Hydrochloric Acid → HCID 71252239, compound

Ethyl 6-amino-2-methylnicotinate (450 mg) and triethylamine (0.42 mL) were dissolved in methylene chloride (5 mL), 4-chlorobutyryl chloride (0.31 mL) was added, and the mixture was stirred at room temperature for 3 days. To the reaction mixture was added saturated brine, and the mixture was extracted with methylene chloride. The solvent was evaporated, and the obtained residue was purified by column chromatography (ethyl acetate:hexane). The solvent was evaporated, and to the obtained residue were added N,N-dimethylformamide (3 mL) and sodium hydrogen carbonate (420 mg), and the mixture was stirred at 80° C. After completion of the reaction, to the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The solvent was evaporated, ethanol (2 mL) and 1N aqueous sodium hydroxide solution (2 mL) were added to the obtained crude product (300 mg) of ethyl 2-methyl-6-(2-oxopyrrolidin-1-yl)nicotinate, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was neutralized with 1N hydrochloric acid, saturated brine was added, and the mixture was extracted with ethyl acetate. The solvent was evaporated to give a crude product of 2-methyl-6-(2-oxopyrrolidin-1-yl)nicotinic acid. Using the obtained crude product (0.605 mmol) of 2-methyl-6-(2-oxopyrrolidin-1-yl)nicotinic acid and 1-(3,5-dimethylpyridin-2-yl)piperazine (116 mg) described in Preparation Example 79 and by the reaction and treatment in the same manner as in Example 93, the title compound (9 mg) was obtained.

1. extractionthe mixture was extracted with methylene chloride
2. customThe solvent was evaporated
3. customthe obtained residue was purified by column chromatography (ethyl acetate:hexane)
4. customThe solvent was evaporated
5. additionto the obtained residue were added N,N-dimethylformamide (3 mL) and sodium hydrogen carbonate (420 mg)
6. stirringthe mixture was stirred at 80° C
7. customAfter completion of the reaction
8. extractionthe mixture was extracted with ethyl acetate
9. customThe solvent was evaporated
10. additionethanol (2 mL) and 1N aqueous sodium hydroxide solution (2 mL) were added to the
11. customobtained crude product (300 mg) of ethyl 2-methyl-6-(2-oxopyrrolidin-1-yl)nicotinate
12. stirringthe mixture was stirred at room temperature for 2 hr
13. additionwas added
14. extractionthe mixture was extracted with ethyl acetate
15. customThe solvent was evaporated

ORD record

ord-5651562ebe9e4a3392f190654f5a2154

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08816079B2