5-Bromo-3-chloro-2-fluoropyridine

2) 5-Bromo-3-chloro-2-fluoropyridine: To a round-bottom flask containing5-bromo-3-chloropyridin-2-amine (9.47 g, 45.6 mmol) was added hydrogen tertrafluoroborate (30 mL, Aldrich) and the mixture was cooled to -78 [00548] Example 106d (28 mg, 0.13 mmol), and Na2C03 (20 mg, 0.20 mmol) were added to the cooled mixture of Example 106c (crude mixture, 0.065 mmol), followed by water (0.3 mL) and Pd(dppf)Cl2 (3 mg). Then the mixture was degassed by bubbling N2 through the solution for 2 min using a syringe needle. After that, the mixture was heated at 95C for 1.5 h. The mixture was concentrated and directly purified by Prep-TLC (DCM/MeOH = 20/1) to give the desired product Example 106 (3.0 mg, yield 10% over two steps) as a white solid. LCMS [M+l]+ = 465.1. 1H NMR (400 MHz, Chloroform-) delta 10.50 (s, 1H), 8.36 (d, J= 1.8 Hz, 1H), 8.24 (s, 1H), 8.20-8.06 (m, 4H), 7.97 (t, J= 7.9 Hz, 1H), 7.73 (dd, J= 7.9, 2.1Hz, 1H), 7.61 (d, J= 7.8 Hz, 1H), 4.78 (s, 2H), 4.69 (s, 2H), 3.98 (d, J= 5.1Hz, 2H), 2.36 (s, 2H).[00528] To a mixture of Example 99a (100 mg, 0.22 mmol), Example 99b (69 mg, 0.33 mmol), and Na2C03 (70 mg, 0.66 mmol) in Dioxane/H20 (2 mL, v/v = 10/1) was added Pd(dppf)Cl2 (10 mg). Then the mixture was degassed by bubbling N2 through the solution for 2 min using a syringe needle. After that, the mixture was heated at 90C for overnight. The mixture was concentrated under reduced pressure and the residue was purified by prep-HPLC to give the desired product Example 99 (15.4 mg, yield 16%) as a white solid. LCMS [M+l]+ = 465.0. 1H NMR (400 MHz, DMSO- 6) delta 1 1.16 (s, 1H), 8.67 (s, 1H), 8.58-8.50 (m, 2H), 8.26 (d, J= 2.4 Hz, 1H), 8.05 (t, J= 7.9 Hz, 1H), 7.98 (dd, J= 8.6, 2.4 Hz, 1H), 7.86 (dd, J= 1 1.6, 7.9 Hz, 2H), 7.39 (d, J= 8.7 Hz, 1H), 4.36 (t, J= 4.5 Hz, 2H), 4.29-4.20 (m, 2H), 2.44 (s, 2H), 1.95 (s, 2H).

Molecular Weight:210.43
XLogP3:2.6
Hydrogen Bond Acceptor Count:2
Exact Mass:208.90432
Monoisotopic Mass:208.90432
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:103
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes