6-Chloro-4-methyl-3-pyridinesulfonyl chloride

A mixture of 6-chioro-4-methyipyridine-3-sulfonyl chloride (0.25 g, 1.106 mmol) in THF (5 mL) was treated with Hunig's Base (0.290 mL, 1.659 mmol), followed by dimethylamine (2.0 M in THF, 0.829 mL, 1.659 mmol) at room temperature. After 1 hour, the reaction was concentrated and the crude was purified by column chromatography (24g Si02, 0 to 100% EtO Ax-hexanes, gradient elution) to afford 6- chloro-N, N, 4-trimethylpyridine-3-sulfonamide (213 mg, 0.908 mmol, 82 % yield). LCMS(M+H) = 234.9; LCMS RT = 0.79 min; (Column: BEH Cl 8 2.1 x 50mm; Mobile Phase A: water with 0.05% TFA; Mobile Phase B: acetonitrile with 0.05% TFA; Temperature: 50 C; Gradient: 2-98% B over 1.7 min; Flow: 0.8 mL/min).2-Chloro-4-methyl-5-nitropyridine (lg, 5.8 mmol) was dissolved in EtOH (60 mL). AcOH (4 mL) and Fe (5 eq. ) were added and the mixture was refluxed at 80C overnight. The mixture was filtered through celite and reduced under vacuum to afford the crude 5-amino-2-chloro-4-methylpyridine which was used in the next step with no further purification. The amine was dissolved in cone. HC1 (6 mL), transferred to a 3-neck round bottom flask, and cooled to-5 C. A solution of NaNO2/H2O (440 mgs/5 mL) was slowly added and the mixture was allowed to stir for 10 mins. To a second, separate 3-neck round bottom flask was added H20 (12 mL) and cooled to-5 C. Thionyl chloride (4.5 eq. ) was then added dropwise. After complete addition the mixture was allowed to warm to room temp. Whereupon CuCl (. 05 eq. ) was added and the mixture was then cooled back down to -5C. The first reaction mixture, containing the amine precursor, was slowly added to the second reaction mixture. A froth formed and was filtered off to afford 2-Chloro-4-methyl-5-nitropyridine (lg, 5.8 mmol) was dissolved in EtOH (60 mL). AcOH (4 mL) and Fe (5 eq. ) were added and the mixture was refluxed at 80C overnight. The mixture was filtered through celite and reduced under vacuum to afford the crude 5-amino-2-chloro-4-methylpyridine which was used in the next step with no further purification. The amine was dissolved in cone. HC1 (6 mL), transferred to a 3-neck round bottom flask, and cooled to-5 C. A solution of NaNO2/H2O (440 mgs/5 mL) was slowly added and the mixture was allowed to stir for 10 mins. To a second, separate 3-neck round bottom flask was added H20 (12 mL) and cooled to-5 C. Thionyl chloride (4.5 eq. ) was then added dropwise. After complete addition the mixture was allowed to warm to room temp. Whereupon CuCl (. 05 eq. ) was added and the mixture was then cooled back down to -5C. The first reaction mixture, containing the amine precursor, was slowly added to the second reaction mixture. A froth formed and was filtered off to afford

Molecular Weight:226.08
XLogP3:2.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:224.9418050
Monoisotopic Mass:224.9418050
Topological Polar Surface Area:55.4
Heavy Atom Count:12
Complexity:249
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes