2-Chloropyridine-5-sulfonylchloride

A solution of 10 g (79.2 mmol) of 3-amino-6-chloropyridine in concentrated HCl (16 mL) and glacial acetic acid (89 mL) was cooled to 10° C. in an ice batch. 5.46 g (79.2 mmol) of sodium nitrite were added portionwise keeping the temperature below 15° C. The mixture was stirred for 1 h, then added dropwise to a solution of sulfur dioxide (car 27 mL), 2.77 g (16.2 mmol) of copper (II) chloride dihydrate and acetic acid (59 mL) in water (11 mL) over 10 min at 5° C. The reaction mixture was allowed to warm to room temperature and poured over ice/water (300 mL) and stirred for a further 15 min. The resultant precipitate was isolated by filtration, washed with water (2.x.100 mL) and dried under reduced pressure to afford 12.99 g of 6-chloro-pyridine-3-sulfonyl chloride; 6-chloropyridine-3-sulfonyl chloride. At -10 In a 250mL three neck round bottom flask equipped with an overhead stirrer was charged 27mL water, and cooled to -3° C (ice/NaCl). Thionyl chloride (4.52mL, 61.96mmol, 4.5eq) was added slowly so the temperature did not exceed 7° C. The ice bath was removed, allowed to warm to room temperature, then 0.07g (0.69mmol, 0.05 eq) of copper (I) chloride was added. The mixture was then recooled to -5° 5-Amino-2-chloropyridine (1.77g, 13.67mmol) was dissolved in 14 mL of concentrated HCl and cooled to -5° C to which a solution of 1.04g (15.14 mmol, 1.1eq) NaNO2 in 12mL of water was added slowly so the temperature was maintained between -5 and 0°C. This mixture was then added to the thionyl chloride/water/CuCl mixture. A frothing precipitate resulted and was allowed to stir for another 30 min. The product was filtered and air dried. Solids were taken up in ethyl acetate, washed with brine, dried over MgSO4 and concentrated in vacuo to afford 1.7g (62percent) of 6-chloro-pyridine-3-sulfonyl chloride as a light tan solid. Electrospray Mass Spec 210.9 (M+H)+Sodium nitrite (3.45g, 0.05mol) was added portion wise to a stirred solution of 6- chloro-pyridin-3-ylamine (6.4g, 0.05mol) in acetic acid (56ml) and HCl (cone)(9.92ml) while maintaining the temperature below 15°C. This solution was then added drop wise to a stirred solution of sulfur dioxide (17.2g, 0.27mol), copper (II) chloride (1.85g, 0.01 lmol) and water (2.2ml) in acetic acid (37ml) at 5°C. The reaction mixture was allowed to warm to room temperature and poured over ice water and stirred for a further 15min. The resultant precipitate was collected by filtration, washed with water and dried overnight in a vacuum oven to give 6- chloro-pyridine-3-sulfonyl chloride (6.41g, 60.5percent yield); (400 MHz; d6-Chloro-pyridine-3-sulfonyl chloride; Sodium nitrite (3.45g, 0.05mol) was added portion wise to a stirred solution of 6- chloro-pyridin-3-ylamine (6.4g, 0.05mol) in acetic acid (56ml) and HCl (cone) (9.92ml) while maintaining the temperature below 15°C. This solution was then added drop wise to a stirred solution of sulfur dioxide (17.2g, 0.27mol), copper (II) chloride (1.85g, 0.01 lmol) and water (2.2ml) in acetic acid (37ml) at 5°C. The reaction mixture was allowed to warm to room temperature and poured over ice water and stirred for a further 15min. The resultant precipitate was collected by filtration, washed with water and dried overnight in a vacuum oven to give 6- chloro-pyridine-3-sulfonyl chloride (6.41g, 60.5percent yield); (400 MHz; dReference Example 31 6-chloropyridin-3-ylsulfonyl chloride; Under ice-cooling, thionyl chloride (12 mL) was added dropwise over 1 hr to water (70 mL) and the mixture was stirred at room temperature for 12 hr to give a sulfur dioxide-containing solution. Separately, under ice-cooling, 5-amino-2-chloropyridine (5.0 g) was added to concentrated hydrochloric acid (40 mL) and the mixture was stirred. An aqueous solution (12.5 mL) of sodium nitrite (2.88 g) was added dropwise while keeping the inside temperature at not higher than 5° C., and the mixture was further stirred for 15 min. The reaction mixture was gradually added at 5° C. to the above-mentioned sulfur dioxide-containing solution added with cuprous chloride (70 mg). Under ice-cooling, the mixture was further stirred for 30 min. The precipitate was collected by filtration, and washed with water and ethanol to give the title compound (yield 4.79 g, 58percent). Reference Example 134 Thionyl chloride (60 mL, 823 mmol) was added to water (360 mL) at 0° C. over 60 min so that the temperature was maintained between 0 and 7° C. Example 131

Molecular Weight:212.05
XLogP3:1.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:210.9261549
Monoisotopic Mass:210.9261549
Topological Polar Surface Area:55.4
Heavy Atom Count:11
Complexity:223
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes