4-fluoro-2-N-propan-2-ylbenzene-1,2-diamine

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

Verfahren: 4-Fluoro-N2-isopropylbenzene-1,2-diamine (0.7 g, 5.07 mmol) was dissolved in DCM (10 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.06 g, 5.58 mmol) added. To the resultant dark red solution was added HOAt (0.76 g, 5.58 mmol), followed by N-methyl morpholine (1.23 mL, 11.15 mmol) and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.07 g, 5.58 mmol). The resultant blue/black solution was stirred at RT overnight, under an atmosphere of nitrogen. The mixture was diluted with DCM (40 mL) and washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organic fraction was dried (MgSO4), filtered and concentrated in vacuo to afford a dark red oil. This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which solidified on standing. This was dissolved in acetic acid (20 mL) and heated at 70° C. overnight. The resultant mixture was allowed to cool to RT and was concentrated in vacuo to afford the title compound as a dark red gum (1.0 g, 88%). This material was used in the next step without any purification. LCMS (Method B): RT 2.78 min [M+H]+ 322.2 washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL) The organic fraction was dried (MgSO4) filtered concentrated in vacuo to afford a dark red oil This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which heated at 70° C. overnight to cool to RT was concentrated in vacuo

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

Verfahren: 4-Fluoro-N2-isopropylbenzene-1,2-diamine (0.7 g, 5.07 mmol) was dissolved in DCM (10 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.06 g, 5.58 mmol) added. To the resultant dark red solution was added HOAt (0.76 g, 5.58 mmol), followed by N-methyl morpholine (1.23 mL, 11.15 mmol) and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.07 g, 5.58 mmol). The resultant blue/black solution was stirred at RT overnight, under an atmosphere of nitrogen. The mixture was diluted with DCM (40 mL) and washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organic fraction was dried (MgSO4), filtered and concentrated in vacuo to afford a dark red oil. This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which solidified on standing. This was dissolved in acetic acid (20 mL) and heated at 70° C. overnight. The resultant mixture was allowed to cool to RT and was concentrated in vacuo to afford the title compound as a dark red gum (1.0 g, 88%). This material was used in the next step without any purification. LCMS (Method B): RT 2.78 min [M+H]+ 322.2 washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL) The organic fraction was dried (MgSO4) filtered concentrated in vacuo to afford a dark red oil This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which heated at 70° C. overnight to cool to RT was concentrated in vacuo

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

Verfahren: (5-Fluoro-2-nitrophenyl)isopropylamine (2.1 g, 12.6 mmol) was dissolved in EtOAc (60 mL) and the flask evacuated and flushed with nitrogen gas, prior to the addition of 10% Pd/C (0.21 g). The mixture was stirred under an atmosphere of hydrogen gas overnight. A further amount of 10% Pd/C (0.21 g) was added and the mixture was stirred under an atmosphere of hydrogen for a further 3 h. A further amount of 10% Pd/C (0.21 g) was added and the mixture stirred under an atmosphere of hydrogen for a further 2 h. The resultant mixture was filtered through Celite® under an atmosphere of nitrogen and the filtrate concentrated in vacuo to afford the title compound as a dark red oil (1.5 g, 88%). 1H NMR (CDCl3, 400 MHz): δ 6.62 (1H, dd, J=8.34, 5.72 Hz), 6.36 (1H, dd, J=11.17, 2.77 Hz), 6.28 (1H, td, J=8.43, 2.75 Hz), 3.61-3.47 (1H, m), 1.24 (6H, d, J=6.27 Hz) the flask evacuated flushed with nitrogen gas to the addition of 10% Pd/C (0.21 g) A further amount of 10% Pd/C (0.21 g) was added the mixture was stirred under an atmosphere of hydrogen for a further 3 h A further amount of 10% Pd/C (0.21 g) was added the mixture stirred under an atmosphere of hydrogen for a further 2 h The resultant mixture was filtered through Celite® under an atmosphere of nitrogen the filtrate concentrated in vacuo

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

Verfahren: (5-Fluoro-2-nitrophenyl)isopropylamine (2.1 g, 12.6 mmol) was dissolved in EtOAc (60 mL) and the flask evacuated and flushed with nitrogen gas, prior to the addition of 10% Pd/C (0.21 g). The mixture was stirred under an atmosphere of hydrogen gas overnight. A further amount of 10% Pd/C (0.21 g) was added and the mixture was stirred under an atmosphere of hydrogen for a further 3 h. A further amount of 10% Pd/C (0.21 g) was added and the mixture stirred under an atmosphere of hydrogen for a further 2 h. The resultant mixture was filtered through Celite® under an atmosphere of nitrogen and the filtrate concentrated in vacuo to afford the title compound as a dark red oil (1.5 g, 88%). 1H NMR (CDCl3, 400 MHz): δ 6.62 (1H, dd, J=8.34, 5.72 Hz), 6.36 (1H, dd, J=11.17, 2.77 Hz), 6.28 (1H, td, J=8.43, 2.75 Hz), 3.61-3.47 (1H, m), 1.24 (6H, d, J=6.27 Hz) the flask evacuated flushed with nitrogen gas to the addition of 10% Pd/C (0.21 g) A further amount of 10% Pd/C (0.21 g) was added the mixture was stirred under an atmosphere of hydrogen for a further 3 h A further amount of 10% Pd/C (0.21 g) was added the mixture stirred under an atmosphere of hydrogen for a further 2 h The resultant mixture was filtered through Celite® under an atmosphere of nitrogen the filtrate concentrated in vacuo

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

Verfahren: 4-Fluoro-N2-isopropylbenzene-1,2-diamine (0.7 g, 5.07 mmol) was dissolved in DCM (10 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.06 g, 5.58 mmol) added. To the resultant dark red solution was added HOAt (0.76 g, 5.58 mmol), followed by N-methyl morpholine (1.23 mL, 11.15 mmol) and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.07 g, 5.58 mmol). The resultant blue/black solution was stirred at RT overnight, under an atmosphere of nitrogen. The mixture was diluted with DCM (40 mL) and washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organic fraction was dried (MgSO4), filtered and concentrated in vacuo to afford a dark red oil. This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which solidified on standing. This was dissolved in acetic acid (20 mL) and heated at 70° C. overnight. The resultant mixture was allowed to cool to RT and was concentrated in vacuo to afford the title compound as a dark red gum (1.0 g, 88%). This material was used in the next step without any purification. LCMS (Method B): RT 2.78 min [M+H]+ 322.2 washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL) The organic fraction was dried (MgSO4) filtered concentrated in vacuo to afford a dark red oil This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which heated at 70° C. overnight to cool to RT was concentrated in vacuo

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

Verfahren: (5-Fluoro-2-nitrophenyl)isopropylamine (2.1 g, 12.6 mmol) was dissolved in EtOAc (60 mL) and the flask evacuated and flushed with nitrogen gas, prior to the addition of 10% Pd/C (0.21 g). The mixture was stirred under an atmosphere of hydrogen gas overnight. A further amount of 10% Pd/C (0.21 g) was added and the mixture was stirred under an atmosphere of hydrogen for a further 3 h. A further amount of 10% Pd/C (0.21 g) was added and the mixture stirred under an atmosphere of hydrogen for a further 2 h. The resultant mixture was filtered through Celite® under an atmosphere of nitrogen and the filtrate concentrated in vacuo to afford the title compound as a dark red oil (1.5 g, 88%). 1H NMR (CDCl3, 400 MHz): δ 6.62 (1H, dd, J=8.34, 5.72 Hz), 6.36 (1H, dd, J=11.17, 2.77 Hz), 6.28 (1H, td, J=8.43, 2.75 Hz), 3.61-3.47 (1H, m), 1.24 (6H, d, J=6.27 Hz) the flask evacuated flushed with nitrogen gas to the addition of 10% Pd/C (0.21 g) A further amount of 10% Pd/C (0.21 g) was added the mixture was stirred under an atmosphere of hydrogen for a further 3 h A further amount of 10% Pd/C (0.21 g) was added the mixture stirred under an atmosphere of hydrogen for a further 2 h The resultant mixture was filtered through Celite® under an atmosphere of nitrogen the filtrate concentrated in vacuo

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

Verfahren: 4-Fluoro-N2-isopropylbenzene-1,2-diamine (0.7 g, 5.07 mmol) was dissolved in DCM (10 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.06 g, 5.58 mmol) added. To the resultant dark red solution was added HOAt (0.76 g, 5.58 mmol), followed by N-methyl morpholine (1.23 mL, 11.15 mmol) and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.07 g, 5.58 mmol). The resultant blue/black solution was stirred at RT overnight, under an atmosphere of nitrogen. The mixture was diluted with DCM (40 mL) and washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organic fraction was dried (MgSO4), filtered and concentrated in vacuo to afford a dark red oil. This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which solidified on standing. This was dissolved in acetic acid (20 mL) and heated at 70° C. overnight. The resultant mixture was allowed to cool to RT and was concentrated in vacuo to afford the title compound as a dark red gum (1.0 g, 88%). This material was used in the next step without any purification. LCMS (Method B): RT 2.78 min [M+H]+ 322.2 washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL) The organic fraction was dried (MgSO4) filtered concentrated in vacuo to afford a dark red oil This was purified by column chromatography (silica gel, gradient 0-20% EtOAc in DCM) to afford a red oil which heated at 70° C. overnight to cool to RT was concentrated in vacuo

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

Verfahren: (5-Fluoro-2-nitrophenyl)isopropylamine (2.1 g, 12.6 mmol) was dissolved in EtOAc (60 mL) and the flask evacuated and flushed with nitrogen gas, prior to the addition of 10% Pd/C (0.21 g). The mixture was stirred under an atmosphere of hydrogen gas overnight. A further amount of 10% Pd/C (0.21 g) was added and the mixture was stirred under an atmosphere of hydrogen for a further 3 h. A further amount of 10% Pd/C (0.21 g) was added and the mixture stirred under an atmosphere of hydrogen for a further 2 h. The resultant mixture was filtered through Celite® under an atmosphere of nitrogen and the filtrate concentrated in vacuo to afford the title compound as a dark red oil (1.5 g, 88%). 1H NMR (CDCl3, 400 MHz): δ 6.62 (1H, dd, J=8.34, 5.72 Hz), 6.36 (1H, dd, J=11.17, 2.77 Hz), 6.28 (1H, td, J=8.43, 2.75 Hz), 3.61-3.47 (1H, m), 1.24 (6H, d, J=6.27 Hz) the flask evacuated flushed with nitrogen gas to the addition of 10% Pd/C (0.21 g) A further amount of 10% Pd/C (0.21 g) was added the mixture was stirred under an atmosphere of hydrogen for a further 3 h A further amount of 10% Pd/C (0.21 g) was added the mixture stirred under an atmosphere of hydrogen for a further 2 h The resultant mixture was filtered through Celite® under an atmosphere of nitrogen the filtrate concentrated in vacuo