(2-AMINO-PYRIDIN-4-YL)-METHANOL

Light yellow Cryst

26 g of lithiumaluminum hydride was dissolved in 800 mL ofanhydrous THF. A solution of 103 g of methyl ether of2-aminoisonicotinate in 600 mL of anhydrous THFwas added at stirring and the formed slurry was boiledfor 3 h. After cooling water was carefully added, theprecipitate was filtered off and washed with 300 mL ofTHF. The combined filtrates were evaporated, theresidue was crystallized from benzene. Yield 61 g(73percent), mp 80–81.5°. 1H NMR spectrum (DMSO-d6), δ, ppm: 4.36 s (2), 5.19 s (1), 5.78 s (2), 6.40 d(1), 6.46 s (1), 7.81 d (1). 13 NMR spectrum(DMSO-d6), δ, ppm: 62.3, 105.2, 110.3, 147.7, 152.7, 160.3. Found, percent: 57.63; 6.32; N 22.68. C6H8N2O.Calculated, percent: C 58.05; H 6.4; N 22.56.600ml of anhydrous tetrahydrofuran solution of lithium aluminum hydride (115g, 3mol) was added to 200ml of anhydrous tetrahydrofuran solution of methyl aminoisonicotinate (153g, 1mol) for 1 hour at 0°C by dropping. To a stirred, ice-cooled solution of compound 66 (3.68 g, 16.4 mmol), prepared as described in US 6, 720, 328, in CH(2) The obtained compound 2 and NaOH solution were mixed, placed in a reactor, the control temperature is 10 ° C, was added dropwise NaBrO solution, after the completion of the dropwise addition, the reaction continued at this temperature for 1 h, After the temperature was raised to 60° C., the reaction was continued for 1 h, and then the temperature was lowered to room temperature. Multiple extractions were performed using ethyl acetate. The organic phases were combined and the ethyl acetate was distilled off under reduced pressure to obtain the 2-aminopyridine-4-methanol.To a stirred solution of 31 (4.0 g, 20.3 mmol) in CH2Cl2 (60 mL) was added NBS (3.62 g, 20.3 mmol) portionwise at room temperature and the reaction stirred for 30 min. It was then quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was washed with water (100 mL) dried over Na2SO4 and concentrated in vacuo. The obtained crude was purified by column chromatography (6% ethyl acetate in petroleum ether) to afford the intermediate bromoketone (4.0 g, 72%) as a brown oil.1H NMR (400 MHz, CDCl3) delta ppm 8.69 (d, J = 5.2 Hz, 1H), 7.58 (d, J = 5.2 Hz, 1H), 5.54 (s, 1H), 2.31 - 2.25 (m, 1H), 1.26 - 1.13 (m, 4H).LC-MS (MeCN, pH 3): [M+H]+ = 275, 277, 279, rt = 1.68 mins, purity = 84%.To a stirred solution of the bromoketone (4.0 g, 14.5 mmol) in EtOH (100 mL) were added (2-aminopyridin-4-yl) methanol (1.8 g, 14.5 mmol) and molecular sieves (4A, 8.0 g) at room temperature, and the reaction then stirred at 100 C for 16 h. The precipitate was then filtered and washed with CH2Cl2 (100 mL), and the filtrate concentrated in vacuo. Trituration with ethanol then gave the product 32 (2.0 g, 46%) as a pale yellow solid.1H NMR (400 MHz, DMSO-d6) delta ppm 9.41 (d, J = 7.2 Hz, 1H), 8.71 (d, J = 5.2 Hz, 1H), 7.96 (d, J = 5.6 Hz, 1H), 7.51 (s, 1H), 7.10 (dd, J = 7.2, 1.6 Hz, 1H), 5.50 (t, J = 5.6 Hz, 1H), 4.59 (d, J = 5.6 Hz, 2H), 2.38 - 2.35 (m, 1H), 1.11 - 1.09 (m, 4H).LC-MS (MeCN, pH 3): [M+H]+ = 301, 303, rt = 1.16 mins, purity = 78%.

Molecular Weight:124.14
XLogP3:-0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:124.063662883
Monoisotopic Mass:124.063662883
Topological Polar Surface Area:59.1
Heavy Atom Count:9
Complexity:87.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes