methyl 3-(2-amino-5-bromoanilino)propanoate

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

Procedure: Sodium (2.4 g, 104 mmol) was added in portions to 50 mL of methanol until it dissolved. The solution was then added dropwise to a cooled solution of methyl 3-((2-amino-5-bromophenyl)amino)propanoate (9.4 g, 34.6 mmol) in 50 mL of methanol at 0° C. After additional, the mixture was stirred at room temperature overnight. It was concentrated, added with water (50 mL), extracted with ethyl acetate (50 mL) and purified by CombiFlash (PE:EA=5:1) to give 7-bromo-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one (2 g, yield 24%). LRMS (M+H)+: 240 m/z. 1H NMR (300 MHz, CDCl3) δ 2.68-2.72 (t, J=6.0 Hz, 2H), 3.68-3.72 (t, J=6.0 Hz, 2H), 6.79-6.82 (d, J=8.7 Hz, 2H), 6.98-7.06 (m, 2H), 8.00 (br, 1H). dissolved It was concentrated added with water (50 mL) extracted with ethyl acetate (50 mL) purified by CombiFlash (PE:EA=5:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iron powder (7 g, 0.12 mol) was added to a mixture of methyl 3-(5-bromo-2-nitrophenylamino)propanoate (12 g, 0.04 mol) in aq. NH4Cl solution (50 mL) and ethanol (100 mL). After heating at 60° C. for 2 h, the mixture solution was filtered. The filtrate was evaporated, diluted with water (100 mL), extracted with ethyl acetate (150 mL), dried and concentrated to give the crude product, which was purified by CombiFlash to afford methyl 3-((2-amino-5-bromophenyl)amino)propanoate (9.4 g, yield 84%). LRMS (M+H)+: 272 m/z. 1H NMR (300 MHz, CDCl3) δ 2.67-2.72 (d, 2H, J=6.3 Hz), 3.40-3.44 (d, 2H, J=6.3 Hz), 3.72 (s, 3H), 4.58 (br, 3H), 6.67-6.70 (d, 2H, J=8.1 Hz), 6.80-6.82 (m, 2H). the mixture solution was filtered The filtrate was evaporated diluted with water (100 mL) extracted with ethyl acetate (150 mL) dried concentrated to give the crude product, which was purified by CombiFlash