5-BROMO-2,3-DIAMINOFLUOROBENZENE

Intermediate 14; 5 -bromo-3 -fluorobenzene- 1 , 2 -diamine; To a solution of 4-bromo-2-fluoro-6-nitroaniline (0.5 g, 2.1 mmol) in THF (4.6 mL), EtOH (4.6 mL) and H5.00 g (21.275 mmol) of 4-bromo-2fluoro-6-nitroaniline was dissolved in 190 ml ethanol, 19.20 g (85.100 mmol) of tin(II) chloride dihydrate was added and it was stirred overnight at 70The 4 - bromo -2 - fluoro -6 - nitroaniline (1.5 g, 6.3 mmol), iron powder (1.8 g, 31.8 mmol) and ammonium chloride (5.1 g, 96.0 mmol) dissolved in ethanol (15 ml), tetrahydrofuran (15 ml) and water (5 ml) in the, and heated to 90 °C stirring 2 h. The reaction cooled to room temperature, filtered, the filtrate is concentrated, the crude product of the title compound obtained (1.69 g), without purification directly used for the next step reaction.A solution of sodium nitrite (1.85 g, 26.8 mmol) in water (50 mL) was added to a solution of 5-Bromo-3-fluoro-benzene-l, 2-diamine (1.07 g, 5.2 mmol), ie/ -butyl 4-(2- bromoacetyl)piperidine-l-carboxylate (1.60 g, 5.2 mmol), and DMF (80 mL) were combined and stirred at room temperature for 16 h, 50 °C for 24 h, and 70 °C for 24 h. After cooling to room temperature, potassium carbonate (1.08 g, 7.84 mmol) and di-ie/ -butyl dicarbonate (1.4 mL, 6.3 mmol) were added. The reaction mixture was stirred at room temperature for 2 h. The mixture was partitioned between EtOAc and brine. The organic layer was washed twice with brine, dried over Na2S04, filtered and concentrated. The residue was chromatographed on silica gel, eluting with 0-100percent EtOAc in hexanes to yield ieri-butyl 4-(6-bromo-8-fluoro-quinoxalin-2- yl)piperidine-l-carboxylate and ie/ -butyl 4-(7-bromo-5-fluoroquinoxalin-2-yl)piperidine-l- carboxylate as an approximate 1 : 1 mixture (labeled distinguishable peaks as compounds A and B in 1H NMR; labeled overlapping peaks as apparent peaks 'apt') (1.23 g, 58percent). MS m/z 310.2 [M+H-C02-i-Bu]+; 1H NMR (CDC13) delta: 8.84 (s, 1H, A), 8.82 (s, 1H, B), 8.12 (t, 7 = 1.7 Hz, 1H, A), 8.09 (t, 7 = 1.7 Hz, 1H, B), 7.61 (dd, 7 = 9.2, 2.1 Hz, 1H, A), 7.58 (dd, 7 = 9.0, 2.0 Hz, 1H, B), 4.34 (apt d, 7 = 12.2 Hz, 4H), 3.17 (apt qt, 7 = 11.9, 3.7 Hz, 2H), 2.94 (apt br tt, 7 = 13.1, 2.8 Hz, 4H), 1.99 - 2.06 (m, 4H), 1.93 (apt quint 7 = 11.6, 4.0 Hz, 4H), 1.51 (apt d, 7 = 1.8 Hz, 18H).

Molecular Weight:205.03
XLogP3:1.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:203.96984
Monoisotopic Mass:203.96984
Topological Polar Surface Area:52
Heavy Atom Count:10
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes