4-fluoro-6-methylbenzene-1,3-diamine

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8 g 5-fluoro-2,4-diaminotoluene from Step 2 are dissolved in 250 ml pyridine, mixed with 7.9 ml benzenesulfonyl chloride, and stirred for 1 hour at 120° C. After cooling, the reaction preparation is poured over ice. The obtained precipitate is washed with water, dried in vacuum over phosphorus pentoxide, and recrystallized from methanol. 3.9 g (41% of theory) 5-fluoro-2,4-bis[(N-benzenesulfonyl)amino]toluene are obtained which melts at 146° C. After cooling the reaction preparation is poured over ice The obtained precipitate is washed with water dried in vacuum over phosphorus pentoxide recrystallized from methanol

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8 g 5-fluoro-2,4-diaminotoluene from Step 2 are dissolved in 250 ml pyridine, mixed with 7.9 ml benzenesulfonyl chloride, and stirred for 1 hour at 120° C. After cooling, the reaction preparation is poured over ice. The obtained precipitate is washed with water, dried in vacuum over phosphorus pentoxide, and recrystallized from methanol. 3.9 g (41% of theory) 5-fluoro-2,4-bis[(N-benzenesulfonyl)amino]toluene are obtained which melts at 146° C. After cooling the reaction preparation is poured over ice The obtained precipitate is washed with water dried in vacuum over phosphorus pentoxide recrystallized from methanol

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

Procedure: 2 g (0.01 ml) 5-fluoro-2,4-dinitrotoluene from Step 1 are hydrated with catalytic amounts of palladium/carbon (10% Pd) in 50 ml absolute ethanol. After removing the catalyst by filtration, the solvent is completely removed by distillation and the obtained product is recrystallized from toluene. 0.7 g (50% of theory) 5-fluoro-2,4-diaminotoluene are obtained which melts at 112° C. accompanied by decomposition. After removing the catalyst by filtration the solvent is completely removed by distillation the obtained product is recrystallized from toluene

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of carbonic acid 4-nitro-phenyl ester 2-trimethylsilanyl-ethyl ester (566 mg, 2 mmol) in DMF (4 ml) at 23° C. under an atmosphere of argon was added DMAP (12 mg, 0.1 mmol), DIEA (0.35 ml, 2 mmol) and 4-fluoro-6-methyl-benzene-1,3-diamine. The resulting solution was heated to 50° C. for 48 h. The reaction mixture was quenched with saturated NaHCO3 (aq), extracted with EtOAc (3×20 ml). The EtOAc was removed in-vacuo, and the residue was re-dissolved in Et2O then washed with 3 N NaOH (aq), water, brine, dried with Na2SO4, filtered and concentrated. Purification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane) gave (5-amino-4-fluoro-2-methyl-phenyl)-carbamic acid 2-trimethylsilanyl-ethyl ester (160 mg, 28%). MS (ESI+) [M+H]/z Calc'd 634. found 634. The reaction mixture was quenched with saturated NaHCO3 (aq) extracted with EtOAc (3×20 ml) The EtOAc was removed in-vacuo the residue was re-dissolved in Et2O then washed with 3 N NaOH (aq), water, brine dried with Na2SO4 filtered concentrated Purification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane)

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

Procedure: A mixture of 1-fluoro-5-methyl-2,4-dinitro-benzene (1.0 g, 5 mmol) and 10% Pd/C (200 mg) in MeOH (20 ml) was hydrogenated at 23° C. for 24 h. The reaction mixture was filtered through celite and concentrated. Purification by silica gel chromatography (1:1 ethyl acetate-hexane) gave 4-fluoro-6-methyl-benzene-1,3-diamine (613 mg, 87%). The reaction mixture was filtered through celite and concentrated Purification by silica gel chromatography (1:1 ethyl acetate-hexane)

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

Procedure: A mixture of 1-fluoro-5-methyl-2,4-dinitro-benzene (1.0 g, 5 mmol) and 10% Pd/C (200 mg) in MeOH (20 ml) was hydrogenated at 23° C. for 24 h. The reaction mixture was filtered through celite and concentrated. Purification by silica gel chromatography (1:1 ethyl acetate-hexane) gave 4-fluoro-6-methyl-benzene-1,3-diamine (613 mg, 87%). The reaction mixture was filtered through celite and concentrated Purification by silica gel chromatography (1:1 ethyl acetate-hexane)

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

Procedure: 2 g (0.01 ml) of 5-fluoro-2,4-dinitrotoluene from Step 1 are hydrated with catalytic amounts of palladium/carbon (10% Pd) in 50 ml absolute ethanol. After the catalyst is removed by filtration, the solvent is distilled off completely and the obtained product is recrystallized from toluene. 0.7 g (50 % of theory) of 5-fluoro-2,4-diaminotoluene is obtained which melts at 112° Celsius accompanied by decomposition. After the catalyst is removed by filtration the solvent is distilled off completely the obtained product is recrystallized from toluene

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

Procedure: 2 g (0.01 ml) of 5-fluoro-2,4-dinitrotoluene from Step 1 are hydrated with catalytic amounts of palladium/carbon (10% Pd) in 50 ml absolute ethanol. After the catalyst is removed by filtration, the solvent is distilled off completely and the obtained product is recrystallized from toluene. 0.7 g (50 % of theory) of 5-fluoro-2,4-diaminotoluene is obtained which melts at 112° Celsius accompanied by decomposition. After the catalyst is removed by filtration the solvent is distilled off completely the obtained product is recrystallized from toluene

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

Procedure: A mixture of 1-fluoro-5-methyl-2,4-dinitro-benzene (1.0 g, 5 mmol) and 10% Pd/C (200 mg) in MeOH (20 ml) was hydrogenated at 23° C. for 24 h. The reaction mixture was filtered through celite and concentrated. Purification by silica gel chromatography (1:1 ethyl acetate-hexane) gave 4-fluoro-6-methyl-benzene-1,3-diamine (613 mg, 87%). The reaction mixture was filtered through celite and concentrated Purification by silica gel chromatography (1:1 ethyl acetate-hexane)

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

Procedure: A mixture of 1-fluoro-5-methyl-2,4-dinitro-benzene (1.0 g, 5 mmol) and 10% Pd/C (200 mg) in MeOH (20 ml) was hydrogenated at 23° C. for 24 h. The reaction mixture was filtered through celite and concentrated. Purification by silica gel chromatography (1:1 ethyl acetate-hexane) gave 4-fluoro-6-methyl-benzene-1,3-diamine (613 mg, 87%). The reaction mixture was filtered through celite and concentrated Purification by silica gel chromatography (1:1 ethyl acetate-hexane)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of carbonic acid 4-nitro-phenyl ester 2-trimethylsilanyl-ethyl ester (566 mg, 2 mmol) in DMF (4 ml) at 23° C. under an atmosphere of argon was added DMAP (12 mg, 0.1 mmol), DIEA (0.35 ml, 2 mmol) and 4-fluoro-6-methyl-benzene-1,3-diamine. The resulting solution was heated to 50° C. for 48 h. The reaction mixture was quenched with saturated NaCHO3 (aq), extracted with EtOAc (3×20 ml). The EtOAc was removed in-vacuo, and the residue was re-dissolved in Et2O then washed with 3 N NaOH (aq), water, brine, dried with Na2SO4, filtered and concentrated. Purification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane) gave (5-amino-4-fluoro-2-methyl-phenyl)-carbamic acid 2-trimethylsilanyl-ethyl ester (160 mg, 28%). MS (ESI+) [M+H]/z Calc'd 634, found 634. The reaction mixture was quenched with saturated NaCHO3 (aq) extracted with EtOAc (3×20 ml) The EtOAc was removed in-vacuo the residue was re-dissolved in Et2O then washed with 3 N NaOH (aq), water, brine dried with Na2SO4 filtered concentrated Purification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane)

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

Procedure: A mixture of 1-fluoro-5-methyl-2,4-dinitro-benzene (1.0 g, 5 mmol) and 10% Pd/C (200 mg) in MeOH (20 ml) was hydrogenated at 23° C. for 24 h. The reaction mixture was filtered through celite and concentrated. Purification by silica gel chromatography (1:1 ethyl acetate-hexane) gave 4-fluoro-6-methyl-benzene-1,3-diamine (613 mg, 87%). The reaction mixture was filtered through celite and concentrated Purification by silica gel chromatography (1:1 ethyl acetate-hexane)