Diisopropylethylamine → N-(3,5-Bis-trifluoromethyl-benzyl)-6-chloro-4-(2-chloro-phenyl)-N-methyl-nicotinamide

To a solution of 300 mg (1.12 mmol) 6-chloro-4-(2-chloro-phenyl)-nicotinic acid (Example 24, step e)) in 12 ml dichloromethane 0.15 ml (1.7 mmol) oxalyl chloride and one drop of N,N-dimethylformamide were added at 0° C. After completed addition the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was concentrated in vactio. The residue was redissolved in 6 ml dichloromethane and added dropwise to a solution of 432 mg (1.68 mmol) (3,5-bis-trifluoromethyl-benzyl)-methyl-amine, 0.39 ml (2.2 mmol) N-ethyldiisopropylamine and 7 mg (0.06 mmol) 4-(N,N-dimethylamino)pyridine in 6 ml dichloromethane at 0° C. After completed addition the reaction mixture was allowed to warm to room temperature and stirred over night. The reaction mixture was diluted with dichloromethane and washed with two portions of 1 M aqueous hydrochloric acid solution. The combined aqueous layers were extracted with dichloromethane. The combined organic extracts were washed with two portions of 1 M aqueous sodium hydroxide solution. The combined basic aqueous layers were extracted with dichloromethane. The combined organic extracts were dried with sodium sulfate and concentrated. Column chromatography afforded 475 mg (84%) of the title compound as a light yellow amorphous mass.

1. additionaddition the reaction mixture
2. concentrationThe reaction mixture was concentrated in vactio
3. dissolutionThe residue was redissolved in 6 ml dichloromethane
4. additionaddition the reaction mixture
5. temperatureto warm to room temperature
6. stirringstirred over night
7. washwashed with two portions of 1 M aqueous hydrochloric acid solution
8. extractionThe combined aqueous layers were extracted with dichloromethane
9. washThe combined organic extracts were washed with two portions of 1 M aqueous sodium hydroxide solution
10. extractionThe combined basic aqueous layers were extracted with dichloromethane
11. dry with materialThe combined organic extracts were dried with sodium sulfate
12. concentrationconcentrated

ORDレコード

ord-b6d3dda420d847e29203f0592b33feec

出典データセット

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06770637B2