2-methyl-1,3-dihydroisoindol-4-amine

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

実験手順: A 5-L flask was set up with an overhead stirrer, temperature probe, and 500-mL addition funnel. The flask was charged with lithium aluminum hydride (100 g) and anhydrous tetrahydrofuran (1.5 L). The resulting suspension was treated with 4-amino-2-methyl-1H-isoindole-1,3(2H)-dione (100 g, 0.56 mol) at a rate such that the reaction did not become too vigorous. The resulting suspension was heated at reflux for 18 hours. The reaction vessel was cooled, placed in an ice bath, and cautiously quenched with 100 mL water, 100 mL 1N NaOH, and 300 mL water. The resulting suspension was treated with chloroform (1.5 L) and the pH of the suspension adjusted to 12 with 50% aqueous sodium hydroxide solution. The resulting suspension was treated with acetic anhydride (300 mL) while maintaining the pH at approximately 12. The reaction mixture was treated with sodium sulfate (800 g) and potassium carbonate (200 g), and the reaction mixture was filtered. The filter cake was washed with additional chloroform, and the combined filtrates were concentrated. The residue was crystallized from ethyl acetate to give 71 g (66%) of the desired product, mp 157° C. A 5-L flask was set up with an overhead stirrer temperature probe, and 500-mL addition funnel The resulting suspension was heated at reflux for 18 hours The reaction vessel was cooled placed in an ice bath cautiously quenched with 100 mL water, 100 mL 1N NaOH, and 300 mL water The resulting suspension was treated with chloroform (1.5 L) The resulting suspension was treated with acetic anhydride (300 mL) while maintaining the pH at approximately 12 The reaction mixture was treated with sodium sulfate (800 g) and potassium carbonate (200 g) the reaction mixture was filtered The filter cake was washed with additional chloroform the combined filtrates were concentrated The residue was crystallized from ethyl acetate

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

実験手順: A 5-L flask was set up with an overhead stirrer, temperature probe, and 500-mL addition funnel. The flask was charged with lithium aluminum hydride (100 g) and anhydrous tetrahydrofuran (1.5 L). The resulting suspension was treated with 4-amino-2-methyl-1H-isoindole-1,3(2H)-dione (100 g, 0.56 mol) at a rate such that the reaction did not become too vigorous. The resulting suspension was heated at reflux for 18 hours. The reaction vessel was cooled, placed in an ice bath, and cautiously quenched with 100 mL water, 100 mL 1N NaOH, and 300 mL water. The resulting suspension was treated with chloroform (1.5 L) and the pH of the suspension adjusted to 12 with 50% aqueous sodium hydroxide solution. The resulting suspension was treated with acetic anhydride (300 mL) while maintaining the pH at approximately 12. The reaction mixture was treated with sodium sulfate (800 g) and potassium carbonate (200 g), and the reaction mixture was filtered. The filter cake was washed with additional chloroform, and the combined filtrates were concentrated. The residue was crystallized from ethyl acetate to give 71 g (66%) of the desired product, mp 157° C. A 5-L flask was set up with an overhead stirrer temperature probe, and 500-mL addition funnel The resulting suspension was heated at reflux for 18 hours The reaction vessel was cooled placed in an ice bath cautiously quenched with 100 mL water, 100 mL 1N NaOH, and 300 mL water The resulting suspension was treated with chloroform (1.5 L) The resulting suspension was treated with acetic anhydride (300 mL) while maintaining the pH at approximately 12 The reaction mixture was treated with sodium sulfate (800 g) and potassium carbonate (200 g) the reaction mixture was filtered The filter cake was washed with additional chloroform the combined filtrates were concentrated The residue was crystallized from ethyl acetate

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

実験手順: A solution of freshly prepared 4-amino-2,3-dihydro-2-methyl-1H-isoindole (400 mg, 3.0 mmol) in dry ethyl acethate (40 ml) under argon was treated dropwise with a solution of 5-chloro-2,4-dimethoxybenzoyl chloride (700 mg, 3.0 mmol) in a mixture of ethyl acethate (10 ml) and dichloromethane (10 ml). The reaction was stirred at room temperature for 6h and then concentrated in vacuo. The residue was triturated with diethyl ether/ethyl acethate and then crystallised twice from methanol/diethyl ether to give the title compound as a pale grey solid (0.11 g). concentrated in vacuo The residue was triturated with diethyl ether/ethyl acethate crystallised twice from methanol/diethyl ether

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

実験手順: A solution of 3-nitro-N-methylphthalimide (0.58 g, 2.8 mmol) in dry tetrahydrofuran (10 ml) was added dropwise to a stirred suspension of lithium aluminium hydride (0.64 g, 16.8 mmol) under argon. The mixture was stirred at room temperature for 2h and then heated under gentle reflux for 2.5h. The reaction was quenched by addition of wet diethyl ether followed by a minimum amount of water. The precipithated aluminium salts were removed by filtration. The filtrate was concentrated in vacuo to give the title compound as a brown oil (400 mg) which was used directly in the next stage (Example 31). heated under gentle reflux for 2.5h The reaction was quenched by addition of wet diethyl ether The precipithated aluminium salts were removed by filtration The filtrate was concentrated in vacuo

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

実験手順: A 5-L flask was set up with an overhead stirrer, temperature probe, and 500-mL addition funnel. The flask was charged with lithium aluminum hydride (100 g) and anhydrous tetrahydrofuran (1.5 L). The resulting suspension was treated with 4-amino-2-methyl-1H-isoindole-1,3(2H)-dione (100 g, 0.56 mol) at a rate such that the reaction did not become too vigorous. The resulting suspension was heated at reflux for 18 hours. The reaction vessel was cooled, placed in an ice bath, and cautiously quenched with 100 mL water, 100 mL 1N NaOH, and 300 mL water. The resulting suspension was treated with chloroform (1.5 L) and the pH of the suspension adjusted to 12 with 50% aqueous sodium hydroxide solution. The resulting suspension was treated with acetic anhydride (300 mL) while maintaining the pH at approximately 12. The reaction mixture was treated with sodium sulfate (800 g) and potassium carbonate (200 g), and the reaction mixture was filtered. The filter cake was washed with additional chloroform, and the combined filtrates were concentrated. The residue was crystallized from ethyl acetate to give 71 g (66%) of the desired product, mp 157° C. A 5-L flask was set up with an overhead stirrer temperature probe, and 500-mL addition funnel The resulting suspension was heated at reflux for 18 hours The reaction vessel was cooled placed in an ice bath cautiously quenched with 100 mL water, 100 mL 1N NaOH, and 300 mL water The resulting suspension was treated with chloroform (1.5 L) The resulting suspension was treated with acetic anhydride (300 mL) while maintaining the pH at approximately 12 The reaction mixture was treated with sodium sulfate (800 g) and potassium carbonate (200 g) the reaction mixture was filtered The filter cake was washed with additional chloroform the combined filtrates were concentrated The residue was crystallized from ethyl acetate