2-N-methylbenzene-1,2-diamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 4-benzyloxy-phenylamine (2 g, 8.4 mmol) in 30 mL of DCM was added triethylamine (1 mL) and di-2-pyridylthionocarbonate (2.5 g, 8.4 mmol). The resulting mixture was stirred at RT for 2 h. The reaction mixture was diluted with DCM and washed with water and brine. The organic layer was then dried over Na2SO4, filtered and concentrated. The residue was dissolved in 30 mL DMF, N-methyl-benzene-1,2-diamine (1.5 g, 12.7 mmol) and EDCI (2 g, 10.5 mmol). The resulting mixture was heated at 70° C. for 4 h. The reaction was cooled to RT, diluted with ethyl acetate and washed with water and brine. Purification by silica gel chromatography (98:2 chlorforma/MeOH) afforded the desired product (4-benzyloxy-phenyl)-(1-methyl-1H-benzoimidazol-2-yl)-amine. [M+1]=330.1 washed with water and brine The organic layer was then dried over Na2SO4 filtered concentrated The residue was dissolved in 30 mL DMF The resulting mixture was heated at 70° C. for 4 h The reaction was cooled to RT washed with water and brine Purification by silica gel chromatography (98:2 chlorforma/MeOH)

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

Procedure: To a solution of N-methyl-1,2-phenylenediamine (6.1 g, 4.99 mmol) in MeOH (50 mL) was added in portion of oxalacetic acid diethyl ester (9.9 g, 5.26 mmol). The mixture was then stirred at rt for 1 h. The precipitate was collected via filtration and was washed with small amount of methanol to yield a pale brownish solid as the pure product: 1H NMR (DMSO-d6) δ=11.1 (bs, 1H), 7.45–7.42 (m, 1H), 7.32–7.29 (m, 1H), 7.15–7.10 (m, 2H), 5.53 (s, 1H), 4.14 (q, J=9.0 Hz, 2H), 3.51 (s, 3H), 1.23 (t, J=9.0 Hz, 3H); HPLC (CH3CN—H2O-0.1% TFA) (short column): Rt=3.91 min. The precipitate was collected via filtration was washed with small amount of methanol to yield a pale brownish solid as the pure product

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-methyl-phenylenediamine (1 g, 8.2 mmol) and chloroacetic acid (0.9 g, 9.4 mol) were dissolved in 5 N aqueous hydrochloric acid (10 mL) and stirred at 55° C. overnight. The reaction mixture was then diluted with water and basified with solid sodium bicarbonate to give a precipitate which was filtered, washed with water and dried to provide the desired compound (1.3 g, 87%). to give a precipitate which was filtered washed with water dried

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-methyl-phenylenediamine (1 g, 8.2 mmol) and chloroacetic acid (0.9 g, 9.4 mol) were dissolved in 5 N aqueous hydrochloric acid (10 mL) and stirred at 55° C. overnight. The reaction mixture was then diluted with water and basified with solid sodium bicarbonate to give a precipitate which was filtered, washed with water and dried to provide the desired compound (1.3 g, 87%). to give a precipitate which was filtered washed with water dried

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-indolepropionic acid (2.85 g, 15 mmol) and N-methyl-1,2-phenylenediamine (611 mg, 5.0 mmol) was stirred at 130° C. for 5H, during which a dark brown viscous mass forms, which was dissolved in chloroform (100 ml). The organic solution was then washed with 10% strength Na2CO3 solution (2×30 ml) and water, dried over Na2SO4 and concentrated i. vac. and the residue was purified by flash chromatography with cyclohexane/EA (1:1). Yield: 863 mg (Ind-54, 63%), colourless solid The organic solution was then washed with 10% strength Na2CO3 solution (2×30 ml) and water dried over Na2SO4 concentrated i and the residue was purified by flash chromatography with cyclohexane/EA (1:1)

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-indolepropionic acid (2.85 g, 15 mmol) and N-methyl-1,2-phenylenediamine (611 mg, 5.0 mmol) was stirred at 130° C. for 5H, during which a dark brown viscous mass forms, which was dissolved in chloroform (100 ml). The organic solution was then washed with 10% strength Na2CO3 solution (2×30 ml) and water, dried over Na2SO4 and concentrated i. vac. and the residue was purified by flash chromatography with cyclohexane/EA (1:1). Yield: 863 mg (Ind-54, 63%), colourless solid The organic solution was then washed with 10% strength Na2CO3 solution (2×30 ml) and water dried over Na2SO4 concentrated i and the residue was purified by flash chromatography with cyclohexane/EA (1:1)

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

Procedure: A suspension of 940 mg (2.0 mMol) of tert.-butyl 4'-[(2-n-propyl-6-carboxy-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate and 320 mg (2.0 mMol) of carbonyldiimidazole in a solution of 1.0 ml of triethylamine in 30 ml of tetrahydrofuran is stirred for 30 minutes at ambient temperature, then 250 mg (2.0 mMol) of 2-methylaminoaniline are added and the mixture is stirred for a further 16 hours. It is then evaporated to dryness and the residue is refluxed in 20 ml of phosphorus oxychloride, with stirring, for 1 hour. The majority of the phosphorus oxychloride is then distilled off, the dark, greasy residue is decomposed with 30 ml of water, the strongly acidic suspension thus obtained is refluxed for about 1 hour, adjusted to pH 6 after cooling and then concentrated by evaporation. The crude product obtained is purified by column chromatography (120 g of silica gel, eluant:methylene chloride/methanol=15:1). the mixture is stirred for a further 16 hours It is then evaporated to dryness the residue is refluxed in 20 ml of phosphorus oxychloride with stirring, for 1 hour The majority of the phosphorus oxychloride is then distilled off the strongly acidic suspension thus obtained is refluxed for about 1 hour after cooling concentrated by evaporation