4-AMINO-2,6-DIFLUOROPYRIDINE

In a 500 mL autoclave, 49.8 g (0.25 mol) of 2, 6-difluoro-3, 5-dichloro-4-aminopyridine, 200mL ethanol, 5.61 g (0.55 mol) of triethylamine, 10.0 g of 10percent palladium on carbon, Keep the temperature at 25 , Filled with hydrogen pressure 0.46 MPa, Reaction for 24 hours.After cooling, the hydrogen was released, suction filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate = 3: 1)20.6 g of 2, 6-difluoro-4-aminopyridine was obtained as a white solid, Liquid normalized content of 99.7percent, yield 63.5percent.4-Amino-3-chloro-2, 6-difluoropyridine (6) and 4-amino-2, 6-difluoropyridine (7). A suspension of 19.9 g (100 mmol) of 5, 2.2 g of 10percent Pd/C and 27 mL (190 mmol) of triethylamine in 100 mL of anhydrous ethanol was hydrogenated at 50 psi in a Parr hydrogenation apparatus overnight (about 18 h). The catalyst was filtered and carefully washed with ethanol. The combined filtrate and washings were evaporated to dryness in vacuo. The residue was partitioned between ether and water, and the water layer was extracted with ether. The combined ether layers were dried (MgSO4) and concentrated to dryness. The residue was dissolved in ethanol and the solution was treated with 50 g of silica gel. The solvent was removed in vacuo to give a powder, which was purified by silica gel column chromatography, eluted with CH2Cl2 to afford 9.4 g (57percent) of 6 and 4.3 g (33percent) of 7. [0129] Compound 6 was isolated as a white solid: mp 8485° C.; TLC, Rf 0.55 (CH2Cl2); 1H NMR (CDCl3) δ 5.15 (br s, 2H, NH2, D2O exchangeable), 6.20 (s, 1H, 5-H). Analysis calculated for C5H3ClF2N2: C, 36.49; H, 1.84; N, 17.02. Found: C, 36.78; H, 2.09; N, 16.89. [0130] Compound 7 was isolated as a white solid: mp 126-128° C. (Lit., Secrist, et al., J. Med. Chem. 1988 31, 405-410 mp 125-127° C.); TLC, Rf 0.37 (CH2Cl2); 1H NMR (DMSO-d6) δ 6.00 (s, 2H, 3- and 5-H), 6.70 (br s, 2H, NH2, D2O exchangeable). Analysis calculated for C5H4F2N2: C, 46.16; H, 3.10; N, 21.54. Found: C, 46.01; H, 3.39; N, 21.29.Anhydrous F (300 mg, 5. 16 mmol) was added to a mixture of 1 (700 mg, 1.72 mmol) and kryptofix (1.0 g, 2.65 mmol) in DM SO (2.5 mL) and the mixture was stirred at 160 °C for 72 h. After the reaction, water was added and the solid formed was filtered and dried. The solid was dissolved in ethyl acetate (25.0 mL) and washed with water and dried (NaIn a 500 mL autoclave, 49.8 g (0.25 mol) of 2, 6-difluoro-3, 5-dichloro-4-aminopyridine, 200mL ethanol, 5.61 g (0.55 mol) of triethylamine, 10.0 g of 10percent palladium on carbon, Keep the temperature at 25 , Filled with hydrogen pressure 0.46 MPa, Reaction for 24 hours.After cooling, the hydrogen was released, suction filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate = 3: 1)20.6 g of 2, 6-difluoro-4-aminopyridine was obtained as a white solid, Liquid normalized content of 99.7percent, yield 63.5percent.4-Amino-3-chloro-2, 6-difluoropyridine (6) and 4-amino-2, 6-difluoropyridine (7). A suspension of 19.9 g (100 mmol) of 5, 2.2 g of 10percent Pd/C and 27 mL (190 mmol) of triethylamine in 100 mL of anhydrous ethanol was hydrogenated at 50 psi in a Parr hydrogenation apparatus overnight (about 18 h). The catalyst was filtered and carefully washed with ethanol. The combined filtrate and washings were evaporated to dryness in vacuo. The residue was partitioned between ether and water, and the water layer was extracted with ether. The combined ether layers were dried (MgSO4) and concentrated to dryness. The residue was dissolved in ethanol and the solution was treated with 50 g of silica gel. The solvent was removed in vacuo to give a powder, which was purified by silica gel column chromatography, eluted with CH2Cl2 to afford 9.4 g (57percent) of 6 and 4.3 g (33percent) of 7. [0129] Compound 6 was isolated as a white solid: mp 8485° C.; TLC, Rf 0.55 (CH2Cl2); 1H NMR (CDCl3) δ 5.15 (br s, 2H, NH2, D2O exchangeable), 6.20 (s, 1H, 5-H). Analysis calculated for C5H3ClF2N2: C, 36.49; H, 1.84; N, 17.02. Found: C, 36.78; H, 2.09; N, 16.89. [0130] Compound 7 was isolated as a white solid: mp 126-128° C. (Lit., Secrist, et al., J. Med. Chem. 1988 31, 405-410 mp 125-127° C.); TLC, Rf 0.37 (CH2Cl2); 1H NMR (DMSO-d6) δ 6.00 (s, 2H, 3- and 5-H), 6.70 (br s, 2H, NH2, D2O exchangeable). Analysis calculated for C5H4F2N2: C, 46.16; H, 3.10; N, 21.54. Found: C, 46.01; H, 3.39; N, 21.29.Anhydrous F (300 mg, 5. 16 mmol) was added to a mixture of 1 (700 mg, 1.72 mmol) and kryptofix (1.0 g, 2.65 mmol) in DM SO (2.5 mL) and the mixture was stirred at 160 °C for 72 h. After the reaction, water was added and the solid formed was filtered and dried. The solid was dissolved in ethyl acetate (25.0 mL) and washed with water and dried (Na4-Amino-3-chloro-2, 6-difluoropyridine (6) and 4-amino-2, 6-difluoropyridine (7). A suspension of 19.9 g (100 mmol) of 5, 2.2 g of 10% Pd/C and 27 mL (190 mmol) of triethylamine in 100 mL of anhydrous ethanol was hydrogenated at 50 psi in a Parr hydrogenation apparatus overnight (about 18 h). The catalyst was filtered and carefully washed with ethanol. The combined filtrate and washings were evaporated to dryness in vacuo. The residue was partitioned between ether and water, and the water layer was extracted with ether. The combined ether layers were dried (MgSO4) and concentrated to dryness. The residue was dissolved in ethanol and the solution was treated with 50 g of silica gel. The solvent was removed in vacuo to give a powder, which was purified by silica gel column chromatography, eluted with CH2Cl2 to afford 9.4 g (57%) of 6 and 4.3 g (33%) of 7. [0129] Compound 6 was isolated as a white solid: mp 8485 C.; TLC, Rf 0.55 (CH2Cl2); 1H NMR (CDCl3) delta 5.15 (br s, 2H, NH2, D2O exchangeable), 6.20 (s, 1H, 5-H). Analysis calculated for C5H3ClF2N2: C, 36.49; H, 1.84; N, 17.02. Found: C, 36.78; H, 2.09; N, 16.89. [0130] Compound 7 was isolated as a white solid: mp 126-128 C. (Lit., Secrist, et al., J. Med. Chem. 1988 31, 405-410 mp 125-127 C.); TLC, Rf 0.37 (CH2Cl2); 1H NMR (DMSO-d6) delta 6.00 (s, 2H, 3- and 5-H), 6.70 (br s, 2H, NH2, D2O exchangeable). Analysis calculated for C5H4F2N2: C, 46.16; H, 3.10; N, 21.54. Found: C, 46.01; H, 3.39; N, 21.29.Xantphos (1.2 g, 2.0 mmol), tris(dibenzylideneacetone)dipalladium (0.9 g, 1.0 mmol), cesium carbonate (6.4 g, 19.7 mmol), and

Molecular Weight:130.10
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:130.03425446
Monoisotopic Mass:130.03425446
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:89
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes