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

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

Procedure: The title compound was prepared in accordance with the general method of Example 191(C), from N1-isopropylbenzene-1,2-diamine (3.88 g, 25.82 mmol)-1) and 2-chloroacetic acid (3.70 g, 39 mmol). The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent) to afford 2.05 g of 2-(chloromethyl)-1-isopropyl-1H-benzo[d]imidazole (Yield: 38%) as a light brown oil. The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent)

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

Procedure: The title compound was prepared in accordance with the general method of Example 191(C), from N1-isopropylbenzene-1,2-diamine (3.88 g, 25.82 mmol) and 2-chloroacetic acid (3.70 g, 39 mmol). The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent) to afford 2.05 g of 2-(chloromethyl)-1-isopropyl-1H-benzo[d]imidazole (Yield: 38%) as a light brown oil. The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent)

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

Procedure: N-isopropyl-o-phenylenediamine (2.8 g, 18.6 mmol), which is a known compound, was reacted with monochloroacetic acid (2.64 g, 28 mmol) in hydrochloric acid. The reaction mixture was made to weak by alkaline alkali with aqueous ammonia and the obtained oily material was refined in a usual manner to give the title intermediate (2.5 g, 12 mmol).

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of ethanol (600 mL) and 2 M sodium hydroxide solution (320 mL) cooled in an ice bath was added Zn dust (59.5 g) slowly. While stirring the Zn slurry, N-isopropyl-N-(2-nitrophenyl)amine (41 g, 0.228 mol) dissolved in ethanol (50 mL) was added. The mixture was stirred at 0° C. for 30 min, then heated to 85° C. The mixture was stirred at 85° C. for about 12 h until the refluxing solution of the mixture became a colorless solution. The mixture was then cooled to 0° C. and filtered. The collected solid was rinsed with ethyl acetate (200 mL). The filtrate and rinsed solution were combined, and evaporated in vacuo to remove excess volatile solvents. During the concentration, the mixture became pale brown/yellow. The aqueous concentrate was extracted with ethyl acetate (800 mL). The organic solution was concentrated to dryness, to provide the title intermediate (33 g) as a brown-pink oil which was used in the next step without further treatment. 1H-NMR (CDCl3, 300 MHz): 6 (ppm) 6.73-6.5 (m, 4H), 3.58-3.55 (hept, 1H), 1.2 (d, 6H). cooled in an ice bath was added heated to 85° C The mixture was stirred at 85° C. for about 12 h until the refluxing solution of the mixture The mixture was then cooled to 0° C. filtered The collected solid was rinsed with ethyl acetate (200 mL) The filtrate and rinsed solution evaporated in vacuo to remove excess volatile solvents During the concentration The aqueous concentrate was extracted with ethyl acetate (800 mL) The organic solution was concentrated to dryness

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

Procedure: The title compound was prepared in accordance with the general method of Example 191(C), from N1-isopropylbenzene-1,2-diamine (3.88 g, 25.82 mmol)-1) and 2-chloroacetic acid (3.70 g, 39 mmol). The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent) to afford 2.05 g of 2-(chloromethyl)-1-isopropyl-1H-benzo[d]imidazole (Yield: 38%) as a light brown oil. The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent)

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

Procedure: The title compound was prepared in accordance with the general method of Example 191(C), from N1-isopropylbenzene-1,2-diamine (3.88 g, 25.82 mmol)-1) and 2-chloroacetic acid (3.70 g, 39 mmol). The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent) to afford 2.05 g of 2-(chloromethyl)-1-isopropyl-1H-benzo[d]imidazole (Yield: 38%) as a light brown oil. The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent)

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

Procedure: The title compound was prepared in accordance with the general method of Example 191(C), from N1-isopropylbenzene-1,2-diamine (3.88 g, 25.82 mmol) and 2-chloroacetic acid (3.70 g, 39 mmol). The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent) to afford 2.05 g of 2-(chloromethyl)-1-isopropyl-1H-benzo[d]imidazole (Yield: 38%) as a light brown oil. The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent)

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

Procedure: The title compound was prepared in accordance with the general method of Example 191(C), from N1-isopropylbenzene-1,2-diamine (3.88 g, 25.82 mmol) and 2-chloroacetic acid (3.70 g, 39 mmol). The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent) to afford 2.05 g of 2-(chloromethyl)-1-isopropyl-1H-benzo[d]imidazole (Yield: 38%) as a light brown oil. The crude residue was purified over silicagel chromatography (prepacked 85 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent)

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

Procedure: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (EDC, 206 mg, 1.34 mmol) is added to a solution of N1-isopropylbenzene-1,2-diamine (100 mg, 0.67 mmol) and methyl 4-isothiocyanatobenzoate (138 mg, 0.67 mmol) in tetrahydrofuran. The reaction may be heated to reflux for a time period (for example 2 hours) and cooled to room temperature. The mixture may be diluted with ethyl acetate, filtered and concentrated. The residue may be purified by any method, including Biotage column chromatography to give methyl 4-(1-isopropyl-1H-benzo[d]imidazol-2-ylamino)benzoate (122 mg) The reaction may be heated to reflux for a time period (for example 2 hours) filtered concentrated The residue may be purified by any method

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

Procedure: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (EDC, 206 mg, 1.34 mmol) is added to a solution of N1-isopropylbenzene-1,2-diamine (100 mg, 0.67 mmol) and methyl 4-isothiocyanatobenzoate (138 mg, 0.67 mmol) in tetrahydrofuran. The reaction may be heated to reflux for a time period (for example 2 hours) and cooled to room temperature. The mixture may be diluted with ethyl acetate, filtered and concentrated. The residue may be purified by any method, including Biotage column chromatography to give methyl 4-(1-isopropyl-1H-benzo[d]imidazol-2-ylamino)benzoate (122 mg) The reaction may be heated to reflux for a time period (for example 2 hours) filtered concentrated The residue may be purified by any method

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

Procedure: Ammonium formate (960 mg, 15.0 mmol) is added to a solution of N-isopropyl-2-nitroaniline (550 mg, 3.03 mmol) in methanol. This may be followed by a catalytic amount of palladium on carbon (5%). The mixture may be refluxed overnight, cooled to room temperature and filtered. The filtrate may be concentrated by any applicable and the residue may be purified, for example by Biotage column chromatography to give N1-isopropylbenzene-1,2-diamine (398 mg) The mixture may be refluxed overnight filtered The filtrate may be concentrated by any applicable and the residue

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

Procedure: Ammonium formate (960 mg, 15.0 mmol) is added to a solution of N-isopropyl-2-nitroaniline (550 mg, 3.03 mmol) in methanol. This may be followed by a catalytic amount of palladium on carbon (5%). The mixture may be refluxed overnight, cooled to room temperature and filtered. The filtrate may be concentrated by any applicable and the residue may be purified, for example by Biotage column chromatography to give N1-isopropylbenzene-1,2-diamine (398 mg) The mixture may be refluxed overnight filtered The filtrate may be concentrated by any applicable and the residue