Solid

InChI

InChI=1S/C19H27ClN2/c1-19(2)8-7-16(14-22-11-9-21-10-12-22)18(13-19)15-3-5-17(20)6-4-15/h3-6,21H,7-14H2,1-2H3

InChIKey

YCNNHDUZLQPKJY-UHFFFAOYSA-N

SMILES

N1(CC2CCC(C)(C)CC=2C2=CC=C(Cl)C=C2)CCNCC1

1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine Usage And Synthesis

Uses

1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine is an intermediate of Venetoclax (ABT-199) which is a small, oral chemical molecule used for the treatment of chronic lymphocytic leukemia (CLL) associated with a specific chromosomal abnormality.

Synthesis

The general procedure for the synthesis of 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carboxylic acid tert-butyl ester as 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine was carried out as follows: at 0 °C, 4 M hydrochloric acid of an ethyl acetate solution (4 mL) was slowly added to a dichloromethane solution (15 mL) of compound 19 (0.6 g, 1.44 mmol). The reaction mixture was continued to be stirred at room temperature for 3 hours. Upon completion of the reaction, the reaction mixture was filtered, the filter cake was dissolved with water and neutralized with potassium phosphate. Subsequently, extraction was carried out with ethyl acetate (30 mL x 2). The organic phases were combined and dried with anhydrous sodium sulfate. Finally, the solvent was removed under reduced pressure to give 0.4 g of the target product in 87% yield.

References

[1] Patent: CN108658983, 2018, A. Location in patent: Paragraph 0153; 0156; 0163; 0164
[2] Patent: US2010/184766, 2010, A1. Location in patent: Page/Page column 51
[3] Patent: US2010/305122, 2010, A1. Location in patent: Page/Page column 119
[4] Patent: WO2011/150016, 2011, A1. Location in patent: Page/Page column 79
[5] Patent: WO2012/71336, 2012, A1. Location in patent: Page/Page column 10

1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine(1228780-72-0)Related Product Information

• 1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine dihydrochloride
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