1H-1,2,3-TRIAZOLO[4,5-C]PYRIDINE

3, 4-diaminopyridine (2.0 g, 0.048 mol) was dissolved in a 2N hydrogen chloride aqueous solution (25 mL), cooled to 0 ° C, Sodium nitrite (1.9 g, 0.027 mol) was dissolved in distilled water (3 mL) and added slowly, And stirred for 1 hour. The resulting solid was filtered and washed with distilled water to give the title compound im-7-a (1.96 g, 89percent) as a yellow solid.3, 4-diaminopyridine (2.0 g, 0.048 mol) was dissolved in a 2N hydrogen chloride aqueous solution (25 mL), cooled to 0 C, Sodium nitrite (1.9 g, 0.027 mol) was dissolved in distilled water (3 mL) and added slowly, And stirred for 1 hour. The resulting solid was filtered and washed with distilled water to give the title compound im-7-a (1.96 g, 89%) as a yellow solid. (3.5 g, 18.14 mmol) was added to a mixture of 2, 3-dichloro-5-nitropyri- dine (2.18 g, 18.14 mmol) and potassium carbonate (7.5 g, 54.41 mmol) in acetonitrile (50 mE). The mixture was stirred at rt for 12 h. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give the crude product as a yellow solid. The crude product was purified by column chromatography over silica gel (petroleum ether/ethyl acetate=1 00:0 to petroleum ether/ethyl acetate=70:30). The pure fractions were collected and the solvent was concentrated under reduced pressure to give the product as a yellow solid (4.2 g, 83.7%). Iron (2.02 g, 36.1 mmol) and ammonium chloride (1.93 g, 36.1 mmol) were added to a mixture of 2-(3-chloro- 5-nitropyridin-2-yl)-2H-[1 , 2, 3]triazolo[4, 5-b]pyridine and3-(3-chloro-5-nitropyridin-2-yl)-3H-[1 , 2, 3]triazolo[4, 5-b] pyridine (4.0 g, 7.23 mmol) in THF (40 mE), water (10 mE) and methanol (20 mE). The reaction was stirred at 80 C. for 2 h. The reaction mixture was filtered though a pad of diatomaceous earth and the pad was washed with EtOAc (20 mEx3). The combined filtrates were concentrated to dryness to give crude product as a brown solid. The crude product was purified by flash column chromatography over silica gel (eluent: petroleum ether/ethyl acetate from 10:1 to 1:1). The desired fractions were collected and the solvent was concentrated under reduced pressure to afford the product as a brown oil (3.2 g, 86.1%). P0C13 (239 mg, 1.56 mmol) was added to a mixture of 6-(2H-[ 1 , 2, 3]triazolo[4, 5-b]pyridin-2-yl)-5-chloro- pyridin-3-amine and 6-(3H-[1 , 2, 3]triazolo[4, 5-b]pyridin-3- yl)-5-chioropyridin-3-amine (200 mg, 0.39 mmol), 1 -(quinolin-5-yl)-5-(trifluoromethyl)-1 H-pyrazole-4-car- boxylic acid, 3b (143.5 mg, 0.47 mmol), and pyridine (185 mg, 2.34 mmol) in dichloromethane (8 mE). The reaction mixture was stirred at 20 C. for 4 h. Sat. NaHCO3 solution (10 mE) was added to the mixture. The mixture was extracted with dichioromethane (20 mEx3). The organic layers were concentrated under reduced pressure to afford a crude product, which was purified by reverse phase HPEC (35% to 65% (v/v) CH3CN and H20 with 0.05% HC1) to afford N-(6-(2H-[1 , 2, 3]triazolo[4, 5-b]pyridin-2-yl)-5-chlo- ropyridin-3-yl)-1 -(quinolin-5-yl)-5-(trifluoromethyl)-1 Hpyrazole-4-carboxamide, Cpd 164 (35.7, 16.9%). 'H NMR (400 MHz, DMSO-d5) oe ppm 11.44 (s, 1H), 9.06 (br s, 1H), 8.98 (s, 1H), 8.84 (br d, J=3.7 Hz, 1H), 8.78 (s, 1H), 8.63 (s, 1H), 8.35 (br dd, J=8.2, 16.5 Hz, 2H), 8.01-7.88 (m, 2H), 7.76-7.59 (m, 3H). EC-MS: (ES, m/z): [M+1] 535.9; and11756] N-(6-(3H-[1 , 2, 3]triazolo[4, 5-b]pyridin-3-yl)-5- chioropyridin-3-yl)-1 -(quinolin-5-yl)-5-(trifluoromethyl)- 1H-pyrazole-4-carboxamide, Cpd 165 (21 mg, 9.6%). 'H NMR (400 MHz, DMSO-d5) oe ppm 11.51 (s, 1H), 9.08 (dd, J=2.2, 3.5 Hz, 1H), 9.02 (d, J=2.2 Hz, 1H), 8.84-8.75 (m, 3H), 8.68 (s, 1H), 8.35 (d, J=8.2 Hz, 1H), 8.02-7.94 (m, 2H), 7.73-7.68 (m, 2H), 7.64 (dd, J=4.6, 8.4 Hz, 1H). EC-MS:(ES, mlz): [M+1] 535.9. (3.5 g, 18.14 mmol) was added to a mixture of 2, 3-dichloro-5-nitropyri- dine (2.18 g, 18.14 mmol) and potassium carbonate (7.5 g, 54.41 mmol) in acetonitrile (50 mE). The mixture was stirred at rt for 12 h. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give the crude product as a yellow solid. The crude product was purified by column chromatography over silica gel (petroleum ether/ethyl acetate=1 00:0 to petroleum ether/ethyl acetate=70:30). The pure fractions were collected and the solvent was concentrated under reduced pressure to give the product as a yellow solid (4.2 g, 83.7%). (3.5 g, 18.14 mmol) was added to a mixture of 2, 3-dichloro-5-nitropyri- dine (2.18 g, 18.14 mmol) and potassium carbonate (7.5 g, 54.41 mmol) in acetonitrile (50 mE). The mixture was stirred at rt for 12 h. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to give the crude product as a yellow solid. The crude product was purified by column chromatography over silica gel (petroleum ether/ethyl acetate=1 00:0 to petroleum ether/ethyl acetate=70:30). The pure fractions were collected and the solvent was concentrated under reduced pressure to give the product as a yellow solid (4.2 g, 83.7%). Iron (2.02 g, 36.1 mmol) and ammonium chloride (1.93 g, 36.1 mmol) were added to a mixture of 2-(3-chloro- 5-nitropyridin-2-yl)-2H-[1 , 2, 3]triazolo[4, 5-b]pyridine and3-(3-chloro-5-nitropyridin-2-yl)-3H-[1 , 2, 3]triazolo[4, 5-b] pyridine (4.0 g, 7.23 mmol) in THF (40 mE), water (10 mE) and methanol (20 mE). The reaction was stirred at 80 C. for 2 h. The reaction mixture was filtered though a pad of diatomaceous earth and the pad was washed with EtOAc (20 mEx3). The combined filtrates were concentrated to dryness to give crude product as a brown solid. The crude product was purified by flash column chromatography over silica gel (eluent: petroleum ether/ethyl acetate from 10:1 to 1:1). The desired fractions were collected and the solvent was concentrated under reduced pressure to afford the product as a brown oil (3.2 g, 86.1%).The compound im-7-a (1.0 g, 8.3 mmol) was dissolved in methanol (60 mL), and Pd / C (10 wt%, 2.0 g) and concentrated hydrochloric acid (1 mL) Is added and reacted under hydrogen pressure (75 psi) for 7 hours. The catalyst of the reaction mixture was filtered off using celite, and the filtrate was concentrated and dried under reduced pressure to give quantitative (1.38 g) of the title compound im-7 as a yellow solid.

Molecular Weight:120.11
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:120.043596145
Monoisotopic Mass:120.043596145
Topological Polar Surface Area:54.5
Heavy Atom Count:9
Complexity:105
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes