2,5,6-Trifluoronicotinic aicid nitrile

2, 6-Dichloro-5-fluoro-nicotinonitrile (25.67 g, 134 mmol) and spray-dried KF (23.6 g, 406 mmol) (Aldrich), both of which had been freshly powdered under air to remove clumps, were shaken together to ensure complete mixing before adding dry DMSO (30 mL). The mixture was efficiently stirred at rt under argon for 1-2 min, and then placed in a 100° C. oil bath and stirred for 5 min. The temperature was then raised to 130° C. over the course of 10 min, and the mixture was stirred at this temperature for 40 min. The NMR spectrum of reaction aliquots demonstrated 86percent conversion after 10 min at 130° C., and >95percent conversion after 40 min. The thick purple mixture was then allowed to cool to rt, shaken with DCM (30 mL) on an ice bath, and then loaded directly onto a flash silica column (1.0 kg silica gel; 120 mm.x.6) pre-equilibrated with DCM. DCM elution (140 mL fractions; fractions 10-19 combined) afforded 20.65 g of a clear light amber oil. A NMR spectrum demonstrated a 1:0.58 mol ratio of title compound:DMSO (16.0 g title compound; 76percent). To a solution of 2.5 g (16.0 mmol) of 4-methyl-3-(trifluoromethyl)-1 H-1 , 2, 4-triazol-5-one (CAS 51856-10-1 ) in 40 ml. dimethyl sulfoxide was added 2.4 g (16.0 mmol) of 2, 5, 6-trifluoropyridine- 3-carbonitrile (CAS 870065-73-9) and 2.2 g (16.0 mmol) of potassium carbonate. The mixture was stirred for 16 hours at 20C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgS04, fil- tered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 3.1 g (9.6 mmol, 60%) of the desired compound 2 step 1.1 H-NMR (CDCIs, ppm): 7.96 - 8.08 (m, 1 H); 3.43 - 3.60 (m, 3 H).

A pyridine derivative used in the preparation of JAK2 kinase inhibtors.

Molecular Weight:158.08
XLogP3:1.5
Hydrogen Bond Acceptor Count:5
Exact Mass:158.00918253
Monoisotopic Mass:158.00918253
Topological Polar Surface Area:36.7
Heavy Atom Count:11
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes