6-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine

Step b) Formation of 6-bromo[1 , 2, 4]triazolo[1 , 5-a]pyridin-2-amine A suspension of ethyl {[(5-bromopyridin-2-yl)amino]carbonothioyl}carbamate (12.3 g, 40.4 mmol), hydroxylamine hydrochloride (14.1 g, 202 mmol) and DIEA (15.7 g, 122 mmol) in a mixture of MeOH and EtOH (ratio 1 :1 , 200 ml.) was stirred at RT for 2 hours and then at 70A suspension of ethyl {[(5-bromopyridin-2-yl)amino]carbonothioyl}carbamate (12.3 g, 40.4 mmol), hydroxylamine hydrochloride (14.1 g, 202 mmol) and DIEA (15.7 g, 122 mmol) in a mixture of MeOH and EtOH (ratio 1 :1 , 200 ml_) was stirred at RT for 2 hours and then at 7012.83 g (184.632 mmol) of hydroxylamine hydrochloride and 14.32 g (110.779 mmol) N, N- diisopropylamine were dissolved in 70 ml methanol/ethanol (v/v = 1:1). .sect.0.4 g of the compound from example 105 A was added and the mixture was stirred at room temperature for 2 h and at 60°C for 3 h. After cooling, water and ethyl acetate were added, the organic phase was removed and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, concentrated in a rotary evaporator and the residue was dried under high vacuum. We obtained 7.02 g (96percent of theor.) of the target compound.GC-MS (method 6): R, = 6.11 min; MS (EIpos): m/z = 212 [M]b) 6-Bromo-[ 1 , 2, 4] triazolo[ 1 , 5-a]pyridin-2-ylamineA mixture of hydroxylamine hydrochloride (40.0 g, 575 mmol) and N- ethyldiisopropylamine (44.6 g, 60.3 ml, 345 mmol) in ethanol (734 ml) was stirred for a few minutes at 25 °C, then the mixture was added to l-ethoxycarbonyl-3-(5-bromo-pyridin-2-yl)- thiourea (35 g, 115 mmol) and the resulting mixture was refluxed for 1 day. The solvent was evaporated under reduced pressure and the white solid was treated with 400 ml water. The suspension was stirred for 1 hour, the solid was filtered off, washed with water 3 times and dried under reduced pressure, affording 6-bromo-[l, 2, 4]triazolo[l, 5-a]pyridin-2-ylamine (21 g, 85percent) as white solid. Mp.: 185°C. MS: m/z=213.0/215.1 (M+H+).2.2 6-Bromo-[1, 2, 4]triazolo[1, 5-a]pyridin-2-ylamine (3) To a suspension of hydroxylamine hydrochloride (409.2 g, 5.888 mol) in EtOH/MeOH (1 :1, 2.5 L) was added JV, jV-diisopropylethylamine (606.1 mL, 3.480 mol), the mixture was stirred at room temperature (20 6-Bromo-[1 , 2, 4]triazolo[1 , 5-a]pyridln-2-amine (PZ972-2): DMAP (2.82 g, 23.1 mmol) was added to a mixture of PZ972-1 (2.34 g, 7.7 mmol), hydroxylamine HCl salt (2.67 g, 38.5 mmol) in methanol/ethanol (20 mL 20 mL). The reaction was stirred at rt for 1.5 h, then at 60 °C for 3 h. The solvent was removed under vacuum, and the resulting residue was partitioned between dichloromethane (30 mL) and water (30 mL). The water phase was extracted with dichloromthane (30 mLx2). The organic phases were collected, dried over anhydrous sodium sulfate, and concentrated. The crude product was washed with petroleum ether to get PZ972-2 (1 g, 60.9percent). LC-MS: 213.2, 215.2 (M+l).Hydroxylammoniumchlorid (39.8 g) was suspended in methanol (200 mL) and ethanol (190 mL) and Hiinig Base (59 mL) was added at r.t. The mixture was heated to 60°C, Int01.01 (30 g) was added portionwise, and the mixture was stirred at 60 °C for 2h. The solvent was removed in vacuum and water (150 mL) was added. A solid was collected by filtration and was washed with water and dried in vacuum. Yield: 19.3 g of the title compound. Hydroxylammonium chloride (39.8 g) was suspended in methanol (200 mL) and ethanol (190 mL) and Hiinig Base (59 mL) was added at r.t. The mixture was heated to 60°C, Int01.01 (30 g) was added portionwise, and the mixture was stirred at 60° C for 2h. The solvent was removed in vacuum and water (150 mL) was added. A solid was collected by filtration and was washed with water and dried in vacuum. Yield: 19.3 g of the title compound. Hydroxylammoniumchlorid (39.8 g) was suspended in methanol (200 mL) and ethanol (190 mL) and Hunig Base (59 mL) was added at r.t. The mixture was heated to 60°C, Int01 .01 (30 g) was added portionwise, and the mixture was stirred at 60 °C for 2h. The solvent was removed in vacuum and water (150 mL) was added. A solid was collected by filtration and was washed with water and dried in vacuum. Yield: 19.3 g of the title compound. Hydroxylammonium chloride (39.8 g) was suspended in methanol (200 mL), and ethanol (190 mL) and Hiinig Base (59 mL) were added at r.t. The mixture was heated to 60°C, Int01.01 (30 g) was added portionwise, and the mixture was stirred at 60 °C for 2h. The solvent was removed in vacuum, and water (150 mL) was added. A solid was collected by filtration and was washed with water and dried in vacuum. Yield: 19.3 g of the title compound.1H-NMR (300MHz, DMSO-d6): δ [ppm] = 6.10 (s, 2H), 7.28 (dd, 1 H), 7.51 (dd, 1 H), 8.88 (dd, 1 H).Hydroxylammonium chloride (39.8 g) was suspended in methanol (200 mL) and ethanol (190 mL) and Hünig Base (59 mL) was added at r.t. The mixture was heated to 60°C, IntOl.01 (30 g) was added portionwise, and the mixture was stirred at 60°C for 2h. The solvent was removed in vacuum and water (150 mL)was added. A solid was collected by filtration and was washed with water and dried in vacuum.Yield: 19.3 g of the title compound.1H-NMR (300MHz, DMSO-d6): 6 [ppm] = 6.10 (5, 2H), 7.28 (dd, 1H), 7.51 (dd, 1H), 8.88 (dd, 1H).Hydroxylammonium chloride (39.8 g) was suspended in methanol (200 mL) and ethanol (190 mL) and Hünig Base (59 mL) was added at r.t. Step 2; To a solution of hydroxylamine hydrochloride (345 mg) in ethanol-methanol (1:1) (10 mL), diisopropylethylamine (0.5 mL) was added. The solution was then stirred at room temperature for 1 hour. To the solution, 55 (303 mg, 1 mmol) was added, followed by reflux. After the starting material was consumed, the reaction mixture was cooled. The precipitate was collected by filtration, and then washed sequentially with water, ethanol-methanol (1:1), and diethyl ether to yield target compound 56 (100 mg, y. 51percent).

Molecular Weight:213.03
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:211.96976
Monoisotopic Mass:211.96976
Topological Polar Surface Area:56.2
Heavy Atom Count:11
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes