CEP 33779

CEP-33779 is a novel, selective, and orally bioavailable inhibitor of JAK2 with an IC50 of 1.8±0.6 nM.

To an oven dried tube is added palladium acetate (about 10 mg) and 2, 2’-bis-dicyclohexylphosphanylbiphenyl(about 30 mg), 8-(4-methanesulfonyl-phenyl)-[1, 2, 4]triazolo[1, 5-a]pyridin-2-ylamine (about 75 mg), 1-(3-bromo-phenyl)-4-methylpiperazine (about 80 mg), a suitable base, such as cesium carbonate (about 270 mg) anda suitable solvent, such as 1, 4-dioxane (about 5 mL). The tube is evacuated and backflushed with nitrogen threetimes. The tube is sealed and heated at about 80°C for about 72 hours. The mixture is cooled to room temperatureand the product isolated in a suitable manner. For example, the cooled mixture may be diluted with dichloromethane(about 10 mL), filtered through a plug of diatomaceous earth, rinsed with dichloromethane and evaporated. Thematerial may then be purified, e.g., via chromatography, e.g., utilizing an ISCO automated purification apparatus(e.g., amine modified silica gel column 5percent→100percent ethyl acetate in hexanes). [8-(4-Methanesulfonyl-phenyl)-[1, 2, 4]triazolo[1, 5-a]pyridin-2-yl]-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine (i.e., COMPOUND A) is isolated as a yellowsolid (about 0.07 g). MP = 232-234 °C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.49 (d, J=7.2 Hz, 1H), 8.25 (d, J=7.5Hz, 2H), 8.08 (d, J=7.9 Hz, 2H), 7.65 (d, J=7.7 Hz, 1H), 7.38 (s, 1H), 7.27-7.20 (m, 1H), 7.04-6.95 (m, 2H), 6.84 (s, 1H), 6.60 (d, J=8.0 Hz, 1H), 3.30-3.25 (m, 4H), 3.10 (s, 3H), 2.63-2.58 (m, 4H), 2.38 (s, 3H). MS = 463 (MH)+

Molecular Weight:462.6
XLogP3:3.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:5
Exact Mass:462.18379527
Monoisotopic Mass:462.18379527
Topological Polar Surface Area:91.2
Heavy Atom Count:33
Complexity:745
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes