LCL-161 Chemical Properties

Boiling point:

713.7±60.0 °C(Predicted)

Density 

1.245±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

≥25.05 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH

form 

solid

pka

14.25±0.46(Predicted)

color 

White to yellow

InChIKey

UFPFGVNKHCLJJO-SSKFGXFMSA-N

SMILES

C(N[C@@H](C1CCCCC1)C(N1CCC[C@H]1C1=NC(C(=O)C2=CC=C(F)C=C2)=CS1)=O)(=O)[C@@H](NC)C

Safety Information

RIDADR 

3077

HS Code 

29341000

LCL-161 Usage And Synthesis

Description

LCL-161 is a small molecule Smac mimetic that inhibits multiple inhibitor of apoptosis (IAP) family proteins.

Uses

LCL 161 is a second mitochondria-derived activator of caspases (SMAC) inhibitor used to prolong patient survival by increasing apoptosis of anti-tumor drugs.

Synthesis

General procedure for the synthesis of (S)-N-((S)-1-cyclohexyl-2-((S)-2-(4-(4-fluorobenzoyl)thiazol-2-yl)pyrrolidin-1-yl)-2-oxoethyl)-2-(methylamino)propanamide from B6 to B7 (Compound (I)) using Compound (CAS:1005342-82-4) as a raw material. To a 2L Argonaut reactor containing 120 g (20 mmol) of crude B6 was added 360.8 g (400 mL) of ethyl acetate. The solution was heated to 45±3°C and 109.1 g (120 mL) of isopropanol solution of 5-6N HCl was slowly added while maintaining the temperature at 45±3°C for 30 min. Stirring was continued at 45±3°C for 2 hours. Samples were taken for process control analysis. If the process control analysis passed, the reaction mixture was cooled to 18±3°C. The solution was slowly added to another 2L Argonaut reactor, which was pre-filled with 500g of water and 82.9g of potassium carbonate, while controlling the temperature at 5 ± 3°C. After stirring at 5±3°C for 30 minutes, 451 g (500 mL) of ethyl acetate was added. The solution was warmed to 20±3°C and kept for 1 hour. The two layers were separated and the upper organic phase was retained as B7 was present in this phase. The organic layer was washed with 286.6 g (250 mL) of brine and the lower aqueous phase was discarded. The upper organic phase was concentrated under reduced pressure to 500 mL at 30 °C. 1368 g (2 L) of heptane was slowly added while maintaining the temperature at 30 ± 3 °C. The suspension was cooled to 18 °C and the temperature was set at 30 ± 3 °C. The suspension was cooled to 18±3°C and held for 1 hr. The solids were collected by filtration and washed with 136 g (200 mL) of simvastatin-containing heptane. The solid was dried in an oven at 45°C for 16 hours to give 80 g of B7 in 80% yield.

in vivo

References

[1] Patent: WO2011/18474, 2011, A1. Location in patent: Page/Page column 42

LCL-161(1005342-46-0)Related Product Information

• Everolimus
• 3-METHYLADENINE
• BV6
• Pictilisib
• Birinapant
• Olaparib