* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With potassium fluoride; In 1-methyl-pyrrolidin-2-one; at 95.0℃; for 18.0h;
EXAMPLE 225-cyano-6-(isobufylamino)picolinic acid (70) A mixture of <strong>[53234-56-3]6-chloro-5-cyanopicolinic acid</strong> (30 mg, 0.16 mmol), isopropylamine (20 ul, 0.23 mmol), and KF (28 mg, 0.48 mmol) in N-methylpyrrolidinone (1 ml) was heated for 18 hrs at 95 C. The mixture was diluted with water (4ml) and standed overnight. The resulting precipitate was collected by filtration and dried under vacuum to afford 25 mg (75%) of the desired product 70. 1H NMR (600MHz, DMSOd6) delta 13.2 (s, IH), 8.03 (d, IH, J= 7.8 Hz), 7.25-7.21 (m, IH), 7.17 (d, IH, J= 7.8 Hz), 3.26-3.24 (m, 2H), 1.99-1.95 (m, IH), 0.89 (d, 6H, 6.6 Hz). MS: m/z Calcd 219.2 Found MH+ 220.1
Step 2Synthesis of 6-(4-chlorobenzylthio)-5-cyanopicolinic acid (52)A mixture of <strong>[53234-56-3]6-chloro-5-cyanopicolinic acid</strong> (30 mg, 0.16 mmol), 4-chlorophenyl methanethiol (24 ul, 0.18 mmol), and CsCO3 (156 mg, 0.48 mmol) in dimethylformamide (2 ml) was heated for 16 hrs at 45 0 C. After removal of the solvent, the residue was treated with water (2 ml) and acidified with IN-HCl to pH2. The precipitate was collected by filtration and dried under vacuum to afford 40 mg (82%) of the desired product 52. 1H NMR (600MHz, DMSO-d^) delta 13.6 (br s, IH), 8.46 (d, IH, J=7.8 Hz), 8.15 (d, IH, J=7.8 Hz), 7.55 (d, 2H, J=9 Hz), 7.47 (d, 2H, J= 9Hz). MS: m/z Calcd 304.8 Found MH+ 305.0
EXAMPLE 216-(4-chlorobenzylthio)-5-cyanopicolinic acid (52) <n="101"/> Step 1Synthesis of 6-chloro-5-cyanopicolinic acid (51) To a solution of 6-chloro-5-cyano-2-picoline 50 (3.0 g, 20 mmol) in COnC-H2SO4 (20 ml) was added CrO3 (4.9 g, 49 mmol) portionwise over 2 hr period while the reaction mixture was kept below 2O 0 C. After stirring overnight at room temperature, the mixture was poured into ice-water and the resulting solid was collected by filtration to give the crude 6-chloro-5-(aminocarbonyl)-2-picolinic acid which was dissolved in POCl3 (15 ml). After heating at reflux for 30 min, the reaction mixture was concentrated in vacuo and the residue was treated with ice water. The precipitate was collected by filtration to afford 2.5 g (71% for 2 steps) of the desired product 51. 1H NMR (600MHz, DMSO-d6) delta 8.65 (delta, IH, theta= 7.8 Hzeta), 8.17 (delta, IH, theta= 7.8 Hzeta)
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20.0℃; for 4.0h;
Example 18: Preparation of 6-Chloro-5-cyano-pyridine-2-carboxylic acid (2-methyl-5- pentafluoroethyl-4-trifluoromethyl-2H-pyrazol-3-yl)-amideTo a suspension of <strong>[53234-56-3]6-chloro-5-cyano-pyridine-2-carboxylic acid</strong> (5.6 g, 25.2 mmol)(commercially available) in dichloromethane (100 ml) was added N,N-dimethylformamide (0.2 ml) at ambient temperature, followed by oxalyl chloride (3.2 ml, 38 mmol). The reaction mixture was stirred for 4 hour at room temperature and then concentrated. The residue was was used for the next step.2-Methyl-5-pentafluoroethyl-4-trifluoromethyl-2H-pyrazol-3-ylamine (Example II, 6.66 g, 23.5 mmol) was dissolved in tetrahydrofuran (120 ml) and pyridine (2.7 ml, 34 mmol) was added. 6-Chloro-5-cyano-pyridine-2-carboxylic acid chloride was added portionwise. The reaction mixture was stirred at ambient temperature for 19 hours. Then aqueous sodium hydrogen carbonate (saturated) was added and the aqueous phase was extracted three times with ethyl acetate. The combined organic extracts were dried over sodium sulphate, filtered and concentrated. The residue was purified by columnchromatography on silica gel (eluent: heptane / ethyl acetate 3 : 1) to give 6-chloro-5-cyano- pyridine-2-carboxylic acid (2-methyl-5-pentafluoroethyl-4-trifluoromethyl-2H-pyrazol-3-yl)- amide (7.1 g, 71% yield). 1H- MR (400 MHz, CDC13): 9.4 (sb, 1H), 8.35 (d, 1H), 8.31 (d, 1H), 3.90 (s, 3H) ppm.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
