6-Bromo-1,2,4-triazin-3-amine

3-Amino-1, 2, 4-triazine (I) (0.96 g, 0.01 mol) was added to 100 mL of N, N-dimethylformamide, stirred well, and slowly dropped into 100 mL under ice bath. 0.1 mol of NBS was stirred while stirring, and the reaction was kept at 0-30 ° C for 12 hours. After the reaction was sufficiently completed, 0.3 mol of NaOH was added to the reaction, and then the reaction product was collected by filtration, and dried to obtain the product 3- Amino-6-bromo-1, 2, 4-triazine 1.43 g, yield 81.7percent.1 , 2, 4-Triazine-3-amine (2 g, 20.814 mmol) was dissolved in acetonitrile (20.8 ml) and water (31.5 ml). After the reaction temperature was cooled to 0° C., N-bromosuccinimide (3.89 g, 20.855 mmol) was added thereto. The resulting mixture was agitated for 10 minutes, and then heated to room temperature and agitated.After the reaction termination, the resulting mixture was diluted with ethyl acetate and cooled to 00 C. Sodium carbonate was added thereto, agitated for 10 minutes, and washed with saturated sodium bicarbonate and brine. After drying with anhydrous magnesium sulfate and filtration, the solvent was concentrated under reduced pressure to obtain 6-bromo-1, 2, 4-triazine-3-amine (amount: 2.4 g, yield: 67percent).Water (120 mL) was added to a mixture of 3-amino-1 , 2, 4-triazine (104 mmol, 1 .0 equiv) in acetonitrile (120 mL) and stirred at room temperature until a brown solution was formed. The mixture was cooled to 0 C, treated with N-bromosuccinimide (109 mmol, 1 .05 equiv) in a portionwise manner and stirred at 0 C for 20 min. After warming to room temperature, the mixture was diluted with ethyl acetate (350 mL) and cooled to 0 C. Sodium carbonate (12 g) was added to the mixture and stirred for 10 min. The two layers were separated and the aqueous phase was extracted with ethyl acetate (200 mL). The combined organic layers were washed with aqueous sodium bicarbonate, dried over sodium sulfate, filtered and concentrated to give the 6-bromo-1 , 2, 4-triazin-3- amine (10.5 g, 58percent) as a yellow solid. Step 1: 6-Bromo-1, 2, 4-triazin-3-amine To a suspension of 1, 2, 4-triazin-3-amine (3.84 g, 40.0 mmol) (Aldrich, Cat. No.100625) in acetonitrile (40 mL) was added water (60 mL) and stirred until a clear solution was formed. To this solution was added N-bromosuccinimide (7.48 g, 42.0 mmol) at 0° C. and the resulting mixture was stirred for 10 min. The cooling bath was removed, and the mixture was allowed to warm to room temperature. The mixture was then diluted with ethyl acetate (150 mL) and cooled to 0° C. (ice-water bath). Na1, 2, 4-triazin-3-amine 18a (5.0 g, 52.03 mmol, as disclosed in the patent application 'US2009291956'The method is prepared by dissolving in a mixed solution of 130 mL of acetonitrile and water (V/V=2/3) at 0 ° C.JoinN-iodosuccinimide (9.72 g, 54.63 mmol) was stirred for 0.5 hour. Stop the reaction, The reaction solution was adjusted to pH greater than 7 with a saturated solution of sodium bicarbonate and extracted with ethyl acetate (100 mL×3).The combined organic layers were concentrated under reduced pressure.The title compound 18b (5.2 g, yield: 57.1percent).Example 14: Preparation of 4-hydroxy-3-(4-isopropylbenzoyl)-l-(6-methyl-l, 2, 4- triazin-3-yl)-2-[4-(trifluoromethoxy) henylJ-2H-pyrrol-5-onea) 6-bromo- 1 , 2, 4-triazin-3 -amine (1-24); A mixture of 3-amino-l, 2, 4-triazine (10.0 g, 96 mmol, 1 eq) in water (1300 ml) was cooled to 0-5°C. The bromine (13.3 ml, 159.8 mmol, 2.5 eq) was added dropwise to the reaction mixture for 1 h. Then the mixture was stirred overnight at room temperature. A saturated aqueous NaExample 81 (.pound.)-2-(1 -(7-(quinolin-6-ylmethyl)imidazo[1 , 2-b][1 , 2, 4]triazin-2- yl)ethylidene)hydrazinecarboxamide 81 1 81 26-Bromo-1 , 2, 4-triazin-3-amine (81.1) A mixture of 3-amino-1 , 2, 4-triazine (50.0 g, 521 mmol) in water (6000 ml.) was cooled to 0-5 Intermediate 14 To a suspension of 1, 2, 4-triazin-3-amine (1.30 g, 13.53 mmol) in acetonitrile (13 mE) was added water (20 mE) andmixture was stirred until a clear solution was obtained.The solution was then cooled at 0° C. (ice bath) andN-bromosuccinimide (2.53 g, 14.21 mmol) was added andresulting mixture was stirred for 10 mm. The ice bath was then removed and the mixture was stirred at roomtemperature for 30 mm. Ethyl acetate (50 mE) was then added to the mixture and it was again cooled at 0° C. (ice bath). To this mixture was added solid Na2CO3 (1 g) and stirring was continued for 10 mm before the organic layerwas separated and the aqueous phase was re-extracted with ethyl acetate (2x20 mE). The combined organic extracts were washed (saturated aqueous NaHCO3 solution, 2x20 mE; brine, 20 mE), dried (MgSO4) and evaporated. Theresidue was adsorbed on silica gel using ethyl acetate and was purified on an ISCO column (24 g; DCMJethyl acetate) and fractions containing the desired compound were combined and evaporated to give title product as a white solid(0.924 g, 5.28 mmol, 39.0percent). ECMS (APCI) calcd for C3H4BrN4 [M+H] mlz 174.9, 176.9; found 175.0, 177.0.NMR (400 MHz, DMSO-d5) ö 8.40 (s, 1H), 7.47 (br s, 2H).To a stuffed solution of 1, 2, 4-triazin-3-amine (2.0 g, 20.8 mmol) in methanol:water (2:1; 20 mL) was added a solution of bromine (3.29 g, 20.8 mmol) in methanol. The reaction mixture was stirred at room temperature for 2 h. The solvent was evaporated in vacuo, then the residue was quenched with saturated aqueous NaHCO3 solution and extracted with DCM (3 x 50 mL). The combined organic layers were dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The crude residuewas washed with diethyl ether, to give the title compound (1.4 g, 38percent) as a yellow solid. oH (400 MHz, DMSO-d6) 8.39 (s, 1H), 7.46 (br s, 2H). LCMS (ES+) 174.9 (M+H), RT 1.30 minutes.1, 2, 4-triazine-3-amine (5.00g) in acetonitrile (45mL), Distilled water was dissolved in (75 mL), the dark, under ice-cooling N- bromosuccinimide (10.0 g) was added, the dark, was stirred at room temperature overnight.Distilled water (100mL) was added to the reaction mixture, and the mixture was extracted three times with ethyl acetate (150mL).It was combined and the resulting organic layer, and then dried over anhydrous sodium sulfate was washed with saturated brine.By concentrated to dryness Insoluble materials were filtered off to give the title compound 2.64g (29percent yield).Bromine (3.8 g, 24 mmol) in chloroform (20 mL) was added to a suspension of 1, 2, 4-triazin-3-amine (1.92 g, 20.0 mmol) in chloroform (100 mL). The reaction mixture was stirred at RT for 60 h. The mixture was washed with saturated NaHCOExample 23 A solution of 1, 2, 4-triazin-3-amine (Intermediate 4, purchased from ALDRICH) (3.0 g, 31.2 mmol) in water (200+100 mL) was cooled to 0-5 °C. Bromine (4 mL, 78 mmol) wasadded drop-wise over 45 mm, then the reaction mixture was stirred overnight at room temperature. When all starting material had been consumed according to TLC (5opercent EtAcO:EtOH (3:1)/cyclohexane), a saturated aqueous Na2SO3 solution (100 mL) was added to the reaction mixture and then the mixture was basified to pH 12 by addition of 2 N aqueous NaOH solution. The mixture was extracted with ethyl acetate (2 x 200 mL). The combinedorganic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 6-bromo-1, 2, 4-triazin-3-amine (pale yellow solid, 2.51 g).

Molecular Weight:174.99
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:173.95411
Monoisotopic Mass:173.95411
Topological Polar Surface Area:64.7
Heavy Atom Count:8
Complexity:77.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes