2-AMINO-5-BROMO-4 6-DIMETHYLPYRIDINE&

White Powder

preparation of 2-N, N-dimethylamino-5-hydroxy-4-methyl-6-(10- x decyl)-pyridine; 2-Amino-5-bromo-4, 6-dimethylpyridine (13):To a stirred solution containing 2.00g (16.32 mmol) of 2-amino-4, 6-dimethylpyridine in 25 mL of acetonitrile were added 2.90g (16.32 mmol) of N-bromosuccinimide. The reaction mixture was stirred at room temperature under argon atmosphere for 5 h. The formed precipitate was filtered and dried to afford the expected product as a white solid: yield 2.76g (84percent). 1H-NMR(CDC1To a stirred solution containing 2.00 g (16.3 mmol) of 2-amino-4, 6-dimethylpyridine in 25 mL of acetonitrile was added 2.90 g (16.3 mmol) of N-bromosuccinimide. The reaction mixture was stirred at room temperature for 5 h. The formed precipitate was filtered and dried to afford 6-amino-3-bromo-2, 4-dimethylpyridine (8) as a colorless solid: yield 2.76 g (84percent); mp 143–145 °C; silica gel TLC RA mixture of 4, 6-dimethylpyridin-2-amine (3 g) and Bromine (1 .39 mL) taken up in Acetonitrile (30 mL) was stirred at ambient temperature for I h. The mixture was diluted with Water (100 mL) and the precipitate was collected by filteration and dried to afford the title product as a off white solid (3.8 g, 77percent). LCMS: Rt: 1.2 min; MS: mz = 203 (M+1) 1H NMR (300 MHz, Chloroform-d) 67.28 (5, IH), 6.37 (5, 2H), 2.43-2.12 (m, 6H).General 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 HA solution of 2-amino-4, 6-dimethylpyridine (1.22 g, 10 mmol) in 10 mL of glacial acetic acid under NA solution of 2-amino-4, 6-dimethylpyridine (1.22 g, 10 mmol) in 10 mL of glacial acetic acid under NStep 1 The mixture of 4, 6-dimethylpyridin-2-amine (1 g, 8.2 mmol, 1.0 eq) and NBS (1.46 g, 8.2 mmol, 1.0 eq) in CH3CN (30 mL) was stirred at rt overnight. Then the mixture was concentrated, and the residue was purified on silica gel column (PE/EtOAc = 5/1) to afford 5-bromo-4, 6-dimethylpyridin-2-amine as a yellow solid (800 mg, 48percent).Step 1: 5-bromo-4, 6-dimethyl-1, 2-dihydropyridin-2-oneInto a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of H3PO2 (25 mL, 50%, 8.00 equiv) in water (55 mL) with stirring at 0 C., to which was added preparation of 2-N, N-dimethylamino-5-hydroxy-4-methyl-6-(10- x decyl)-pyridine; 2-Amino-5-bromo-4, 6-dimethylpyridine (13):To a stirred solution containing 2.00g (16.32 mmol) of 2-amino-4, 6-dimethylpyridine in 25 mL of acetonitrile were added 2.90g (16.32 mmol) of N-bromosuccinimide. The reaction mixture was stirred at room temperature under argon atmosphere for 5 h. The formed precipitate was filtered and dried to afford the expected product as a white solid: yield 2.76g (84%). 1H-NMR(CDC13) delta 6.22 (s, 1H), 4.39 (br, 2H), 2.48 (s, 3H), 2.25 (s, 3H);13C-NMR (CDC13) 5156.34, 155.23, 148.64, 112.26, 108.10, 25.10, 23.30.To a stirred solution containing 2.00 g (16.3 mmol) of 2-amino-4, 6-dimethylpyridine in 25 mL of acetonitrile was added 2.90 g (16.3 mmol) of N-bromosuccinimide. The reaction mixture was stirred at room temperature for 5 h. The formed precipitate was filtered and dried to afford to a 100 mL 3 -necked round-bottom flask was placed 4, 6-dimethylpyridin-2-amine (1.0 equiv, 19.6 mmol, 2.4 g) and DCM (20 mL). The reaction system was cooled down to -50 C in a liquid nitrogen bath, and l, 3-dibromo-5, 5-dimethylimidazolidine-2, 4-dione (1.0 equiv, 19.6 mmol, 5.6 g) was added. The resulting solution was stirred at -50 C for 30 min and gradually warmed to 25 C in 30 min. The reaction mixture was quenched with saturated NaHCO, (20 mL) and extracted withdichloromethane (2 x 20 mL). The organic layers were combined and concentrated under vacuum to afford 3.2 g (81.0%) of A mixture of 4, 6-dimethylpyridin-2-amine (3 g) and Bromine (1 .39 mL) taken up in Acetonitrile (30 mL) was stirred at ambient temperature for I h. The mixture was diluted with Water (100 mL) and the precipitate was collected by filteration and dried to afford the title product as a off white solid (3.8 g, 77%). LCMS: Rt: 1.2 min; MS: mz = 203 (M+1) 1H NMR (300 MHz, Chloroform-d) 67.28 (5, IH), 6.37 (5, 2H), 2.43-2.12 (m, 6H).General 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 H2O2 (1.2 mmol, 2.4 equiv) was added. The mixture was stirred at 80C for 24 h. And then the mixture was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the products.A solution of 2-amino-4, 6-dimethylpyridine (1.22 g, 10 mmol) in 10 mL of glacial acetic acid under N2 was treated with a solution of 1.6 g (10 mmol) Br2 in 2 mL of glacial acetic acid over 15 minutes with water bath cooling keeping the temperature below 20C. The solution became a solid mass and was allowed to stand at r.t. for 1h. After cooling in an ice bath, the material was made alkaline with 20% cold NaOH solution. Then the mixture was extracted with CH2Cl2 three times, the combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified on silica gel (Hexane-EtOAc, 2:1~1:1) to afford the product (1.37 g, 68%) as a yellow solid.A solution of 2-amino-4, 6-dimethylpyridine (1.22 g, 10 mmol) in 10 mL of glacial acetic acid under N2 was treated with a solution of 1.6 g (10 mmol) Br2 in 2 mL of glacial acetic acid over 15 min with water bath cooling to keep the reaction temperature below 20 C. The solution became a solid mass and was allowed to stand at room temperature for 1 h. After cooling in an ice bath, the material was made alkaline with 20% cold NaOH solution. Then the mixture was extracted with CH2Cl2 three times, the combined organic layer was dried over anhydrous Na2SO4, then filtered and concentrated. The residue was purified on silica gel (Hexane-EtOAc, 2:1 to 1:1) to afford the product (1.37 g, 68%) as a yellow solid. Mp 143-144 C. (lit. [40] 143 C). 1H NMR (CDCl3) 6.24 (s, 1H), 4.32 (br, 2H), 2.50 (s, 3H), 2.28 (s, 3H).Step 1 Preparation of The mixture of 4, 6-dimethylpyridin-2-amine (1 g, 8.2 mmol, 1.0 eq) and NBS (1.46 g, 8.2 mmol, 1.0 eq) in CH3CN (30 mL) was stirred at rt overnight. Then the mixture was concentrated, and the residue was purified on silica gel column (PE/EtOAc = 5/1) to afford

Molecular Weight:201.06
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:199.99491
Monoisotopic Mass:199.99491
Topological Polar Surface Area:38.9
Heavy Atom Count:10
Complexity:118
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes