LCL-161

LCL161 has been used in trials studying the treatment of Leukemia, Neoplasms, Solid Tumors, Breast Cancer, and Ovarian Cancer, among others.

B6 to B7 (Compound (I))Charge a 2 L Argonaut reactor with 12O g (20 mmol) of crude B6 in 360.8 g (400 mL) of ethyl acetate. Heat the solution to 45 +/- 3B6 to B7 (Compound (I))Charge a 2 L Argonaut reactor with 12O g (20 mmol) of crude B6 in 360.8 g (400 mL) of ethyl acetate. Heat the solution to 45 +/- 30C , slowly add 109.1 g (120 mL) of HCI (5-6 N) in isopropyl alcohol while maintainingtemperature at 45 +/- 30C over 30 min. Stir and hold at 45 +/- 3 0C for 2 h. Take a sample for Process Steering Control. If PSC passes, cool the reaction mixture to 18 +/- 3 0C. Slowly add this solution to a 2 L Argonaut reactor containing 82.9 g of potassium carbonate in 500 g of water while maintaining the temperature at 5 +/- 30C. Stir at 5 +/- 3C for 30 min, add 451 g (500 mL )of ethyl acetate. Warm the solution to 20 +/- 3C and hold at this temperature for 1 h. Separate the two layers. Keep the top layer since B7 is in this organic phase. Wash the organic layer with 286.6 g (250 mL) of brine. Separate the bottom layer (aqueous).Concentrate the top organic layer to 500 mL under vacuum at 300C. Slowly add 1368 g (2 L) of heptanes while maintaining the temperature at 30 +/- 3 0C. Cool the suspension to 18 +/- 3 0C and hold at 18 +/- 3 0C for 1 h. Filter the solids and wash the solids with 136 g ( 200 mL) of heptanes containing octastat. Dry the solids in an oven at 45 0C for 16 h to give 80 g of B7 in 80% yield.The preferred compounds are selected from the group consisting of: (S)-N-((S)-1-Cyclohexyl-2-{(S)-2-[4-(4-fluoro-benzoyl)-thiazol-2-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-2-methylamino-propionamide; (S)-N-[(S)-Cyclohexyl-(ethyl-{(S)-1-[5-(4-fluoro-benzoyl)-pyridin-3-yl]-propyl}carbamoyl)-methyl]-2-methylamino-propionamide; (S)-N-((S)-1-Cyclohexyl-2-{(S)-2-[5-(4-fluoro-phenoxy)-pyridin-3-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-2-methylamino-propionamide; and N-[1-Cyclohexyl-2-(2-{2-[(4-fluorophenyl)-methyl-amino]-pyridin-4-yl}pyrrolidin-1-yl)-2-oxo-ethyl]-2-methylamino-propinamide;

Molecular Weight:500.6
XLogP3:4.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:8
Exact Mass:500.22574026
Monoisotopic Mass:500.22574026
Topological Polar Surface Area:120
Heavy Atom Count:35
Complexity:757
Defined Atom Stereocenter Count:3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes