5-BROMO-2-HYDRAZINOPYRIDINE

2-Chloro-5-bromopyridine (64 g, 333 mmol) was suspended in hydrazine monohydrate (250 mL) and the mixture was heated at 70° C. for 72 hours. Preparation 23: (5 -Bromopyridin -2-yl)hydrazine; 2-Chloro-5-bromopyridine (64 g, 333 mmol) was suspended in h ydrazine monohydrate (250 ml_) and the mixture was heated at 70 °C for 72 hours. The reaction mixture was then diluted with water (750 mL) and the resulting precipitate was filtered off and azeotroped, firstly with toluene (x2) then dichloromethane (x2), to afford the title compound as a paie brown solid (52 g, 83percent).a) 5-Bromo-2-hydrazinylpyridine. A mixture of 5-bromo-2-chloropyridine (11.5 g, 60 mmol) and hydrazine hydrate (100 mL) was refluxed under Argon for 2 h. The mixture was cooled to room temperature, filtered and the solids were washed with water (50 mL x 3), dried to give the title compound (8.30 g, 74.4percent yield) as yellow solids. MS: m/z 188.0 [M+HEXAMPLE 13-(2-Methoxyphenyl)-6-(4-methoxyphenyl)-[l, 2, 4]triazolo[4, 3-a]pyridine a) 5-Bromo-2-hydrazinylpyridine. A mixture of 5-bromo-2-chloropyridine (11.5 g, 60 mmol) and hydrazine hydrate (100 mL) was refluxed under Argon for 2 h. The mixture was cooled to room temperature, filtered and the solids were washed with water (50 mL x 3), dried to give the title compound (8.30 g, 74.4percent yield) as yellow solids. MS: m/z 188.0 [M+H9.3 ml (9.5 g, 190.2 mmol) hydrazine hydrate are added to a solution of 1.8 g (9.5 mmol) 5-bromo-2-chloropyridine in 25 ml ethanol at RT, while stirring, and the mixture is then stirred at 90° C. for 46 h. After concentration of the reaction mixture in vacuo, the residue is stirred in water and the solid is filtered off, washed with water and diethyl ether and dried in vacuo.Yield: 0.8 g (44percent of th.)LC-MS (Method 8): RTo a solution of 5-bromo-2-fluoropyridine (1 Og, 56.8 mmol) in EtOH (120 ml) was added hydrazine hydrate (14.22 g, 284 mmol), the mixture was heated to reflux and stirred overnight (16hr).The solvent of the reaction mixture was evaporated about half under reduced pressure, then cooling in an ice bath there precipitation was ocurred, filtered and washed the product with a minimun of EtOH and water, dried in vacuum to obtain pure desired product as white powder (10.2g, yield 91 percent ).LCMS (method A): [M+H]To a solution of 5-bromo-2-fluoropyridine (10 g, 56.8 mmol) in EtOH (120 ml) was added hydrazine hydrate (14.22 g, 284 mmol), the mixture was heated to reflux and stirred overnight (16 hr). The solvent of the reaction mixture was evaporated about half under reduced pressure, then cooling in an ice bath there precipitation was occurred, filtered and washed the product with a minimum of EtOH and water, dried in vacuum to obtain pure desired product as white powder (10.2 g, yield 91percent). LCMS (method A): [M+H]1) 5-bromo-2-hydrazinopyridine; Hydrazine monohydrate (10 ml) was added to a solution of 2, 5-dibromopyridine (10.0g) in pyridine (100ml) at room temperature, and the mixture was heated under reflux for 13 hours. After cooling with air, the reaction solvent was evaporated under reduced pressure. To the residue were added 0.5N aqueous sodium hydroxide and chloroform and phases were separated. The organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure to give 5-bromo-2-hydrazinopyridine (7.61 g, 96percent) as a solid. To a solution of 2, 5-dibromopyridine (10.50 g, 44 mmol) in 210 mL of pyridine was added hydrazine hydrate (80percent, 8.85 g, 176.4 mmol), and the mixture was heated to 110° C. and stirred further for 2 hours, then cooled to rt, and concentrated in vacuo. The residue was diluted with DCM (1500 mL). The resulted mixture was washed with aqueous NaOH solution (1 M, 350 mL), dried over anhydrous NaA mixture of 2, 5-dibromopyridine (3; 15.4 g, 65.0 mmol), hydrazine hydrate (30 mL), and propan-2-ol (30 mL) was refluxed for 12 h, and the excess hydrazine hydrate was removed under vacuum. The residue was suspended in cold H2O (50 mL), and the precipitate formed was collected by filtration and washed with ice cold H2O (2 × 15 mL). The obtained precipitate was recrystallized from EtOH to give off-white or pale beige crystals; yield: 10.89 g (89percent); mp 134–135 °C (EtOH) (Lit.20 mp 134–136 °C); Rf = 0.6 (CHCl3–EtOAc). IR (KBr): 3294, 3248, 3172, 2925, 2854, 1595, 1504, 1477, 989, 808 cm–1.1H NMR (CDCl3): δ = 3.80 (br s, 2 H, NH2), 5.95 (br s, 1 H, NH), 6.67 (d, J = 8.8 Hz, 1 H, H-3), 7.55 (dd, J1 = 8.8 Hz, J2 = 2.2 Hz, 1 H, H-4), 8.15 (d, J = 2.2 Hz, 1 H, H-6).13C NMR (CDCl3): δ = 107.8, 108.6, 139.5, 147.5, 159.6.MS (EI, 70 eV): m/z (percent) = 189 (96, [M (81Br)]+), 187 (100, [M (79Br)]+), 159 (35), 157 (35), 117 (11), 92 (16), 78 (71), 64 (55), 51 (65), 50 (57).Anal. Calcd for C5H6BrN3: C, 31.94; H, 3.22; N, 22.35. Found: C, 32.06; H, 3.13; N, 22.46.A mixture of 2, 5-dibromopyridine (44.2 [G, ] 0. [187MOLES), ] hydrazine hydrate (55percent by weight, 105.7 mL, 1.87 mol), poly (ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is refluxed gently for 29 hours. The mixture is then cooled and stirred for 20 hours. To the resulting slurry, cold water (220 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3x) and dried in a vacuum-oven (40-45 [°C)] for 48 hours. The title compound (30.5 g, 87percent) is obtained as off- white flakes. A) [5-BROMO-PVRIDINE-2-YL-HVDRAZINE] A mixture of 2, 5-dibromopyridine (44.2 [G, ] 0. [187MOLES), ] hydrazine hydrate (55percent by weight, 105.7 mL, 1.87 mol), poly (ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is refluxed gently for 29 hours. The mixture is then cooled and stirred for 20 hours. To the resulting slurry, cold water (220 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3x) and dried in a vacuum-oven (40-45 [°C)] for 48 hours. The title compound (30.5 g, 87percent) is obtained as off- white flakes. A) [5-BROMO-PVRIDINE-2-VL-HVDRAZINE] A mixture of 2, 5-dibromopyridine (44.2 g, 0. [187MOLES), ] hydrazine hydrate [(55percent] by weight, 105.7 mL, 1.87 mol), poly (ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is refluxed gently for 29 hours. The mixture is cooled and stirred for 20 hours. To the resulting slurry, cold water (220.0 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3x) and dried in a vacuum-oven [(40-45°C)] for 48 hours. The title compound (30.5 g, 87percent) may be obtained as off-white flakes.A) [5-BROMO-PVRIDINE-2-VL-HVDRAZINE] A mixture of 2, 5-dibromopyridine (44.2 g, 0. [187MOLES), ] hydrazine hydrate [(55percent] by weight, 105.7 mL, 1.87 mol), poly (ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is [REFLUXED] gently for 29 hours. The mixture is cooled and stirred for 20 hours. To the resulting slurry, cold water (220.0 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3x) and dried in a vacuum-oven (40-45 [°C)] for 48 hours. The title compound (30.5 g, 87percent) may be obtained as off-white flakes.A) [5-BROMO-PVRIDINE-2-VL-HVDRAZINE] A mixture of 2, 5-dibromopyridine (44.2 g, 0.187 mol), hydrazine hydrate (55percent by weight, 105.7 mL, 1.87 mol), poly (ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen was [REFLUXED GENTLY] for 29 hours. The mixture was cooled and stirred for 20 hours. To the resulting slurry, cold water (220.0 mL) was added. The slurry was stirred for an additional 30 minutes and filtered. The cake was washed with cold water (3x) and dried in a vacuum-oven (40-45 [°C)] for 48 hours. The title compound (30.5 g, 87percent) was obtained as off-white flakes.A mixture of 2, 5-dibromopyridine (44.2 g, 0. [187MOLES), ] hydrazine hydrate [(55percent] by weight, 105.7 mL, 1.87 mol), poly (ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is refluxed gently for 29 hours. The mixture is cooled and stirred for 20 hours. To the resulting slurry, cold water (220.0 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3x) and dried in a vacuum-oven [(40-45°C)] for 48 hours. The title compound (30.5 g, 87percent) may be obtained as off-white flakes.A 12L three-necked round-bottomed flask equipped with a mechanical stirrer and a condenser, connected on top with a nitrogen [BUBBLER] and a thermometer, was charged with 2, 5-dibromopyridine (442 g, 1. [87MOLES), ] hydrazine hydrate (55percent wt., 1057 ml, [18.] 7 moles), poly (ethylene glycol) (average Mn about 300, 1. 87 L), 2-butanol (373 [ML)] and water (1.87 L). The mixture was heated at reflux for 29 hours. The heating source was removed and the mixture was stirred for an additional 20 hours. To the resulting slurry, cold water [(2.] 2L) was added. The slurry was stirred for an additional [30] minutes and filtered. The cake was washed with cold water (3 x [200] [ML)] and dried in a vacuum-oven [(40°C)] for 48 hours. The title compound was obtained as off-white flakes (305 g, yield 87percent). GCMS (m/z): 187 (M+). [HAPOS;NMR] (400 MHz, [CDCI3)] : 8 8.14 (d, J=2.0 Hz, 1H), 7.55 (dd, J=8.7/2. 0 Hz, 1 H), 6.66 (d, J=8.7Hz, [1 H), ] 5.89 (brs, 1 H), 3.65 (brs, 2H).A 12L three-necked round-bottomed flask equipped with a mechanical stirrer and a condenser, connected on top with a nitrogen bubbler and a thermometer, was charged with 2, 5-dibromopyridine (442 g, 1.87 moles), hydrazine hydrate (55percent wt., 1057 ml, 18.7 moles), poly(ethylene glycol) (average Mn about 300, 1.87 L), 2-butanol (373 ml) and water (1.87 L). The mixture was heated at reflux for 29 hours. The heating source was removed and the mixture was stirred for an additional 20 hours. To the resulting slurry, cold water (2.2L) was added. The slurry was stirred for an additional 30 minutes and filtered. The cake was washed with cold water (3.x.200 ml) and dried in a vacuum-oven (40° C.) for 48 hours. The title compound was obtained as off-white flakes (305 g, yield 87percent). [0178] GCMS(m/z): 187 (M+). H1 NMR (400 MHz, CDCl3): δ8.14 (d, J=2.0 Hz, 1H), 7.55 (dd, J=8.7/2.0 Hz, 1H), 6.66 (d, J=8.7 Hz, 1H), 5.89 (brs, 1H), 3.65 (brs, 2H).; A mixture of 2, 5-dibromopyridine (44.2 g, 0.187 moles), hydrazine hydrate (55percent by weight, 105.7 mL, 1.87 mol), poly(ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is refluxed gently for 29 hours. The mixture is cooled and stirred for 20 hours. To the resulting slurry, cold water (220.0 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3.x.) and dried in a vacuum-oven (40-45° C.) for 48 hours. The title compound (30.5 g, 87percent) may be obtained as off-white flakesPreparation 1 5-BROMO-PYRIDIN-2-YL-HYDRAZINE A 12 L three-necked round-bottomed flask equipped with a mechanical stirrer and a condenser, connected on top with a nitrogen bubbler and a thermometer, was charged with 2, 5-dibromopyridine (442 g, 1.87 moles), hydrazine hydrate (55percent wt., 1057 ml, 18.7 moles), poly(ethylene glycol) (average Mn about 300, 1.87 L), 2-butanol (373 ml) and water (1.87 L). The mixture was heated at reflux for 29 hours. The heating source was removed and the mixture was stirred for an additional 20 hours. To the resulting slurry, cold water (2.2 L) was added. The slurry was stirred for an additional 30 minutes and filtered. The cake was washed with cold water (3.x.200 ml) and dried in a vacuum-oven (40° C.) for 48 hours. The title compound was obtained as off-white flakes (305 g, yield 87percent). [0186] GCMS(m/z): 187 (M+). H1 NMR (400 MHz, CDCl3): δ 8.14 (d, J=2.0 Hz, 1H), 7.55 (dd, J=8.7/2.0 Hz, 1H), 6.66 (d, J=8.7 Hz, 1H), 5.89 (brs, 1H), 3.65 (brs, 2H).A) 5-Bromo-pyridine-2-yl-hydrazine [0213] A mixture of 2, 5-dibromopyridine (44.2 g, 0.187 moles), hydrazine hydrate (55percent by weight, 105.7 mL, 1.87 mol), poly(ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is refluxed gently for 29 hours. The mixture is cooled and stirred for 20 hours. To the resulting slurry, cold water (220.0 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3.x.) and dried in a vacuum-oven (40-45° C.) for 48 hours. The title compound (30.5 g, 87percent) may be obtained as off-white flakes.A 12L three-necked round-bottomed flask equipped with a mechanical stirrer and a condenser, connected on top with a nitrogen bubbler and a thermometer, was charged with 2, 5-dibromopyridine (442 g, 1.87 moles), hydrazine hydrate (55percent wt., 1057 ml, 18.7 moles), poly(ethylene glycol) (average Mn about 300, 1.87 L), 2-butanol (373 ml) and water (1.87 L). The mixture was heated at reflux for 29 hours. The heating source was removed and the mixture was stirred for an additional 20 hours. To the resulting slurry, cold water (2.2L) was added. The slurry was stirred for an additional 30 minutes and filtered. The cake was washed with cold water (3.x.200 ml) and dried in a vacuum-oven (40° C.) for 48 hours. The title compound was obtained as off-white flakes (305 g, yield 87percent). [0178] GCMS(m/z): 187 (M+). H1 NMR (400 MHz, CDCl3): δ 8.14 (d, J=2.0 Hz, 1H), 7.55 (dd, J=8.7/2.0 Hz, 1H), 6.66 (d, J=8.7 Hz, 1H), 5.89 (brs, 1H), 3.65 (brs, 2H). A) 5-Bromo-pyridine-2-yl-hydrazine [0204] A mixture of 2, 5-dibromopyridine (44.2 g, 0.187 moles), hydrazine hydrate (55percent by weight, 105.7 mL, 1.87 mol), poly(ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen is refluxed gently for 29 hours. The mixture is then cooled and stirred for 20 hours. To the resulting slurry, cold water (220 mL) is added. The slurry is stirred for an additional 30 minutes and filtered. The cake is washed with cold water (3.x.) and dried in a vacuum-oven (4045° C.) for 48 hours. The title compound (30.5 g, 87percent) is obtained as off-white flakes.A 12 L three-necked round-bottomed flask equipped with a mechanical stirrer and a condenser, connected on top with a nitrogen bubbler and a thermometer, was charged with 2, 5-dibromopyridine (442 g, 1.87 moles), hydrazine hydrate (55percent wt., 1057 ml, 18.7 moles), poly(ethylene glycol) (average Mn about 300, 1.87 L), 2-butanol (373 ml) and water (1.87 L). The mixture was heated at reflux for 29 hours. The heating source was removed and the mixture was stirred for an additional 20 hours. To the resulting slurry, cold water (2.2 L) was added. The slurry was stirred for an additional 30 minutes and filtered. The cake was washed with cold water (3200 ml) and dried in a vacuum-oven (40 C.) for 48 hours. The title compound was obtained as off-white flakes (305 g, yield 87percent). [0085] GCMS(m/z): 187 (M+). H1 NMR (400 MHz, CDCl3): d 8.14 (d, J=2.0 Hz, 1H), 7.55 (dd, J=8.7/2.0 Hz, 1H), 6.66 (d, J=8.7 Hz, 1H), 5.89 (brs, 1 H), 3.65 (brs, 2H).A 12L three-necked round-bottomed flask equipped with a mechanical stirrer and a condenser, connected on top with a nitrogen bubbler and a thermometer, was charged with 2, 5-dibromopyridine (442 g, 1.87 moles), hydrazine hydrate (55percent wt., 1057 ml, 18.7 moles), poly(ethylene glycol) (average M, about 300, 1.87 L), 2-butanol (373 ml) and water (1.87 L). The mixture was heated at reflux for 29 hours. The heating source was removed and the mixture was stirred for an additional 20 hours. To the resulting slurry, cold water (2.2 L) was added. The slurry was stirred for an additional 30 minutes and filtered. The cake was washed with cold water (3.x.200 ml) and dried in a vacuum-oven (40° C.) for 48 hours. The title compound was obtained as off-white flakes (305 g, yield 87percent). [0187] GCMS(m/z): 187 (M+). H1 NMR (400 MHz, CDCl3): δ 8.14 (d, J=2.0 Hz, 1H), 7.55 (dd, J=8.7/2.0 Hz, 1 H), 6.66 (d, J=8.7 Hz, 1H), 5.89 (brs, 1H), 3.65 (brs, 2H).A) 5-Bromo-pyridine-2-yl-hydrazine [0212] A mixture of 2, 5-dibromopyridine (44.2 g, 0.187 mol), hydrazine hydrate (55percent by weight, 105.7 mL, 1.87 mol), poly(ethylene glycol) (187.0 mL), 2-butanol (37.3 mL) and water (187.0 mL) under nitrogen was refluxed gently for 29 hours. The mixture was cooled and stirred for 20 hours. To the resulting slurry, cold water (220.0 mL) was added. The slurry was stirred for an additional 30 minutes and filtered. The cake was washed with cold water (3.x.) and dried in a vacuum-oven (40-45° C.) for 48 hours. The title compound (30.5 g, 87percent) was obtained as off-white flakes.A mixture of 2, 5-Dibromo-pyridine (13 g, 55.1 MMOL) and hydrazine (13 mL, 414 MMOL) in pyridine (13 mL) was heated at 85 °C for 48 hours. The reaction was cooled and concentrated in vacuo. The residue was triturated in 1N NAOH (20 mL) and toluene (20 mL). The solid was filtered, washed with water, and dried to give the above named compound (6.43 g, 62percent).; A mixture of 2, 5-Dibromo-pyridine (13 g, 55.1 MMOL) and hydrazine (13 mL, 414 MMOL) in pyridine (13 mL) was heated at 85 C for 48 hours. The reaction was cooled and concentrated in vacuo. The residue was triturated in 1 N NAOH (20 mL) and toluene (20 mL). The solid was filtered, washed with water, and dried to give the above named compound (6.43 g, 62percent); A mixture of 2, 5-Dibromo-pyridine (13 g, 55.1 MMOL) and hydrazine (13 mL, 414 MMOL) in pyridine (13 mL) was heated at 85 oc for 48 hours. The reaction was cooled and concentrated in vacuo. The residue was triturated in 1 N NAOH (20 mL) and toluene (20 mL). The solid was filtered, washed with water, and dried to give the above named compound (6.43 G, 62percent).To a solution of 2, 5-dibromopyridine (15 g, 64 mmol) was added NHTo a solution of 2, 5-dibromopyridine (10 g, 42 mmol) in 1-butanol (50 mL), hydrazine hydrate (80percent, 13 mL, 211 mmol) is added at room temperature. After 6 hours at 115° C., the mixture is concentrated to around 15 mL. The white solid is formed and collected by filtration, washed by 30 mL cold water. After dried in the air overnight, Compound 2 (8.0 g) is obtained as an off-white solid.

Molecular Weight:188.03
XLogP3:1.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:186.97451
Monoisotopic Mass:186.97451
Topological Polar Surface Area:50.9
Heavy Atom Count:9
Complexity:88.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes