Oxalyl chloride → 2-[1-Ethyl-3-trifluoromethylpyrazol-5-yl carbamoyl]-3-methyl-N-(1-methylethyl)benzamide

To a solution of 1-ethyl-3-trifluoromethyl-pyrazol-5-yl carboxylic acid (0.5 g, 2.4 mmol) stirring in 20 mL of methylene chloride, oxalyl chloride (1.2 mL, 14 mmol) was added. Upon addition of 2 drops of N,N-dimethylformamide, foaming and bubbling occurred. The reaction mixture was heated at reflux for 1 hr as a yellow solution. After cooling, the solvent was removed in vacuo and the resulting residue dissolved in 20 mL of tetrahydrofuran. To the stirred solution, 2-amino-3-methyl-N-(1-methylethyl)benzamide (0.7 g, 3.6 mmol) was added followed by the dropwise addition of N,N-diisopropylethylamine (3 mL, 17 mmol). After stirring at room temperature overnight, the reaction mixture was partitioned between ethyl acetate (100 mL) and 1N aqueous hydrochloric acid (75 mL). The separated organic layer was washed with water and brine and dried over magnesium sulfate. Evaporating in vacuo gave a white solid residue, which on purification by flash column chromatography on silica gel (2:1 hexanes/ethyl acetate) afforded 0.5 g of the title compound, a compound of the present invention, melting at 223-226° C.

1. custombubbling
2. temperatureThe reaction mixture was heated
3. temperatureat reflux for 1 hr as a yellow solution
4. temperatureAfter cooling
5. customthe solvent was removed in vacuo
6. dissolutionthe resulting residue dissolved in 20 mL of tetrahydrofuran
7. customthe reaction mixture was partitioned between ethyl acetate (100 mL) and 1N aqueous hydrochloric acid (75 mL)
8. washThe separated organic layer was washed with water and brine
9. dry with materialdried over magnesium sulfate
10. customEvaporating in vacuo
11. customgave a white solid residue, which
12. customon purification by flash column chromatography on silica gel (2:1 hexanes/ethyl acetate)

ORD record

ord-56d49cb751c340b684561a26f495b6e0

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07338978B2