4-chloro-2-N-phenylbenzene-1,2-diamine

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

Procedure: A mixture of 4-chloro-N2-phenylbenzene-1,2-diamine (975 mg, 4.46 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (928 mg, 4.90 mmol), HOAt (668 mg, 4.90 mmol), 4-methylmorpholine (1.08 mL, 9.81 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (940 mg, 4.90 mmol) in DCM (30 mL) was stirred at RT for 19 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried and concentrated in vacuo to afford [(S)-1-(4-chloro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester as a purple solid (quantitative). A solution of the compound thus obtained (4.46 mmol) in AcOH (30 mL) was heated at 70° C. for 22 h. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic layer was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM) to afford the title compound as a yellow solid (1.20 g, 72% over two steps). LCMS (Method C): RT 3.82 min [M+H]+ 372.3 The reaction mixture was partitioned between DCM The organic layer was washed with brine dried concentrated in vacuo

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

Procedure: A mixture of 4-chloro-N2-phenylbenzene-1,2-diamine (975 mg, 4.46 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (928 mg, 4.90 mmol), HOAt (668 mg, 4.90 mmol), 4-methylmorpholine (1.08 mL, 9.81 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (940 mg, 4.90 mmol) in DCM (30 mL) was stirred at RT for 19 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried and concentrated in vacuo to afford [(S)-1-(4-chloro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester as a purple solid (quantitative). A solution of the compound thus obtained (4.46 mmol) in AcOH (30 mL) was heated at 70° C. for 22 h. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic layer was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM) to afford the title compound as a yellow solid (1.20 g, 72% over two steps). LCMS (Method C): RT 3.82 min [M+H]+ 372.3 The reaction mixture was partitioned between DCM The organic layer was washed with brine dried concentrated in vacuo

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

Procedure: To a mixture of (5-chloro-2-nitrophenyl)phenylamine (1.36 g, 5.47 mmol) in a 3:1 mixture of MeOH:water (120 mL) were added NH4Cl (1.76 g, 32.81 mmol) and iron powder (1.22 g, 21.88 mmol) and the reaction mixture heated at 90° C. for 2 h. After cooling to RT, the solid was filtered through a pad of Celite® and washed with additional MeOH. The filtrate was concentrated in vacuo and the resulting residue partitioned between EtOAc and water. The aqueous phase was further extracted with EtOAc and the combined organic fractions washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane) to afford the title compound as a brown oil (980 mg, 82%). LCMS (Method C): RT 3.57 min [M+H]+ 219.0 After cooling to RT the solid was filtered through a pad of Celite® washed with additional MeOH The filtrate was concentrated in vacuo the resulting residue partitioned between EtOAc and water The aqueous phase was further extracted with EtOAc the combined organic fractions washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane)

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

Procedure: To a mixture of (5-chloro-2-nitrophenyl)phenylamine (1.36 g, 5.47 mmol) in a 3:1 mixture of MeOH:water (120 mL) were added NH4Cl (1.76 g, 32.81 mmol) and iron powder (1.22 g, 21.88 mmol) and the reaction mixture heated at 90° C. for 2 h. After cooling to RT, the solid was filtered through a pad of Celite® and washed with additional MeOH. The filtrate was concentrated in vacuo and the resulting residue partitioned between EtOAc and water. The aqueous phase was further extracted with EtOAc and the combined organic fractions washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane) to afford the title compound as a brown oil (980 mg, 82%). LCMS (Method C): RT 3.57 min [M+H]+ 219.0 After cooling to RT the solid was filtered through a pad of Celite® washed with additional MeOH The filtrate was concentrated in vacuo the resulting residue partitioned between EtOAc and water The aqueous phase was further extracted with EtOAc the combined organic fractions washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane)

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

Procedure: A mixture of 4-chloro-N2-phenylbenzene-1,2-diamine (975 mg, 4.46 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (928 mg, 4.90 mmol), HOAt (668 mg, 4.90 mmol), 4-methylmorpholine (1.08 mL, 9.81 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (940 mg, 4.90 mmol) in DCM (30 mL) was stirred at RT for 19 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried and concentrated in vacuo to afford [(S)-1-(4-chloro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester as a purple solid (quantitative). A solution of the compound thus obtained (4.46 mmol) in AcOH (30 mL) was heated at 70° C. for 22 h. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic layer was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM) to afford the title compound as a yellow solid (1.20 g, 72% over two steps). LCMS (Method C): RT 3.82 min [M+H]+ 372.3 The reaction mixture was partitioned between DCM The organic layer was washed with brine dried concentrated in vacuo

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

Procedure: To a mixture of (5-chloro-2-nitrophenyl)phenylamine (1.36 g, 5.47 mmol) in a 3:1 mixture of MeOH:water (120 mL) were added NH4Cl (1.76 g, 32.81 mmol) and iron powder (1.22 g, 21.88 mmol) and the reaction mixture heated at 90° C. for 2 h. After cooling to RT, the solid was filtered through a pad of Celite® and washed with additional MeOH. The filtrate was concentrated in vacuo and the resulting residue partitioned between EtOAc and water. The aqueous phase was further extracted with EtOAc and the combined organic fractions washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane) to afford the title compound as a brown oil (980 mg, 82%). LCMS (Method C): RT 3.57 min [M+H]+ 219.0 After cooling to RT the solid was filtered through a pad of Celite® washed with additional MeOH The filtrate was concentrated in vacuo the resulting residue partitioned between EtOAc and water The aqueous phase was further extracted with EtOAc the combined organic fractions washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane)

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

Procedure: A mixture of 4-chloro-N2-phenylbenzene-1,2-diamine (975 mg, 4.46 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (928 mg, 4.90 mmol), HOAt (668 mg, 4.90 mmol), 4-methylmorpholine (1.08 mL, 9.81 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (940 mg, 4.90 mmol) in DCM (30 mL) was stirred at RT for 19 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried and concentrated in vacuo to afford [(S)-1-(4-chloro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester as a purple solid (quantitative). A solution of the compound thus obtained (4.46 mmol) in AcOH (30 mL) was heated at 70° C. for 22 h. After cooling to RT, the volatiles were removed in vacuo and the resulting residue partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic layer was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM) to afford the title compound as a yellow solid (1.20 g, 72% over two steps). LCMS (Method C): RT 3.82 min [M+H]+ 372.3 The reaction mixture was partitioned between DCM The organic layer was washed with brine dried concentrated in vacuo

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

Procedure: To a mixture of (5-chloro-2-nitrophenyl)phenylamine (1.36 g, 5.47 mmol) in a 3:1 mixture of MeOH:water (120 mL) were added NH4Cl (1.76 g, 32.81 mmol) and iron powder (1.22 g, 21.88 mmol) and the reaction mixture heated at 90° C. for 2 h. After cooling to RT, the solid was filtered through a pad of Celite® and washed with additional MeOH. The filtrate was concentrated in vacuo and the resulting residue partitioned between EtOAc and water. The aqueous phase was further extracted with EtOAc and the combined organic fractions washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane) to afford the title compound as a brown oil (980 mg, 82%). LCMS (Method C): RT 3.57 min [M+H]+ 219.0 After cooling to RT the solid was filtered through a pad of Celite® washed with additional MeOH The filtrate was concentrated in vacuo the resulting residue partitioned between EtOAc and water The aqueous phase was further extracted with EtOAc the combined organic fractions washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% DCM in cyclohexane)