3,5-Dichloro-2-fluoropyridine

Pale yellow crystalline powder

To bring a thermometer, Into a four-necked flask with a reflux condenser and a stirrer, 93.1 g of 2, 3, 5-trichloropyridine (98% by mass, 0.50 mol), 300mL sulfolane, 32.2g of powdered potassium fluoride (99% by mass, 0.55mol), Heating to a temperature of 155-160 C and maintaining it for 8h, Sampling and analysis, at this time the content of 2, 3, 5-trichloropyridine is less than 1.0%, stop the reaction, cool to room temperature, filter, and wash the solid three times with sulfolane (10 mL each time).The filtrate and washings were combined.To the To a suspension of 76 1-(2, 5-difluoro-4-(2-(2-isobutoxy-6-methylphenyl)-4, 5, 6, 7-tetrahydro-2H-pyrazolo[4, 3-c]pyridin-3-yl)phenyl)urea (3.0 g, 6.6 mmol) in 78 DMSO (10 mL) was added 79 3, 5-dichloro-5-fluoro pyridine (1.6 g, 9.9 mmol) and 80 Li2CO3 (1.9 g, 25.7 mmol) at room temperature. The resulting mixture was stirred at 90 C. for 4 h. After completion of the reaction, the mixture was cooled to room temperature, and diluted with EtOAc. The organic layer was washed with brine, and dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by silica gel flash chromatography (10 to 60% 38 EtOAc in hexanes) to afford 81 1-(4-(5-(3, 5-dichloropyridin-2-yl)-2-(2-isobutoxy-6-methylphenyl)-4, 5, 6, 7-tetrahydro-2H-pyrazolo[4, 3-c]pyridin-3-yl)-2, 5-difluorophenyl)urea.1H NMR (400 MHz, CD3OD): delta 8.15 (d, J=2.3 Hz, 1H), 8.02 (dd, J=7.1, 12.5 Hz, 1H), 7.84 (d, J=2.3 Hz, 1H), 7.32 (t, J=7.8 Hz, 1H), 6.92 (d, J=8.2 Hz, 1H), 6.89 (d, J=7.5 Hz, 1H), 6.82 (dd, J=6.3, 11.3 Hz, 1H), 4.87 (br, 2H), 4.39 (s, 2H), 3.70- 3.82 (m, 4H), 3.65 (dd, J=7.1, 9.0 Hz, 1H), 3.07 (t, J=6.7 Hz, 2H), 2.02 (s, 3H), 1.85-1.95 (m, 1H), 0.85 (d, J=7.0 Hz, 6H). MS: (ES) m/z calculated C29H29Cl2F2N6O2 [M+H]+ 601.2, found 601.5.

Molecular Weight:165.98
XLogP3:2.6
Hydrogen Bond Acceptor Count:2
Exact Mass:164.9548326
Monoisotopic Mass:164.9548326
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes