3-bromo-4-fluorobenzene-1,2-diamine

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL round-bottomed flask charged with 3-bromo-4-fluorobenzene-1,2-diamine (600c) (18 g, 88 mmol), DMF (100 mL), ethyl 2-bromopropionate (Sigma Aldrich, 11.54 mL, 89 mmol) and NaHCO3 (7.60 g powder, 90 mmol) was heated to 90° C. with a reflux condenser for 30 min, then at 120° C. for 15 h. The reaction mixture was cooled to RT, treated with brine and extracted with EtOAc (2×200 mL), washed with brine (3×) and dried over Na2SO4, filtered and concentrated affording crude 8-bromo-7-fluoro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one (21.75 g, 84 mmol, 96% yield) as an orange-brown viscous oil. The material was used in the subsequent step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.67 (s, 1H) 6.78-6.89 (m, 1H) 6.48-6.78 (m, 1H) 6.07-6.35 (m, 1H) 1.25 (d, J=6.46 Hz, 3H). 19F NMR (377 MHz, DMSO-d6) δ ppm −120.49 (1F, s). m/z (ESI, +ve ion) 259.0/261.0 (M+H)+. The reaction mixture was cooled to RT extracted with EtOAc (2×200 mL) washed with brine (3×) dried over Na2SO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL round-bottomed flask containing Pt/C (5%, 6.00 g, 1.54 mmol) and 2-bromo-3-fluoro-6-nitroaniline (600b) (20.85 g, 89 mmol) were treated with EtOH (250 mL) and stirred under an atmosphere of H2 (balloon) for 22 h. LC-MS indicated ca. 35% conversion to the desired material (M+1=204.9/206.9). Another balloon of H2 was added and it was stirred for another 16 h resulting in >90% conversion to the desired product (M+1=204.9/207.1) by LC-MS. The suspension was filtered through a plug of Celite washing with EtOH and concentrated affording crude 3-bromo-4-fluorobenzene-1,2-diamine (18 g, 88 mmol, 99% yield) as a black/purple viscous oil. 1H NMR (400 MHz, CDCl3) δ ppm 6.60 (1H, dd, J=8.5, 5.2 Hz), 6.42-6.50 (1H, m). 19F NMR (376 MHz, CDCl3) δ ppm −116.48 (1F, s). m/z (ESI, +ve ion) 204.9/206.9 (M+H)+. Another balloon of H2 was added it was stirred for another 16 h

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL round-bottomed flask containing Pt/C (5%, 6.00 g, 1.54 mmol) and 2-bromo-3-fluoro-6-nitroaniline (600b) (20.85 g, 89 mmol) were treated with EtOH (250 mL) and stirred under an atmosphere of H2 (balloon) for 22 h. LC-MS indicated ca. 35% conversion to the desired material (M+1=204.9/206.9). Another balloon of H2 was added and it was stirred for another 16 h resulting in >90% conversion to the desired product (M+1=204.9/207.1) by LC-MS. The suspension was filtered through a plug of Celite washing with EtOH and concentrated affording crude 3-bromo-4-fluorobenzene-1,2-diamine (18 g, 88 mmol, 99% yield) as a black/purple viscous oil. 1H NMR (400 MHz, CDCl3) δ ppm 6.60 (1H, dd, J=8.5, 5.2 Hz), 6.42-6.50 (1H, m). 19F NMR (376 MHz, CDCl3) δ ppm −116.48 (1F, s). m/z (ESI, +ve ion) 204.9/206.9 (M+H)+. Another balloon of H2 was added it was stirred for another 16 h

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL round-bottomed flask charged with 3-bromo-4-fluorobenzene-1,2-diamine (600c) (18 g, 88 mmol), DMF (100 mL), ethyl 2-bromopropionate (Sigma Aldrich, 11.54 mL, 89 mmol) and NaHCO3 (7.60 g powder, 90 mmol) was heated to 90° C. with a reflux condenser for 30 min, then at 120° C. for 15 h. The reaction mixture was cooled to RT, treated with brine and extracted with EtOAc (2×200 mL), washed with brine (3×) and dried over Na2SO4, filtered and concentrated affording crude 8-bromo-7-fluoro-3-methyl-3,4-dihydroquinoxalin-2(1H)-one (21.75 g, 84 mmol, 96% yield) as an orange-brown viscous oil. The material was used in the subsequent step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.67 (s, 1H) 6.78-6.89 (m, 1H) 6.48-6.78 (m, 1H) 6.07-6.35 (m, 1H) 1.25 (d, J=6.46 Hz, 3H). 19F NMR (377 MHz, DMSO-d6) δ ppm −120.49 (1F, s). m/z (ESI, +ve ion) 259.0/261.0 (M+H)+. The reaction mixture was cooled to RT extracted with EtOAc (2×200 mL) washed with brine (3×) dried over Na2SO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 mL round-bottomed flask containing Pt/C (5%, 6.00 g, 1.54 mmol) and 2-bromo-3-fluoro-6-nitroaniline (600b) (20.85 g, 89 mmol) were treated with EtOH (250 mL) and stirred under an atmosphere of H2 (balloon) for 22 h. LC-MS indicated ca. 35% conversion to the desired material (M+1=204.9/206.9). Another balloon of H2 was added and it was stirred for another 16 h resulting in >90% conversion to the desired product (M+1=204.9/207.1) by LC-MS. The suspension was filtered through a plug of Celite washing with EtOH and concentrated affording crude 3-bromo-4-fluorobenzene-1,2-diamine (18 g, 88 mmol, 99% yield) as a black/purple viscous oil. 1H NMR (400 MHz, CDCl3) δ ppm 6.60 (1H, dd, J=8.5, 5.2 Hz), 6.42-6.50 (1H, m). 19F NMR (376 MHz, CDCl3) δ ppm −116.48 (1F, s). m/z (ESI, +ve ion) 204.9/206.9 (M+H)+. Another balloon of H2 was added it was stirred for another 16 h