2-ACETYLAMINO-5-BROMOPYRIDINE

White powder

To a 1 L four-necked flask equipped with a magnetic stirrer and thermometer, 46.04 g (0.267 mol) of 2-amino-5-Bromopyridine, was added 500mL dichloromethane at room temperature with stirring to dissolve slowly added dropwise 53.80g (0.527mol) acetic anhydride, Should be 2 to 5 hours, TLC control to the end of the reaction, vacuum distillation, the residue was dissolved in ethyl acetate, 200mL saturated sodium bicarbonateWashed twice and evaporated to dryness to give 56.41 g of 2-acetylamino-5-bromopyridine in a yield of 99.04percent.Step 63a: N-(5-bromopyridin-2-yl)acetamide (Compound 0601-112)To a solution of 2-amino-5-bromopyridine (0.50 g, 2.9 mmol) in THF (10 mL) was added pyridine (343 mg, 4.3 mmol) and acetic anhydride (295 mg, 2.9 mmol) at room temperature and stirred overnight. To the mixture water (30 mL) was added, extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with saturated aqueous NaHC0Step 63a: N-(5-bromopyridin-2-yl)acetamide (Compound 0601-112)[0481]To a solution of 2-amino-5-bromopyridine (0.50 g, 2.9 mmol) in THF (10 mL) was added pyridine (343 mg, 4.3 mmol) and acetic anhydride (295 mg, 2.9 mmol) at room temperature and stirred overnight. To the mixture water (30 mL) was added, extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with saturated aqueous NaHCOSolution of pyridine (343mg, 4.3mmol) in THF (10mL) solution of 2-amino-5-bromopyridine (0.50g, 2.9mmol) and acetic anhydride (295mg, 2.9mmol) was stirred overnight then added at room temperature . With the addition of water (30mL) to the mixture, and the mixture was extracted with ethyl acetate (3x30mL). The combined organic layers were washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, to afford the title compound as a white solid (0.58g, 92percent).Synthesis of N-(5-bromopyridin-2-yl) acetamide [0293] A solution of 5-bromopyridin-2-amine (5.0 g, 28.90 mmol) in acetic anhydride (30 mL) was stirred at 80 °C for 5 h. After the consumption of the starting materials (monitored by TLC), the reaction was diluted with water (50 mL). The obtained solid was filtered and washed with hexane and dried in vacuo to afford N-(5-bromopyridin-2-yl) acetamide (5.0 g, 81percent) as a white solid. 1H-NMR (DMSO-4OAc in water: ACN; 0.50 ml/min); TLC: 50percent EtOAc:hexane (R/. 0.3).To a stirred solution of 5-Bromo-pyridin-2-ylamine (100 mg, 0.578 mmol) in dry THF was added acetic anhydride (70.25 mg, 0.693 mmol). A 2000 mL single-neck round bottom flask was charged with 2-amino-5-bromopyridine (86.50 g, 500 mmol)Acetic anhydride (153 g, 1500 mmol) and 850 ml of acetic acid, Start magnetic stirrer, The mixture in the reaction flask was stirred at 100 ° C for 9 hours.The TLC and GC tests confirmed that the starting 2-amino-5-bromopyridine was completely reacted, Water was added to the reaction solution, The reaction was then suction filtered, the filter cake was washed with ethyl acetate:N-hexane = 1: 4 to give the pure product 2-acetylamino-5-bromopyridine, The filtrate was extracted with ethyl acetate, the extract was removed by rotary evaporation, The crude product was obtained and recrystallized from ethyl acetate: n-hexane = 1: 4 to give the pure product2-acetamido-5-bromopyridine, After drying, the yield was calculated to be 75.40percent with a purity of 99.68percent (HPLC).The 5-bromo-2-aminopyridine(5.8 mmol) and acetyl chloride (7.6 mmol) dissolved in 10 ml ofacetone, stirring 48 hours. After concentrating by get the crude product bycolumn chromatography (dichloromethane/methanol =250/1) title compoundseparated to obtain 480 mg (39percent). General procedure: Phosphoric acid (0.7 mL, 12 mmol) was added to acetonitrile (0.5 mL, 9.5 mmol), the resulting mixture was cooled to 10-15 °C. Then, a mixture of aminopyridine 1a-g (2 mmol) and sodium nitrite (0.56 g, 8 mmol) pretriturated in a mortar was added in small portions at such a rate that allowed us to avoid vigorous liberation of nitrogen oxides. The resulting paste was thoroughly triturated and allowed to stand at 10-15 °C for 10 min and then at 20 °C for the period of time indicated in Table 1. The reaction progress was monitored by TLC (eluent hexane-acetone, 1 : 3) and GCMS. Upon completion, the reaction mixture was diluted with water, neutralized with NaHCO

Molecular Weight:215.05
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:213.97418
Monoisotopic Mass:213.97418
Topological Polar Surface Area:42
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes