3,4-dimethylbenzene-1,2-diamine

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

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

Procedure: 2-(4-Nitrophenyl)-4,5-dimethyl benzimidazole was prepared by mixing 1,2-diamino-3,4-dimethylbenzene (1.36 g, 9.8 mmole) with 4-nitrobenzoic acid (1.67 g, 9.8 mmole) and dissolved in POCl3 (10 ml) and heated to reflux for 2.5 hours. The reaction mixture was cooled and cautiously poured onto ice. The resulting solid was filtered, washed with NaHCO3 and used without further purification. heated to reflux for 2.5 hours The reaction mixture was cooled cautiously poured onto ice The resulting solid was filtered washed with NaHCO3 used without further purification

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

Procedure: The compound was prepared in a manner analogous to 2,6-dichloro-N-[3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-benzamide (Example 94E), but using 4-(2,6-difluoro-benzoylamino)-1H-pyrazole-3-carboxylic acid (Example 16D) and 3,4-dimethyl-1,2-phenylene diamine to give N-[3-(4,5-dimethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-2,6-difluoro-benzamide (89 mg) as a pale orange solid. (LC/MS: Rt 2.98, [M+H]+ 368.15).

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

Procedure: To a 125 mL round bottom flask 2.20 g of 2,3-dimethyl-6-nitro-aniline (13.2 mmol) was added. Then 15 mL of ethanol was added to the flask followed by the addition of 4 mL of 20 wt % NaOH in water. Then 2.0 g of zinc dust was added to the flask. The flask was fitted with a condenser and was left to reflux with stirring. After about 0.5 hours the mixture became very pale-brown. After refluxing for 18 hours the mixture was filtered hot to give a pale filtrate which quickly became dark red. C8H12N2, fw=136.19. Yield 1.78 g, 98.7%. Mp: 60° C. (melt). 1H NMR (300 MHz, CDCl3): δ 6.54(s, 2H), 3.46 (br s, 2H), 3.21 (br s, 2H), 2.22 (s, 3H), 2.11 (s, 3H). Rf=0.68 (ethyl acetate/silica). The flask was fitted with a condenser was left to reflux After refluxing for 18 hours the mixture was filtered hot to give a pale filtrate which quickly became dark red

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

Procedure: To a 125 mL round bottom flask 2.20 g of 2,3-dimethyl-6-nitro-aniline (13.2 mmol) was added. Then 15 mL of ethanol was added to the flask followed by the addition of 4 mL of 20 wt % NaOH in water. Then 2.0 g of zinc dust was added to the flask. The flask was fitted with a condenser and was left to reflux with stirring. After about 0.5 hours the mixture became very pale-brown. After refluxing for 18 hours the mixture was filtered hot to give a pale filtrate which quickly became dark red. C8H12N2, fw=136.19. Yield 1.78 g, 98.7%. Mp: 60° C. (melt). 1H NMR (300 MHz, CDCl3): δ 6.54(s, 2H), 3.46 (br s, 2H), 3.21 (br s, 2H), 2.22 (s, 3H), 2.11 (s, 3H). Rf=0.68 (ethyl acetate/silica). The flask was fitted with a condenser was left to reflux After refluxing for 18 hours the mixture was filtered hot to give a pale filtrate which quickly became dark red

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

Procedure: To a 125 mL round bottom flask 2.20 g of 2,3-dimethyl-6-nitro-aniline (13.2 mmol) was added. Then 15 mL of ethanol was added to the flask followed by the addition of 4 mL of 20 wt % NaOH in water. Then 2.0 g of zinc dust was added to the flask. The flask was fitted with a condenser and was left to reflux with stirring. After about 0.5 hours the mixture became very pale-brown. After refluxing for 18 hours the mixture was filtered hot to give a pale filtrate which quickly became dark red. C8H12N2, fw=136.19. Yield 1.78 g, 98.7%. Mp: 60° C. (melt). 1H NMR (300 MHz, CDCl3): δ 6.54 (s, 2H), 3.46 (br s, 2H), 3.21 (br s, 2H), 2.22 (s, 3H), 2.11 (s, 3H). Rf=0.68 (ethyl acetate/silica). The flask was fitted with a condenser was left to reflux After refluxing for 18 hours the mixture was filtered hot to give a pale filtrate which quickly became dark red

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

Procedure: 2-(4-Nitrophenyl)-4,5-dimethyl benzimidazole was prepared by mixing 1,2-diamino-3,4-dimethylbenzene (1.36 g, 9.8 mmole with 4-nitrobenzoic acid (1.67 g, 9.8 mmole) and dissolved in POCl3 (10 ml) and heated to reflux for 2.5 hours. The reaction mixture was cooled and cautiously poured onto ice. The resulting solid was filtered, washed with NaHCO3 and used without further purification. heated to reflux for 2.5 hours The reaction mixture was cooled cautiously poured onto ice The resulting solid was filtered washed with NaHCO3 used without further purification

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

Procedure: 2-(4-Nitrophenyl)-4,5-dimethyl benzimidazole was prepared by mixing 1,2-diamino-3,4-dimethylbenzene (1.36 g, 9.8 mmole with 4-nitrobenzoic acid (1.67 g, 9.8 mmole) and dissolved in POCl3 (10 ml) and heated to reflux for 2.5 hours. The reaction mixture was cooled and cautiously poured onto ice. The resulting solid was filtered, washed with NaHCO3 and used without further purification. heated to reflux for 2.5 hours The reaction mixture was cooled cautiously poured onto ice The resulting solid was filtered washed with NaHCO3 used without further purification

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

Procedure: This compound was prepared by the method described in Example 1, using 3-methyl-4-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzaldehyde (180 mg, 0.65 mmol, 1.0 equiv), 3,4-dimethyl-benzene-1,2-diamine (89 mg, 0.65 mmol, 1.0 equiv), and Na2S2O5 (161 mg, 0.85 mmol, 1.3 equiv) in General Procedure 3. Purification by Method 2 afforded 192 mg (75%) of the title compound. MS (electrospray): mass calculated for C24H32N4O, 392.26; m/z found, 393.5 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.95-7.85 (m, 2H), 7.35-7.23 (m, 1H), 7.08-7.00 (m, 2H), 4.12 (t, J=6.0 Hz, 2H), 2.64-2.37 (m, 16H), 2.29 (s, 6H), 2.10-2.00 (m, 2H). This compound was prepared by the method Purification by Method 2

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

Procedure: This compound was prepared by the method described in Example 1, using 3-methyl-4-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzaldehyde (180 mg, 0.65 mmol, 1.0 equiv), 3,4-dimethyl-benzene-1,2-diamine (89 mg, 0.65 mmol, 1.0 equiv), and Na2S2O5 (161 mg, 0.85 mmol, 1.3 equiv) in General Procedure 3. Purification by Method 2 afforded 192 mg (75%) of the title compound. MS (electrospray): mass calculated for C24H32N4O, 392.26; m/z found, 393.5 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.95-7.85 (m, 2H), 7.35-7.23 (m, 1H), 7.08-7.00 (m, 2H), 4.12 (t, J=6.0 Hz, 2H), 2.64-2.37 (m, 16H), 2.29 (s, 6H), 2.10-2.00 (m, 2H). This compound was prepared by the method Purification by Method 2

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

Procedure: 2-{(2-Chloro-4-[3-(4-methyl-piperazin-1-yl)-propoxy]-phenyl}-4,5-dimethyl-1H-benzoimidazole. 2-Chloro-4-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzaldehyde (91.5 mg, 0.31 mmol, 1.0 equiv) and 3,4-dimethyl-benzene-1,2-diamine (42 mg, 0.31 mmol, 1.0 equiv) were stirred with Na2S2O5 (76 mg, 0.40 mmol, 1.3 equiv) in DMF (0.25 M) at 90° C. for 12 h. The reaction mixture was loaded directly on silica gel and purified according to Method 2, which afforded 98 mg (76%) of the title compound. MS (electrospray): mass calculated for C23H29ClN4O, 412.20; m/z found, 413.4 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.68 (br s, 1H), 7.33 (br s, 1H), 7.15 (d, J=2.5 Hz, 1H), 7.07 (d, J=8.7, 2.5 Hz, 1H), 7.03 (dd, J=8.7, 2.5 Hz, 1H), 4.13 (t, J=6.1 Hz, 2H), 2.60-2.39 (m, 13H), 2.39 (s, 3H), 2.30 (s, 3H), 2.05-1.95 (m, 2H). purified

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

Procedure: This compound was prepared by the method described in Example 1, using 3-methyl-4-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzaldehyde (180 mg, 0.65 mmol, 1.0 equiv), 3,4-dimethyl-benzene-1,2-diamine (89 mg, 0.65 mmol, 1.0 equiv), and Na2S2O5 (161 mg, 0.85 mmol, 1.3 equiv) in General Procedure 3. Purification by Method 2 afforded 192 mg (75%) of the title compound. MS (electrospray): mass calculated for C24H32N4O, 392.26. m/z found, 393.5 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.95-7.85 (m, 2H), 7.35-7.23 (m, 1H), 7.08-7.00 (m, 2H), 4.12 (t, J=6.0 Hz, 2H), 2.64-2.37 (m, 16H), 2.29 (s, 6H), 2.10-2.00 (m, 2H). This compound was prepared by the method Purification by Method 2