3,4-Dichloro-5-isothiazolecarboxylic acid

After three 500 ml round bottom flask was added after the 42.4 g of crude 3, 4-dichloro-isothiazole carbonitrile I was diluted with100 ml of methanol and 30 g of 45percent sodium hydroxide solution, stirred for 2 hours at 40 degrees Celsius, gussets after thedetection of 3, 4-dichloro-isothiazole carbonitrile disappear, concentrated under reduced pressure to remove residual methanol, concentrated hydrochloric acid was added to adjust pH = 3, filtration and washing with water 17.6 g of a white solid of 3, 4-dichloro-isothiazole carboxylic acid II, used directly in the next reaction without purification, the amount of 3, 4-dichloroisothiazolecarboxylic acid II prepared according to the corresponding scaled up or down the volume of the reaction vesselaccording to the corresponding scaled up or down, I have the same commercially available compound effect.Such prior art compounds are for instance:...3-amino-1, 2, 4-triazole, 1-(2-pyridyl)-3-(1, 2, 3-thiadiazole-5-yl)-urea2-butylthio-benzthiazole, 2-(2-methylpropylthio)-benzthiazole, 0.75 mmol of Add 5 mmol of compound I-1 to a 250 ml two-neck round bottom flask. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) is 6 mmol, 1-hydroxybenzotriazole (HOBT) was 5.13 mmol, dissolved in dichloromethane solution and stirred in an ice bath for 15 minutes. A solution of the amine in dichloromethane (25 ml) was added to the reaction system. Then 6 mmol of Et3N was added and the reaction mixture was stirred at room temperature for 16 hours. After the reaction is completed, wash with water (2 × 60 ml) and saturated with brine (80 ml)Wash the organic layer, The organic layer was dried over MgSO4 and concentrated under reduced vacuo. The residue is purified by 100-200 mesh silica gel column chromatography to give compound II-1. The eluent is petroleum ether: ethyl acetate at 60-90 degrees Celsius.Its volume ratio is 4:1, yield 70%; white solid, melting point 125-126%, 3, 4-Dichloroisothiazol-5-ylcarboxylic acid (400 mg, 2.02 mmol) was dissolved in abs. dichloromethane (20 ml), and triethylamine (0.85 ml, 6.06 mmol) was added. After stirring at room temperature for 5 minutes, pyrrolidine-i-amine (209 mg, 2.42 mmol) and 2, 4, 6-tripropyl-1, 3, 5, 2, 4, 6-trioxatriphosphorinane 2, 4, 6-trioxide (1.80 ml, 3.03 mmol, 50percent solution in tetrahydrofuran) were added. The resulting reaction mixture was stirred at room temperature for a further 30 minutes, and then water, sat. sodium hydrogencarbonate solution and dichloromethane were added. The aqueous phase was repeatedly extracted vigorously with dichloromethane, and the combined organic phases were then dried over magnesium sulfate, filtered and concentrated. Final purification of the resulting crude product by colunm chromatography gave 3, 4-dichloro-N-(pyr- rolidin-i-yl)-i, 2-thiazole-5-carboxamide in the form of a colorless solid (520 mg, 92percent of theory). 'H-NMR (400 MHz, CDC13 oe, ppm) 3.38-3.28 (m, 2H), 2.73-2.64 (m, 2H), 2.03-1.98 (m, 4H). 3, 4-Dichloro-N-(pyrrolidin- 1 -yl)-i , 2- thiazole-5-carboxamide (120 mg, 0.45 mmol) was dissolved in abs. tetrahydroffiran (5 ml) under argon, and sodium hydride (40 mg, 1.99 mmol, 60percent purity) was added at room temperature. Stirring at room temperature for 30 minutes was followed by the addition of picolyl chloride (HC1 salt, 74 mg, 0.45 mmol), and the resulting reaction mixture was stirred under reflux conditions for approx. 3 hours. After cooling to room temperature, sat. sodium hydrogencarbonate solution, water and dichloromethane were added. The aqueous phase was repeatedly extracted vigorously with dichloromethane, and the combined organic phases were then dried over magnesium sulfate, filtered and concentrated. Final purification of the resulting crude product by colunm chromatography gave 3, 4-dichloro-N-(pyridin-2-yl- methyl)-N-(pyrrolidin- 1 -yl)-i , 2-thiazole-5-carboxamide in the form of a colorless solid (112 mg, 69percent of theory). 'H-NMR (400 MHz, CDC13 oe, ppm) 8.62 (m, 1H), 7.71-7.67 (m, 1H), 7.53 (m, 1H), 7.33 (m, 1H), 5.15 (s, 2H), 4.18-4.13 (m, 2H), 3.71-3.66 (m, 2H), 2.30-2.24 (m, 2H), 2.13-2.08 (m, 2H).In a 250 ml round bottom flask in water are sequentially added methanol 80 ml, 3, 4-dichloro-thiazole-5-carboxylic acid (10.7 g, 53.8 mmol), gradually under the condition ice bath adds by drops two chlorine Asia sulphone (9.6 g, 80.7 mmol), the drop finishes heated to 40 degree c stirring 5 hours, after the reaction is complete to concentrate, add ethyl acetate to dissolve the filter, the filtrate of the distilled water are used to, saturated NaHCO3saturated NaCl wash again, anhydrous magnesium sulphate dried, concentrated, vacuum drying the white solid obtained 11.2 g, yield 98percent2.1. Synthesis of ethyl 3, 4-dichloroisothiazole-5-carboxylate: 15 g of 15 g of

Molecular Weight:198.03
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:196.9105048
Monoisotopic Mass:196.9105048
Topological Polar Surface Area:78.4
Heavy Atom Count:10
Complexity:156
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes