2,4-dichloro-3-fluoropyridine

Step 1: A mixture of lithium diisopropylamide (2 M in heptane/THF/ ethylbenzene, stabilised with 0.5percent [W/W] LiBr; 3.8 ml, 7.6 mmol) and THF (3 ml) was cooled to-78°C and a solution of 2-chloro-3-fluoropyridine (1.0 [G, 7.] 6 mmol) in THF (2 ml) was added dropwise over 1 min. After [2] h, a solution of hexachloroethane (2.0 g, 8.4 mmol) in THF (3 ml) was added dropwise and stirring continued for 2 h before quenching with saturated aqueous [NH4C1] solution (20 ml) and extraction of the reaction product with EtOAc (100 ml). The organic phase was dried over anhydrous [MGS04] and concentrated im vacuo. The crude material was purified by column chromatography (silica ; 15percent [ET20/ISOHEXANE)] to afford 2, 4-dichloro-3- fluoropyridine (795 mg, 63percent): [5H] (400 MHz, [CDC13)] 7.34 [(1H, ] t, [J 5.] 1), 8.13 [(1H, ] d, [J 5.] 1); [M/Z] (ES+) 166 (100percent, [MH] +). 2, [4-DICHLORO-3-FLUOROPYRIDINE] (495 mg, 3.0 mmol) was converted to 7-chloro-8-fluoroimidazo [[L, ] 2-a] pyridine (225 mg, 44percent) as described in : [8H] (400 MHz, [CD13)] 6.80 [(1H, ] dd, [J 5.] 9, 7. 0), 7.63 [(1H, ] dd, J 1.2, 2.7), 7.66 (1H, s), 7.91 (1H, dd, J 1.2, 7.0); m/z (ES+) 171 (100percent, [MH+). 7-Chloro-8-fluoroimidazo[1, 2-a]pyridine (115 mg, 0.67 mmol) was brominated as described in Example [1, ] affording 3-bromo-7-chloro-8- [FLUOROIMIDAZO] [[L, ] 2-a] pyridine (162 mg, 96percent): [SN] (400 MHz, [CDC13)] 6.95 [(1H, ] dd, [J 5.] 9, 7. 0), 7.64 [(1H, ] s), 7.91 [(1H, ] dd, [J 0.] 8, 7. 0); m/z (ES+) 249 (75percent, [[MH] +), ] 251 (100), 253 (25). [3-BROMO-7-CHLORO-8-FLUOROIMIDAZO] [1, 2-a] pyridine (45 mg, 0.18 mmol) was coupled with 4-fluoro-3- (pyridin-3-yl) phenylboronic acid (49 mg, 0.19 mmol), as described in Example 1, to afford the title compound as a white amorphous solid (49 mg, [80percent)] : [8H] (400 MHz, DMSO) 7.10 [(1H, ] t, J 7.0), 7.54-7. 61 (2H, m), 7.77-7. 81 [(1H, ] m), 7.92 [(1H, ] dd, [J 2.] 3, 7. 4), 7.94 [(1H, ] s), 8. 09-8. 12 [(1H, ] m), 8. 52 [(1H, ] dd, [J 1. 0, ] 7.2), 8.65-8. 66 [(1H, ] m), 8. 88 [(1H, ] s); m/z (ES+) 342 [(100percent, ] [(MH]] +).A mixture of Step 2: Synthesis of 2-chloro-3-fluoro-4-(4-aminophenoxy)pyridine A solution of 4-aminophenol (24.8 g, 227 mmol) in anhydrous dimethyl sulfoxide (210 mL) was bubbled with nitrogen gas for 10 minutes, and potassium tert-butoxide (26.80 g, 238.8 mmol) was then added to get a reaction mixture. The reaction mixture was stirred at room temperature for 30 minutes, and then a) The mixture of 0.83 g (5.00 mmol) of a) The mixture of 0.83 g (5.00 mmol) of A solution of 0.95 g (3.34 mmol) of example XIII.1 , 0.59 g (3.52 mmol) 2, 4-dichloro-3-fluoro- pyridine and 1.90 g (13.7 mmol) K2C03 are added to 6 mL NMP and stirred at 80 C over night. The reaction is quenched by the addition water and extracted with EtOAc (3x). The combined organic layers are dried over MgS04, filtered and the solvent is removed in vacuo. The crude product is purified by HPLC (ACN/H20/FA). C19H2iCIFN302 (M= 377.8 g/mol) ESI-MS: 378 [M+H]+ Rt (HPLC):0.93 min (method D)

Molecular Weight:165.98
XLogP3:2.5
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