Oxalyl chloride → HCID 22250337, compound

To a solution 0.8 g (4 mmol) of 4-methyl-2-trifluoromethylpyrimidine-5-carboxylic acid [made by the method of Palanki et al, J. Med. Chem. 2000, 43, 3995] stirring in 15 mL of methylene chloride, oxalyl chloride (2 mL, 23 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 (1 g, 5 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 (200 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, which was suspended in a small amount of ethyl acetate and filtered to afford (after drying) 650 mg of the title compound, a compound of the present invention, melting at 248-251° 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 (200 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, which
12. filtrationfiltered
13. customto afford
14. dry with material(after drying) 650 mg of the title compound

ORD record

ord-c5561dcb92744e23becf7dcc63db891b

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06747047B2