1-(6-Chloro-pyridazino-3-yl)piperidine

General procedure: To a solution of absolute ethanol (5 mL) and dichlorodiazine (3.36 mmol) in a 50mL round-bottom flaskwas added triethylamine (5.03 mmol), followed by the amine (5.03 mmol). The mixture was stirred either under reflux of ethanol (for dichloropyridazine and for dichloropyrazine) or at room temperature (for dichloropyrimidines). The reaction was monitored by GC. Once the starting dichlorodiazinewas completely consumed, the mixture was poured into a saturated NH4Cl solution (20 mL), then extracted with CH2Cl2 (320 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under vacuum. The crude solid was triturated in petroleum ether, filtered through a Buchner to afford the pure product.To a solution of 3, 6-dichloropyridazine (55)(0.3 g, 2.0 mmol) in DMF (20 mL) was addedN, N-diisopropylethylamine (377 µL, 2.2 mmol) and piperidine (200 µL, 2.0 mmol). The mixture was heated at reflux for 17 h and after cooling to room temperature, partitioned between ethyl acetate (100 mL) and HGeneral procedure: A suspension of the appropriate amide (1.0 mmol) and pyridine-3-boronic acid (1.1 mmol) were suspended in acetonitrile-aqueous sodium carbonate (1:1, 0.4 M, 10 mL) and deoxygenated with bubbling argon at ambient temperature. A catalytic amount of Pd(PPh3)4(0.05 mmol, 5 mol%) was added, and the mixture heated at reflux for 18 h. The reaction was partitioned between ethyl acetate (30 mL) and saturated aqueous sodium carbonate (30 mL), the layers separated, and the aqueous layer extracted with ethyl acetate (2 × 30 mL). The combined organic extracts were washed with brine (40 mL), dried (MgSO4), filtered, and the solvent evaporated under reduced pressure to give the crude product.S-Chloro-beta-pipehdin-i-ylpyhdazine (112 mg, 0.56 mmol) and 2M Na2CO3 (2.2 ml, 4.4 mmol) were added to a solution of 1-{3-[7-(4, 4, 5, 5-tetramethyl-[1 , 3, 2]dioxaborolan-2-yl)- imidazo[1 , 2-a]pyhdin-3-yl]-phenyl}-3-(2, 2, 2-trifluoro-ethyl)-urea (200 mg, 0.43 mmol) in DME(2.5 ml) [reaction degassed by bubbling through nitrogen], followed by tetrakis(triphenylphosphine)palladium (0) (50 mg, 0.04 mmol). The reaction was heated to9O0C for 4 h, before being partitioned between water and EtOAc. The organic fraction was dried (MgSO4), filtered and concentrated in vacuo and the residue was purified by preparative HPLC to generate the product (50 mg). MS: [M+H]+ = 496

Molecular Weight:197.66
XLogP3:2.1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:197.0719751
Monoisotopic Mass:197.0719751
Topological Polar Surface Area:29
Heavy Atom Count:13
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes