3,3,3-trifluoro-2,2-dimethylpropanimidamide;hydrochloride

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1. The reaction mixture is cooled the aqueous layer is extracted 4-times with 10% methanol in dichloromethane The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1. The reaction mixture is cooled the aqueous layer is extracted 4-times with 10% methanol in dichloromethane The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1. The reaction mixture is cooled the aqueous layer is extracted 4-times with 10% methanol in dichloromethane The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1. The reaction mixture is cooled the aqueous layer is extracted 4-times with 10% methanol in dichloromethane The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3,3,3-Trifluoro-2,2-dimethyl-propionitrile (Stage 44.3) (12.40 mmol) was added to a solution of sodium methoxide (freshly prepared from 48.40 mmol sodium metal and 102 mL MeOH) at rt. After 4 h, acetic acid (48.40 mmol) and then NH4Cl (14.88 mmol) were slowly added and the reaction mixture was then heated to 70° C. for 40 h. After concentrating (40° C., 100 mbar) the reaction mixture, the residue was suspended in acetone, filtered and dried under vacuum to afford the title compound as a white solid. ESI-MS: [M+H]+ 155. After concentrating (40° C., 100 mbar) the reaction mixture filtered dried under vacuum

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

実験手順: The title compound was prepared in analogy to the procedure described for Intermediate A but in Stage A.3 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (Stage 44.2) was used instead of tert-butylamidine hydrochloride.

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1. The reaction mixture is cooled the aqueous layer is extracted 4-times with 10% methanol in dichloromethane The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Powdered sodium hydroxide (0.42 g) is added to a solution of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (0.93 g, prepared as described by S. Wang et al J. Med. Chem. 2004, 47, 1662-1675.) and 3,3,3-trifluoro-2,2-dimethyl-propionamidine hydrochloride (0.54 g) in 2-methoxyethanol (7 ml) and the mixture is heated at 125° C. for 1 hour with stirring. The reaction mixture is cooled, water is added, and the aqueous layer is extracted 4-times with 10% methanol in dichloromethane. The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration. HPLC/MS: retention time 1.47 minutes, M+H 303.1. The reaction mixture is cooled the aqueous layer is extracted 4-times with 10% methanol in dichloromethane The combined organic layers are purified by reversed phase chromatography and sodium bicarbonate is added to the fractions containing the title compound to give a white precipitate, which is collected by filtration