2,6-Dibromo-3-pyridinol

5.40 Step 1. Synthesis of 2, 6-dibromopyridin-3-ol (39): 38 39 To a 10percent aqueous NaOH solution (300ml) was added bromine (48.6 ml, 946 mmol) at O C. An ice cooled solution of pyridin-3-ol (38; 30 g, 315 mmol) in 10ml 10percent NaOH solution was then added slowly. The reaction mixture was stirred for 15 min at 0 C and 45 min at room temperature. The resulting precipitate was filtered and the filtrate was acidified with aqueous HCl (pH = 4) upon which the crude product precipitated out. The resulting precipitate was filtered and purified by chromatography (EtO Ac/petroleum ether = 1 :20) to give the target compound 39(3Og, 43.9percent yield). MS (ESI) calcd for CA solution (cooled to 0 °C) of bromine (8.1 mL, 158 mmol) in 2 N NaOH (160 mL) was added over 30 min to a solution of pyridin-3-ol (34a; 5.0 g, 53 mmol; Sigma-Aldrich, St. Louis, MO) in 2 N NaOH (55 mL) at 0 °C. The resulting mixture was stirred at 0 °C for 30 min, then allowed to stand for 2 h at ambient temperature. The reaction mixture was vacuum filtered, and the filtrate was adjusted to pH ~ 1 by adding conc. HCl to the a stirred filtrate at 0 °C. The resulting precipitate was collected by vacuum filtration, rinsed with water, and dried in vacuo to give an off-white solid (8 g). This material was dissolved in CClStep a: 2, 6-dibromopyridin-3-ol To a 3N aqueous NaOH solution (790 ml) was added bromine (40.7 ml, 0.789 mol) at 0 °C. An ice cooled solution of pyridine-3-ol (25 g, 0.263 mol) in 150 ml 10 percent NaOH solution was then added slowly and the mixture was stirred at ambient temperature for 18 hours, filtered and the filtrate was acidified with cone. HCI to pH 2. The precipitate was filtered off, washed with HPreparation of 7lPrepared according to the method of Wishka et al, WO 2002/100857.Bromine (21.6 mL, 421 mmol) was added dropwise to a stirred solution of sodium hydroxide (39.2 g, 976 mmol)) in water (800 mL) at 0 °C. The resultant bromate solution was then added dropwise to a stirred solution of 3-hydroxypyridine (20.0 g, 210 mmol), and sodium hydroxide (8.4 g, 34.3 mmol) in water (50 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 90 minutes, acidified to pH 2 by addition of 12M HCl soln., and the resultant precipitate collected, washed with water and dried on the filter. The solid was dissolved in EtOAc (170 mL), the solution diluted with heptane (620 mL) and allowed to crystallise for 3 days. The solid was collected, to give 2-bromopyridin-3-ol, and the mother liquor concentrated in vacuo to give a pale yellow solid. The crude solid was recrystallised from EtOH/water and dried in vacuo to afford 71 as a pale yellow crystalline solid (10.8 g, 42.7 mmol, 20percent).EXAMPLE 7 [0594] Preparation of 71 [0595] Prepared according to the method of Wishka et al, WO 2002/100857. [0596] Bromine (21.6 mL, 421 mmol) was added dropwise to a stirred solution of sodium hydroxide (39.2 g, 976 mmol)) in water (800 mL) at 0° C. The resultant bromate solution was then added dropwise to a stirred solution of 3-hydroxypyridine (20.0 g, 210 mmol), and sodium hydroxide (8.4 g, 34.3 mmol) in water (50 mL) at 0° C. The reaction mixture was stirred at 0° C. for 90 minutes, acidified to pH 2 by addition of 12M HCl soln., and the resultant precipitate collected, washed with water and dried on the filter. The solid was dissolved in EtOAc (170 mL), the solution diluted with heptane (620 mL) and allowed to crystallise for 3 days. The solid was collected, to give 2-bromopyridin-3-ol, and the mother liquor concentrated in vacuo to give a pale yellow solid. The crude solid was recrystallised from EtOH/water and dried in vacuo to afford 71 as a pale yellow crystalline solid (10.8 g, 42.7 mmol, 20percent).General procedure: To a solution of Compound 136 (2.62 g, 10.4 mmol) in DMSO (4.5 mL) were added K2CO3 (1.35 g, 9.8 mmol) and methyl iodide (2.2 mL, 35.3 mmol), and the reaction mixture was stirred at 60 C for 1 h. The mixture was cooled to room temperature and poured into water (50 mL) and filtered. The resulting solids were washed with ice cold water and dried under vacuum to give Compound 137 (2.5 g, 90% yield). MS for C6H5Br2NO, found 268 (MH+).

Molecular Weight:252.89
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:252.85609
Monoisotopic Mass:250.85814
Topological Polar Surface Area:33.1
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes