5-BROMO-PYRIDINE-2-SULFONYL CHLORIDE

(b) 5-Bromopyridine-2-sulfonyl chloride; 2-Benzylsulfanyl-5-bromo-pyridine (3.0 g, 10.71 mmol) was dissolved in CHPhenylmethanethiol (80.0 g, 645 mmol) was dissolved in anhydrous tetrahydrofuran (600 ml), and 60percent sodium hydride (45.0 g, 1.13 mol) was added thereto, followed by stirring at room temperature for 30 minutes. To this reaction solution, 5-bromo-2-chloropyridine (123 g, 640 mmol) was added, followed by stirring at room temperature for 3 hours. The reaction solution was diluted with water, followed by extraction with diethyl ether. The extraction liquids were combined, washed with a saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. Then, the solvent was removed. A compound (250 g, 0.90 mol) obtained by repeating the-above described process was suspended in a mixture solvent of acetic acid (2250 ml) and water (750 ml), and N-chlorosuccinimide (340 g, 2.60 mol) was added thereto, followed by stirring at room temperature for 2 hours. The reaction solution was diluted with water, followed by extraction with methylene chloride. The extraction liquids were combined, washed with a saturated aqueous sodium hydrogen carbonate solution and water, and dried over anhydrous sodium sulfate. Then, the solvent was removed. The obtained residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=30:1). The obtained compound (47.0 g, 185 mmol) and methyl 4-amino-2, 6-difluorobenzoate (26.0 g, 139 mmol) were suspended in methylene chloride (1000 ml), and pyridine (30 ml) was added thereto, followed by stirring at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=4:1) to obtain the title compound (50 g, 15percent over three steps).(Step 5) 5-Bromopyridine-2-sulfonyl chloride (0334) (0335) 2-Benzylsulfanyl-5-bromo-pyridine (250 g, 0.89 mol) was suspended in acetic acid (2, 250 ml) and water (750 ml), NCS (340 g, 2.60 mol) was added thereto, and the resulting mixture was stirred at room temperature for 2 hours. The reaction liquid was diluted with water and extracted with methylene chloride. The extracts were combined, washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated saline solution, and dried over magnesium sulfate. The obtained residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=30:1) to obtain the title compound (60.4 g, 26percent).Step B Preparation of mt 2-2 To a solution of mt 2-1 (1.5 g, 5.40 mmol) in DCM (100 mL) was added water (100 mL) and HCOOH (100 mL). The heterogeneous mixture was cooled to 0°C and Cl2 gas was bubbled for 30 minutes until the mixture turned to deep yellow. The organic phase wasseparated, extracted with DCM (3 x 100 mL) and the combined organic phase was washed with1M NaOH (100 mL) followed by brine (100 mL), concentration to provide a residue (1.1 g) of mt 2-2 which was used for the next step without purification.To a solution oflnt 2-1 (1.5 g, 5.40 mmol) in DCM (100 mL) was added water(100 mL) and HCOOH (100 mL). The heterogeneous mixture was cooled to 0°C and Ch gaswas bubbled for 30 minutes until the mixture turned to deep yellow. The organic phase was5 separated, extracted with DCM (3 x 100 mL) and the combined organic phase was washed with1M NaOH (100 mL) followed by brine (100 mL), concentration to provide a residue (1.1 g) ofInt 2-2 which was used for the next step without purification.A mixture of crude 2-(benzylthio)-5-bromopyridine (prepared in Compound 2, 7.74 g, 27.6mmol, Eq: 1.00), water (80.0 ml), and carbon tetrachloride (300 ml) was cooled to 0 °C in an ice bath and vigorously stirred while chlorine gas was bubbled slowly through the mixture. After 3 minutes the reaction mixture was saturated with chlorine and turned bright yellow green. Bubbling was continued for 10 minutes followed by 5 additional minutes of stirring under a chlorine blanket before the mixture was sparged of chlorine by bubbling argon into the solution for 10 minutes. The mixture was diluted with dichloromethane (100 ml) and the phases separated. The organic phase was washed with water (100 ml), a saturated sodium bicarbonate solution (100 ml) and brine and then dried over magnesium sulfate. The mixture was filteredand evaporated to give 5-bromopyridine-2-sulfonyl chloride as a semi-crystalline solid (4.34 g, 61percent).A suspension of 5-bromo-pyridine-2-thiol (which may be prepared as described for Intermediate 1.05; 2 g, 10.5 mmol) in carbon tetrachloride (40 mL) and water (8 mL) was cooled to 0° C. using an ice-bath. Chlorine gas was bubbled through the reaction mixture for 20 min and then CH

Molecular Weight:256.51
XLogP3:1.9
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:254.87564
Monoisotopic Mass:254.87564
Topological Polar Surface Area:55.4
Heavy Atom Count:11
Complexity:225
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes