Toluene → N-Cyclopropyl-6-iodo-4-(trifluoromethyl)nicotinamide

Cyclopropylamine (862 mg, 15.1 mmol) was dissolved in 4 ml of dichloromethane and admixed dropwise under argon with a solution of trimethylaluminium in toluene (2 M, 7.55 ml, 15.1 mmol). The mixture was stirred for 30 min, and then methyl 6-iodo-4-(trifluoromethyl)nicotinate (500 mg, 1.51 mmol) (synthesis analogous to J. Med. Chem., 2008, 51, 3133-3144 by esterification of nicotinic acid) dissolved in 3 ml of dichloromethane was added dropwise. The mixture was heated under reflux overnight and, after cooling to room temperature, water was added cautiously. The mixture was extracted with ethyl acetate, the organic phase washed with potassium sodium tartrate solution, dried over magnesium sulphate and filtered, and the filtrate concentrated under reduced pressure. The purification was effected by means of silica gel chromatography with the eluent cyclohexane/ethyl acetate (EA) (0% EA to 30% EA).

1. additionwas added dropwise
2. temperatureThe mixture was heated
3. temperatureunder reflux overnight
4. extractionThe mixture was extracted with ethyl acetate
5. washthe organic phase washed with potassium sodium tartrate solution
6. dry with materialdried over magnesium sulphate
7. filtrationfiltered
8. concentrationthe filtrate concentrated under reduced pressure
9. customThe purification

ORD record

ord-87f04127f5eb4530a2941fa176c03cf0

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889878B2