4-amino-2-chloro-N,N-dimethylbenzamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Amino-2-chloro-N,N-dimethylbenzamide (1.0 g) and triethylamine (1.21 g) were dissolved in methylene chloride (20 ml) and the solution was cooled to 0°-5° C. 2,2-Dimethylpropionyl chloride (1.21 g) was added dropwise keeping the temperature below 10° C. and the resulting orange solution stirred at 0°-10° C. for 0.5 hour. The organic solution was then washed with aqueous sodium bicarbonate and then water, dried and evaporated to give an orange solid. This was recrystallised from 3:1 ethyl acetate:chloroform to give 2-chloro-(2',2'-dimethylpropionamido)-N,N-dimethylbenzamide as an off-white crystalline solid (1.027 g), m.p. 202°-203° C. the solution was cooled to 0°-5° C the temperature below 10° C. The organic solution was then washed with aqueous sodium bicarbonate water, dried evaporated to give an orange solid This was recrystallised from 3:1 ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Iron powder (pre-reduced with hydrogen, 10.0 g) was suspended in ethanol (80 ml) and water (10 ml) and concentrated hydrochloric acid (4 ml) were added with vigorous stirring. 2-Chloro-4-nitro-N,N-dimethylbenzamide (7.50 g) was added in small portions over 15 minutes and the mixture then heated to 50°-60° C. and stirred for 5 hours. The mixture was filtered through Celite and the ethanol evaporated. Water (200 ml) and concentrated hydrochloric acid (20 ml) were added and the reaction washed with ethyl acetate and then basified to pH8 with sodium bicarbonate and extracted with methylene chloride. The organic extract was dried and evaporated to give 4-amino-2-chloro-N,N-dimethylbenzamide as a grey crystalline solid (5.21 g) which was recrystallised from chloroform/ethyl acetate to give off-white crystals (3.46 g, m.p. 170°-173° C.). the mixture then heated to 50°-60° C. The mixture was filtered through Celite the ethanol evaporated Water (200 ml) and concentrated hydrochloric acid (20 ml) were added the reaction washed with ethyl acetate extracted with methylene chloride The organic extract was dried evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Amino-2-chloro-N,N-dimethylbenzamide (1.0 g) and triethylamine (1.21 g) were dissolved in methylene chloride (20 ml) and the solution was cooled to 0°-5° C. 2,2-Dimethylpropionyl chloride (1.21 g) was added dropwise keeping the temperature below 10° C. and the resulting orange solution stirred at 0°-10° C. for 0.5 hour. The organic solution was then washed with aqueous sodium bicarbonate and then water, dried and evaporated to give an orange solid. This was recrystallised from 3:1 ethyl acetate:chloroform to give 2-chloro-(2',2'-dimethylpropionamido)-N,N-dimethylbenzamide as an off-white crystalline solid (1.027 g), m.p. 202°-203° C. the solution was cooled to 0°-5° C the temperature below 10° C. The organic solution was then washed with aqueous sodium bicarbonate water, dried evaporated to give an orange solid This was recrystallised from 3:1 ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Iron powder (pre-reduced with hydrogen, 10.0 g) was suspended in ethanol (80 ml) and water (10 ml) and concentrated hydrochloric acid (4 ml) were added with vigorous stirring. 2-Chloro-4-nitro-N,N-dimethylbenzamide (7.50 g) was added in small portions over 15 minutes and the mixture then heated to 50°-60° C. and stirred for 5 hours. The mixture was filtered through Celite and the ethanol evaporated. Water (200 ml) and concentrated hydrochloric acid (20 ml) were added and the reaction washed with ethyl acetate and then basified to pH8 with sodium bicarbonate and extracted with methylene chloride. The organic extract was dried and evaporated to give 4-amino-2-chloro-N,N-dimethylbenzamide as a grey crystalline solid (5.21 g) which was recrystallised from chloroform/ethyl acetate to give off-white crystals (3.46 g, m.p. 170°-173° C.). the mixture then heated to 50°-60° C. The mixture was filtered through Celite the ethanol evaporated Water (200 ml) and concentrated hydrochloric acid (20 ml) were added the reaction washed with ethyl acetate extracted with methylene chloride The organic extract was dried evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Iron powder (pre-reduced with hydrogen, 10.0 g) was suspended in ethanol (80 ml) and water (10 ml) and concentrated hydrochloric acid (4 ml) were added with vigorous stirring. 2-Chloro-4-nitro-N,N-dimethylbenzamide (7.50 g) was added in small portions over 15 minutes and the mixture then heated to 50°-60° C. and stirred for 5 hours. The mixture was filtered through Celite and the ethanol evaporated. Water (200 ml) and concentrated hydrochloric acid (20 ml) were added and the reaction washed with ethyl acetate and then basified to pH8 with sodium bicarbonate and extracted with methylene chloride. The organic extract was dried and evaporated to give 4-amino-2-chloro-N,N-dimethylbenzamide as a grey crystalline solid (5.21 g) which was recrystallised from chloroform/ethyl acetate to give off-white crystals (3.46 g, m.p. 170°-173° C.). the mixture then heated to 50°-60° C. The mixture was filtered through Celite the ethanol evaporated Water (200 ml) and concentrated hydrochloric acid (20 ml) were added the reaction washed with ethyl acetate extracted with methylene chloride The organic extract was dried evaporated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using the procedure of Example 1, Compound 13a2 was used in place of Compound 1j3 and carried forward to prepare 4-amino-2-chloro-N,N-dimethyl-benzamide Compound 13a3. 1M LAH (3.53 mL, 3.53 mmol) was added dropwise to a solution of Compound 13a3 (700 mg, 3.53 mmol) in THF (10 mL). After 10 minutes, the reaction was cooled to 0° C. and quenched with water. The mixture was extracted from ethyl ether with 1N HCl. The aqueous layer was adjusted to pH 10 with NaOH and the product was extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated to give 3-chloro-4-dimethylaminomethyl-phenylamine Compound 13a (150 mg) as a viscous brown oil. MS 185 (MH+). quenched with water The mixture was extracted from ethyl ether with 1N HCl the product was extracted with EtOAc The combined organic layers were dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Chloro-2,2-dimethylpropionyl chloride (1.86 g) was added dropwise over 5 minutes to 4-amino-2-chloro-N,N-dimethylbenzamide (2.00 g) suspended in dry methylene chloride (40 ml) and dry triethylamine (1.21 g) with stirring, keeping the temperature below 10° C. After stirring for 1 hour and warming to room temperature, methylene chloride (40 ml) was added and the solution washed with 2M hydrochloric acid, saturated aqueous sodium bicarbonate and then saturated brine. The solution was then dried and evaporated to yield a sticky yellow solid which was recrystallised from ethyl acetate/chloroform to give 2-chloro-4-(3'-chloro-2',2'-dimethylpropionamido)-N,N-dimethylbenzamide, as a white crystalline solid (2.349 g) m.p. 179°-181° C. the temperature below 10° C the solution washed with 2M hydrochloric acid, saturated aqueous sodium bicarbonate The solution was then dried evaporated to yield a sticky yellow solid which was recrystallised from ethyl acetate/chloroform