N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine

ASP-3026 is a member of the class of diamino-1,3,5-triazines that is 1,3,5-triazine-2,4-diamine in which the amino groups at positions 2 and 4 are respectively carrying 2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl and 2-(propan-2-ylsulfonyl)phenyl substituents. It is a potent inhibitor of anaplastic lymphoma kinase (ALK), Ack and ROS1 activity (IC50 values are 3.5, 5.8 and 8.9 nM respectively) and exhibits anti-cancer properties. It has a role as an antineoplastic agent, an apoptosis inducer, an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, an antimalarial and an EC 6.1.1.6 (lysine--tRNA ligase) inhibitor. It is a secondary amino compound, a monomethoxybenzene, a N-methylpiperazine, an aromatic amine, a diamino-1,3,5-triazine, a member of piperidines and a sulfone.|ASP3026 has been used in trials studying the treatment of Solid Tumor, B-Cell Lymphoma, Advanced Malignancies, Positive for Anaplastic Lymphoma Kinase, and Positive for Proto-Oncogene Tyrosine-Protein Kinase ROS.

Alternative method 2 for Step 7 A mixture of 5a(210 mg, 0.690 mmol) and MsOH (0.13 mL, 2.00 mmol) in EtOH (3 mL) was stirred at room temperature for 15 min. To this mixture was added 13a (170 mg, 0.543 mmol), and the reaction mixture was stirred at 100°C for 2 h. After the mixture was cooled to room temperature, water and saturated aqueous NaHCO3 solution were added. The resulting slurry was extracted with CHCl3, and the organic layer was dried overNa2SO4, then concentrated in vacuo. The residue was purifiedby silica gel column chromatography (CHCl3/MeOH/28percentaqueous NH3=50 : 1 : 0.1 to 30 : 1 : 0.1) to give 14a (180 mg, 57percent). 1H-NMR (400 MHz, CDCl3) δ: 1.31 (6H, d, J=6.8 Hz), 1.62–1.79 (2H, m), 1.90–2.02 (2H, m), 2.23–2.81 (11H, m), 2.30 (3H, s), 3.18–3.32 (1H, m), 3.63–3.75 (2H, m), 3.88 (3H, s), 6.45–6.62 (2H, m), 7.14–7.29 (1H, m), 7.43–7.71 (2H, m), 7.88(1H, dd, J=1.6, 8.0 Hz), 8.02–8.17 (1H, m), 8.27–8.61 (2H, m), 9.28 (1H, s). ESI-MS m/z: 581 [M+H]+. High resolution (HR)-MS (ESI) m/z: 581.3022 [M+H]+ (Calcd for C29H41N8O3S:581.3022).Step 5

Molecular Weight:580.7
XLogP3:4.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:11
Rotatable Bond Count:9
Exact Mass:580.29440834
Monoisotopic Mass:580.29440834
Topological Polar Surface Area:124
Heavy Atom Count:41
Complexity:904
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes