METHYL 5,6-DICHLORONICOTINATE

Preparation of 5, 6-dichloro-nicotinic acid methyl ester (10)[284] 4.45 niL of sulfuric acid was added to 5.0 g of 5, 6-dichloronicotinic acid (26 mmol) dissolved in 50 niL of methanol, and refluxed under heating and stirring for 18 hours. The mixture was cooled to 4Example 7Preparation of 5, 6-dichloro-nicotinic acid methyl ester (10)4.45 mL of sulfuric acid was added to 5.0 g of 5, 6-dichloronicotinic acid (26 mmol) dissolved in 50 mL of methanol, and refluxed under heating and stirring for 18 hours. The mixture was cooled to 4° C., neutralized with a saturated sodium bicarbonate solution, and methanol was concentrated under reduced pressure. The aqueous layer was extracted with ethyl acetate, and the organic layer was separated to be dried over magnesium sulfate, and concentrated under reduced pressure. The residue was separated by column chromatography (eluting solvent: chloroform/methanol=20/1) to obtain 5.2 g of white solid, 5, 6-dichloro-nicotinic acid methyl ester (yield 97percent).5, 6-Dichloro-nicotinic acid methyl esterA solution of 5, 6-dichloro-nicotinic acid (55.0 g, 281 mmol) in SOCIThionyl chloride (27.9 g, 234 mmol) was added dropwise to the solution of 5, 6-dichloropyridine-3-carboxylic acid (18.0 g, 94 mmol) in MeOH (300 mL) at 0 °C. The resulting mixture was heated under reflux for 3 hours, cooled and concentrated under reduced pressure. The residue was purified by silica chromatography (hexane:EtOAc = 5:1 to 3:1) to give the title compound (6.7 g, 34.7percent yield) as a white solid. MS mlz 226.08 [M+HjtA mixture of 5 6-dichloronicotinic acid (5 g) and sulfurous dichloride (3.10 g) in methanol (20 mL) was stirred at 25overnight. Cold water (100 mL) was added and the resulting mixture was neutralized with sat. NaHCOA mixture of 5, 6-dichloronicotinic acid (5 g) and sulfurous dichloride (3.10 g) in methanol (20 mL) was stirred overnight at 25°C. Cold water (100 mL) was added and the resulting mixture was neutralized with sat. NaHCO3 solution. The aqueous layer was extracted with DCM (2x 100 mL) and the combined organic layers were dried over Na2SO4. Aftet filtration, the filtrate was concentrated in vacuo to give the title compound (5 g) as white solid. MS (ESI): C7H5C12NO2requires 205; found 206 [M+H].Description 123Methyl 5, 6-dichioronicotinate (P123) The mixture of 5, 6-dichloronicotinic acid (5 g) and sulfurous dichloride (3.10 g) in methanol (20 mL) was stirred overnight at 25°C. Cold water (100 mL) was added and the resulted mixture wasneutralized with saturated NaHCO3 solution. The aqueous layer was extracted with DCM (2x 100 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under vacuum to afford the title compound (5 g) as white solid. MS (ESI): C7H5C12NO2 requires 205; found 206 [M+H].Take 5, 6-dichloronicotinic acid (5 g) with thionyl chloride(sulfbrous dichloride) (3.10 g)In methanol (20 mL) was stirred at 25 ° C overnight. Add cold water (100 mL) and the resulting mixture was neutralized with saturated NaHCO3 solution. The aqueous layer was extracted with DCM (2 x 100 mL) and the combined organic layers were dehydrated by Na2S04. After filtration, the filtrate was concentrated in vacuo to give the title compound (5 g) as a white solid.5, 6-Dichloro-nicotinic acid methyl esterA solution of 5, 6-dichloro-nicotinic acid (10.0 g, 51.0 mmol) and DMF (7 μl) in SOCITo a 25OmL reaction vessel was added 5, 6-dichloronicotinic acid (15.6mmol), toluene (5OmL), and methanol (50 mL). The reaction mixture was cooled to 0Preparation B: Reaction 1 : Methyl 5, δ-dichloropyridine-S-carboxylateTo a 25OmL reaction vessel was added 5, 6-dichloronicotinic acid (15.6mmol), toluene (5OmL), and methanol (50 mL). The reaction mixture was cooled to 0°C and a 2M solution of trimethylsilyldiazomethane in hexanes (23.4mmol) was subsequently added dropwise followed by stirring for about 1-2-18 hours. Concentration of the reaction mixture to EPO 5, 6-Dichloro-nicotinic Acid Methyl Ester A 250ml_ round bottomed flask was charged with

Molecular Weight:206.02
XLogP3:2.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:204.9697338
Monoisotopic Mass:204.9697338
Topological Polar Surface Area:39.2
Heavy Atom Count:12
Complexity:177
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes