(5-CHLORO-PYRIDIN-2-YL)-HYDRAZINE

A solution of 2, 5-dichioropyridine (13a) (7.4 g, 50.0 mmol) and hydrazine hydrate(101 mL, 3250 mmol) in Pyridine (100 mL) was heated at reflux for 6 h and concentratedin vacuum to dryness. The residue obtained was dissolved in DCM (500 mL), washed with I N aqueous NaOH (500 mL), water (3 x 500 mL). The organic layer was dried over MgSO4 filtered and concentrated in vacuum to dryness to furnish 5-chloro-2- hydrazinylpyridine (13b) (2.95 g, 20.55 mniol, 41percent yield) as light yellow solid. ‘H NMR(300 MHz, DMSO-d6)ö 7.97 (d, .J= 2.5 Hz, IH), 7.67 (s, IH), 7.50 (dd, J= 9.0, 2.6 Hz, IH), 6.73 (dd, .J= 9.0. 0.6 Hz, IH), 4.17 (s, 2H); MS (ES+) 144.2 (M+I).Hydrazine hydrate(45 ml, 0.9 mol) and 2-PrOH (45 ml) were added to 2-bromo-5-chloropyridine (3) (22.43 g, 0.117 mol), and the mixturewas refluxed for 10 h. The solvent was evaporated underreduced pressure, the obtained residue was suspended inwater (50 ml), filtered, washed with ice water (2×20 ml), and air-dried. Yield 13.78 g (82percent), white crystals, mp 124–125° (MeOH) (mp 123–125° (benzene)11). Rf 0.45(EtOAc–CHCl3, 1:1). 1H NMR spectrum (CDCl3), δ, ppm(J, Hz): 3.81 (2, br. s, NH2); 5.88 (1, br. s, NH); 6.71(1, d, J = 8.8, H-3); 7.45 (1, dd, J = 8.8, J = 2.3, H-4);8.07 (1H, d, J = 2.3, H-6). 13C NMR spectrum (CDCl3), δ, ppm: 107.3; 118.9; 135.9; 144.4; 158.8.General procedure: To a solution of phenylhydrazine (182 muM, 200 mg, 1.849 mmole), ethyl benzoylacetate (382.9 mul, 426.5 mg, 2.219 mmole) in EtOH (0.5 ml) was added and stirred at 90 C overnight in a sealed tube. After cooling to room temperature, the solid obtained was filtered, washed with EtOH, and dried to afford 3 (112 mg, 26% yield) as a yellow solid.To 4.30 g (30.00 mmol) 5-chloro-2-hydrazinyl-pyridine in methanol (30 mL) 7.74 g (42.00 mmol) 2, 2, 2- trifluoro-ethanimidic acid ethyl ester was added, and the reaction mixture was stirred at room temperature over night. The solvent was evaporated and the residue was then stirred with n-hexane (30 mL) and ethyl acetate (3 mL). The brownish precipitate was separated and dried to obtain 4.81 g (purity: 89.0 %; yield: 59.8 %) N'-(5-chloropyridin-2-yl)(trifluoro)ethanehydrazonamide. Formula: C7H6CIF3N4 Molecular weight: 238.59 g/mol HPLC-MS (ESI Positiv): 239.0 (M+l); Rt = 0.91; 0.93 min (instrument: LC-MS7)General procedure: The corresponding2-hydrazinylpyridines 1a-f, g, h (1 mmol) was added to a mixture of dialkyl chloroacetylenephosphonate2a-c (1 mmol) and K2CO3 (1 mmol) in 5 mL of anhydrous acetonitrile at room temperature. The mixturewas stirred at room temperature until the starting chloroethynylphosphonate consumed (monitoring with 31PNMR). After the reaction was completed, the reaction mixture was filtered and evaporated. The oily residuewas chromatographed on SiO2 eluting with 1% MeOH in CHCl3General procedure: The corresponding2-hydrazinylpyridines 1a-f, g, h (1 mmol) was added to a mixture of dialkyl chloroacetylenephosphonate2a-c (1 mmol) and K2CO3 (1 mmol) in 5 mL of anhydrous acetonitrile at room temperature. The mixturewas stirred at room temperature until the starting chloroethynylphosphonate consumed (monitoring with 31PNMR). After the reaction was completed, the reaction mixture was filtered and evaporated. The oily residuewas chromatographed on SiO2 eluting with 1% MeOH in CHCl3

Molecular Weight:143.57
XLogP3:1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:143.0250249
Monoisotopic Mass:143.0250249
Topological Polar Surface Area:50.9
Heavy Atom Count:9
Complexity:88.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes