99% |
With ammonia In ethanol at 90℃; for 20h; |
I.1 Intermediate 1.1 : 2-amino-4-bromo-6-fluoro-benzonitrile
Intermediate 1.1 : 2-amino-4-bromo-6-fluoro-benzonitrile 5.0 g (22.9 mmol) 4-bromo-2,6-difluorobenzonitrile in 200 ml of a solution of NH3 in ethanol and heated in a pressure vessel to 90 °C for 20 h. After cooling to RT the solvent is evaporated and the residue taken up in water/DCM. The organic phase is separated, dried and evaporated. Yield: 4.9 g (99%), ESI-MS: m/z = 213/215 (M-H)", R,(HPLC): 1 .72 min (HPLC-S) |
99% |
With ammonia In ethanol at 90℃; for 20h; |
2-amino-4-bromo-6-fluoro-benzonitrile
5.0 g (22.9 mmol) 4-bromo-2,6-difluorobenzonitrile are dissolved in 200 ml of a solution of NH3 in ethanol and heated in a pressure vessel to 90 °C for 20 h. After cooling to RT the solvent is evaporated and the residual taken in up in water/DCM. The organic phase is separated, dried and evaporated. Yield: 4.9 g (99%), ESI-MS: m/z = 213/215 (M-H)", R,(HPLC): 1 .72 min (HPLC-R) |
99% |
With ammonia In ethanol at 90℃; for 20h; |
I.1 2-amino-4-bromo-6-fluoro-benzonitrile
5.0 g (22.9 mmol) 4-bromo-2,6-difluorobenzonitrile are dissolved in 200 ml of a solution of NH3 in ethanol and heated in a pressure vessel to 90° C. for 20 h. After cooling to RT the solvent is evaporated and the residual taken in up in water/DCM. The organic phase is separated, dried and evaporated. Yield: 4.9 g (99%), ESI-MS: m/z=213/215 (M-H)-, Rt(HPLC): 1.72 min (HPLC-R). |
98% |
With ammonia In ethanol at 100℃; Autoclave; |
|
92% |
With ammonium hydroxide In isopropanol at 80℃; for 12h; Sealed tube; |
120.1 Step 1: Synthesis of 2-amino-4-bromo-6-fluorobenzonitrile
Four separate reactions were run in parallel. For each reaction, to a solution of 4-bromo-2,6- difluorobenzonitrile (4.0 g, 18 mmol, 1 equiv) in iPrOH (40 mL) was added NH3•H2O (20 mL, 130 mmol, 25% w/w, 7 equiv). The resulting mixture was sealed and heated to 80 °C for 12 h then cooled to room temperature. The four separate reaction mixtures were combined and quenched with H2O (640 mL), and stirred for 15 min. The resulting solids were filtered, washed with H2O (100 mL), dissolved in toluene (3 x 10 mL) and concentrated under reduced pressure to afford 2-amino-4-bromo-6-fluorobenzonitrile (14.5 g, 92% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 6.74 (br s, 2H), 6.78 (dd, J = 9.26, 1.54 Hz, 1H), 6.82 (s, 1H). |
|
With ammonia In ethanol at 90℃; for 20h; |
Intermediate 1.1: 2-amino-4-bromo-6-fluoro-benzonitrile
5.0 g (22.9 mmcl) 4-bromo-2,6-difluorobenzonitrile in 200 ml of a solution of NH3 inethanol are heated in a pressure vessel to 9000 for 20 h. After cooling to RT the solvent is evaporated and the residue taken up in water/DCM. The organic phase is separated, dried and evaporated.Yield: 4.9 g (99%), ESI-MS: m/z = 213/215 (M-H), Rt(HPLC): 1 .72 mm (HPLC-S) |
23.2 g |
With ammonia In isopropanol at 90℃; for 16h; Sealed tube; Inert atmosphere; |
1 Step 1:
The 4-bromo-2,6-difluorobenzonitrile (25g, 0.11mol), Add ammonia (100mL) and isopropanol (60mL) to the sealed tube, The reaction system was stirred at 90°C for 16 hours. The reaction solution was cooled to room temperature and poured into water, A large amount of solids are separated out, filtered with suction, The filter cake was vacuum dried to obtain Intermediate 1-1 (23.2 g) as a gray solid. |