2-Amino-5-bromopyridine

Light yellow Cryst

General procedure: Nitrobenzene (0.6mmol), 5wtpercent Pd/C (0.5mmol percent, 0.003mmol), H2O (10 equiv, 6.0mmol), B2(OH)4 (3.3 equiv, 2.0mmol), and CH3CN (1.0mL) were added in a 10mL tube. The reaction mixture was stirred at 50°C for 24h. When the reaction was complete monitored by TLC, the mixture was cooled to room temperature. Water (5mL) was added, and extracted with EtOAc (3×5mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give aniline 2a (55mg, 99percent).To the mixture of pyridin-2-ylamine (10.0 g, 106 mmol) in acetone (200 mL), was added NBS (22.6 g, 127 mmol) portionwise at 0°C. The mixture was warmed to room temperature and stirred overnight. Solvent was evaporated in vacuum. The residue was purified by silica gel column (DCM/MeOH, 20/1) to afford 18 g (yield: 98percent) of 5-bromo-pyridin-2- ylamine as yellow solid. [00589] 1H NMR (DMSO-d6): δ = 7.94 (IH, d), 7.61 (IH, dd), 6.43 (IH, d), 6.10 (2H, brs).4.5.4 14.8 g (89.4 mmol) of potassium bromate was dissolved in the succinimide aqueous solution recovered in the previous step.In the condition of 25 °C, stirring, 17.5 mL of 50percent sulfuric acid aqueous solution was added dropwise. After the addition, the reaction was completed for 2.5 h. The reaction was completed, filtered and dried to obtain 42 g of N-bromosuccinimide.After dissolving 41.8 g of 2-aminopyridine in 175 mL of acetone, the solution was cooled to -5 to -3 °C, and a solution of bromine in acetone (35.4 g of bromine/160 mL of acetone) was added dropwise with stirring.The reaction temperature was controlled at -5 ~ 0 °C, and the reaction was completed for 0.5 h after the addition was completed until the raw materials reacted completely.The temperature of the solution was adjusted to -1 to 1 °C, and 42 g of self-made reconstituted N-bromosuccinimide was added in batches. The reaction temperature was 2 to 4 °C. The reaction was continued for 1 h after the addition was complete.After the reaction, the mixture was recovered with acetone, separated by adding an aqueous potassium hydroxide solution, and recrystallized to obtain 69.9 g of brown crystals of 2-amino-5-bromopyridine in a yield of 91percent and a purity of 99.0percent.[00159] Scheme 1. Preparation of relevant pyri(mi)dyl halides A-H. Key: (a) NBS, NHGeneral procedure: To a mixture of 2-aminopyridine (0.5 mmol, 1 equiv), p-TSA (0.4 mmol, 0.8 equiv), 1-butylpyridinium bromide (1.5 mmol, 3 equiv) in a 50 mL Schlenk tube were added 1, 2-dimethoxyethane (2 mL) under air. Then H52.3 g (0.555 mol) of 2-aminopyridine and 500 mL of acetonitrile were added to a 1-necked 1 L flask.And 103.9 g (0.584 mol) of NBS (N-bromosuccinimide) was added thereto at a temperature of 5 ° C for 4 times. The temperature was gradually raised to room temperature and the mixture was stirred for 24 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, 1000 mL of water and 1000 mL of DCM were added, and the mixture was stirred for 2 hours. The separated organic layer was washed with 500 mL of brine, dried over anhydrous Na2SO4, and concentrated. The concentrate was recrystallized under DCM / Hexane conditions to obtain 81.5 g (yield: 84.8percent) of a compound as a white solid (Intermediate (14)).A 1L flask was charged with 52.3 g (0.555 mol) of 2-aminopyridine, and acetonitrile (500 mL) were added. At the temperature of 5 °C., 103.9 g (0.584 mol) of NBS (N-bromosuccinimide) And the temperature was gradually raised to room temperature and stirred for 24 hours. After confirming the completion of the reaction, the reaction solution was concentrated under reduced pressure, 1000 mL of water and 1000 mL of dichloromethane (DCM) were added, and the mixture was stirred for 2 hours. The separated organic layer was washed with 500 mL of brine, dried over anhydrous Na2SO4, and concentrated. The concentrate was recrystallized under dichloromethane (DCM) / hexane to obtain 81.5 g (yield: 84.8percent) of a white solid compound (Intermediate 40).General procedure: To a - 20°C solution of 2-aminopyridineor 2-amino-4-chloropyridine(1 equiv) in DMF was added N-bromosuccinimide(1.1 or 2.2 equiv.) in two portions. The reaction mixture was stirred for 16 hat room temperature and was then poured withstirring into a 1M solution of NaOH (50 mL). The phases were separated and theaqueous layer was extracted with EtOAc. The combined organic phases were washedwith water (2 x 50 mL) and brine (50 mL), dried over MgSOTo a solution of pyridin-2-amine (10.0 g, 10.06 mmol) in acetonitrile (100 mL) at -30°C NBS (18.9 g, 106.2 mmol) was added and the resulting solution was stirred at -30°C for 30 mm. The reaction mixture was quenched with ice and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous Na2SO4. The organic layer was concentrated under vacuo. The product was purified by column chromatography to yield title compound (10.0 g, 54.37percent) as a yellow solid. LCMS: (M+2) = 175.0To a solution of pyridin-2-amine (10.0 g, 10.06 mmcl) in acetonitrile (100 mL) at 3000 NBS (18.9 g, 106.2 mmol) was added and it was stirred at 300C for 30 mm.The reaction mixture was quenched with ice and extracted with ethyl acetate. Theorganic layer was washed with water and dried over anhydrous Na2SO4. The organiclayer was concentrated under vacuo. The product was purified by column chromatography to yield title compound (10.0 g, 54.37percent) as a yellow solid. LCMS:(M+2) = 175.0To a solution of 2-aminopyridine (9.40 g, 0.1 mol) in EtOH (100 mL) was added dropwise Br2 (5.8 mL, 0.11 mol) maintaining the temperature below 20 °C. When the addition of bromine was completed, the mixture was stirred for 1 h. After removal of EtOH, the residue was made alkaline with a solution of NaOH (5.0 g, 0.13 mol) in H2O (50 mL) and cooled (10 °C). The solid was collected by filtration, slurry washed with cold H2O (10 mL), and then washed with boiling heptane (3 × 20 mL) to remove the 2-amino-3, 5-dibromoaminopyridine, followed by air-drying to constant weight; yield: 13.15 g (76percent); off-white fine crystals; mp 135–136 °C (Lit.17 mp 132–135 °C); Rf = 0.4 (CHCl3–EtOAc). IR (KBr): 3452, 3292, 3153, 2924, 2852, 1628, 1587, 1550, 1481, 1387, 1088, 999 cm–1.1H NMR (CDCl3): δ = 4.57 (br s, 2 H, NH2), 6.41 (d, J = 8.8 Hz, 1 H, H-3), 7.48 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1 H, H-4), 8.09 (d, J = 2.4 Hz, 1 H, H-6).13C NMR (CDCl3): δ = 108.3, 110.1, 140.2, 148.7, 157.1.MS (EI, 70 eV): m/z (percent) = 174 (88, [M (81Br)]+), 172 (100, [M (79Br)]+), 147 (46), 145 (49), 92 (97), 65 (67), 64 (60), 50 (49).Anal. Calcd for C5H5BrN2: C, 34.71; H, 2.91; N, 16.19. Found: C, 34.59;H, 3.01; N, 16.10.28.2 g (0.3 moles) of 2-aminopyridine were dissolved in 50 ml of acetic acid. The solution is cooled to below 20° by immersion in an ice bath, and 48 g (15.4 ml, 0.3 moles) of bromine dissolved in 30 ml of acetic acid is added dropwise with vigorous stirring over a period of 1 h. Initially the temperature is maintained below 20°. After half the bromine solution has been added, it is allowed to rise to 50° to delay as long as possible the separation of the hydrobromide of 2-amino-5-bromopyridine. At 50° the hydrobromide usually begins to crystallize when about three-quarters of the bromine has been added. When addition of bromine is completed, the mixture is stirred for 1 h and is then diluted with 75 ml of water to dissolve the hydrobromide. The contents of the flask are transferred to a 500 ml beaker and are neutralized, with stirring and cooling, by the addition of 120 ml of 40percent sodium hydroxide solution. 2-Amino-5-bromopyridine, contaminated with some 2-amino-3, 5-dibromopyridine, was filtered and dried. The 2-amino-3, 5-dibromopyridine is removed from the product by washing with three 500-ml. portions of hot petroleum ether. The yield of 2-amino-5-bromopyridine, is 32-34.7 g (62-67percent). mp 134 °C (literatureGeneral procedure: To a solutionof diazo-compound (1 mmol, 1 eq.) in n-hexane(10 mL) was added TMSI (1.3 eq.) dropwise at 0°C. After addition of TMSI, the suspension was stirred for 8h at rt. The suspension was then filtered and, the residue was dried and used as such for next step without purification.To a solutionof silyl-protected diazo-compound (1 eq.) in EtOH (1 ml) was added SnCl

2-Amino-5-bromopyridine is an organic synthesis intermediate and pharmaceutical intermediate. It can be used in the laboratory research and development process and the chemical medicine research and development process. It can be used as a raw material for the preparation of drugs and fine chemicals.

Molecular Weight:173.01
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:171.96361
Monoisotopic Mass:171.96361
Topological Polar Surface Area:38.9
Heavy Atom Count:8
Complexity:76.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes