2,3-dihydro-1H-inden-2-ylmethanamine

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

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

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl chloroformate (3.3 ml, 34 mmol) is added to a cooled (0° C.) solution of indan-2-yl acetic acid (5.0 g, 28.4 mmol) and triethylamine (4.75 ml, 34 mmol) in acetone (40 ml) and water (8 ml). After 30 minutes, a solution of sodium azide (2.8 g, 42.6 mmol) in water (16 ml) is added and the reaction is stirred at 5° C. for 1 hour, prior to addition of brine and ice. The mixture is extracted with ether and the combined extracts are dried (Na2SO4) and evaporated. The resultant acyl azide is taken into toluene (50 ml) and heated at 100° C. until nitrogen evolution ceases. After evaporation of solvent, the resultant isocyanate is taken into 6N HCl (40 ml) and heated at 100° C. for 16 hours. The reaction mixture is evaporated to ⅓ volume and the resultant solid collected by filtration, washed with water and ether, then dried. The resultant hydrochloride salt is suspended in ether (20 ml) and ammonia is bubbled for 10 minutes. Water is added and the organic layer is separated, dried (Na2SO4) and evaporated to afford the title compound [MH+CH3CN]+189. The mixture is extracted with ether the combined extracts are dried (Na2SO4) evaporated heated at 100° C. until nitrogen evolution ceases After evaporation of solvent heated at 100° C. for 16 hours The reaction mixture is evaporated the resultant solid collected by filtration washed with water and ether dried ammonia is bubbled for 10 minutes Water is added the organic layer is separated dried (Na2SO4) evaporated

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

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

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl chloroformate (3.3 ml, 34 mmol) is added to a cooled (0° C.) solution of indan-2-yl acetic acid (5.0 g, 28.4 mmol) and triethylamine (4.75 ml, 34 mmol) in acetone (40 ml) and water (8 ml). After 30 minutes, a solution of sodium azide (2.8 g, 42.6 mmol) in water (16 ml) is added and the reaction is stirred at 5° C. for 1 hour, prior to addition of brine and ice. The mixture is extracted with ether and the combined extracts are dried (Na2SO4) and evaporated. The resultant acyl azide is taken into toluene (50 ml) and heated at 100° C. until nitrogen evolution ceases. After evaporation of solvent, the resultant isocyanate is taken into 6N HCl (40 ml) and heated at 100° C. for 16 hours. The reaction mixture is evaporated to ⅓ volume and the resultant solid collected by filtration, washed with water and ether, then dried. The resultant hydrochloride salt is suspended in ether (20 ml) and ammonia is bubbled for 10 minutes. Water is added and the organic layer is separated, dried (Na2SO4) and evaporated to afford the title compound [MH+CH3CN]+189. The mixture is extracted with ether the combined extracts are dried (Na2SO4) evaporated heated at 100° C. until nitrogen evolution ceases After evaporation of solvent heated at 100° C. for 16 hours The reaction mixture is evaporated the resultant solid collected by filtration washed with water and ether dried ammonia is bubbled for 10 minutes Water is added the organic layer is separated dried (Na2SO4) evaporated

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

Procedure: The following was added sequentially to DCM (8 mL): 1-(1-(4-chlorobenzyl)-1H-indole-2-carbonyl)piperidine-4-carboxylic acid (180 mg, 0.454 mmol), DIPEA (0.317 mL, 1.814 mmol), EDC (96 mg, 0.499 mmol), HOBT (76 mg, 0.499 mmol), and crude (2,3-dihydro-1H-inden-2-yl)methanamine (˜105 mg, 0.713 mmol). The mixture was stirred for 18 h at rt, at which time the solution diluted with a 1:1 solution of ethyl acetate:diethyl ether and washed with 1M HCl (1×), 10% aq. sodium carbonate (1×). The organic phase was dried with magnesium sulfate and concentrated in vacuo. Purification was accomplished via silica gel flash chromatography (60 g silica, 50% EtOAc/Hexanes), followed by EtOAc/hexane trituration to give the title compound as a white powder. (Yield: 137 mg, 0.260 mmol, 57%) 1H NMR (400 MHz, CDCl3) 7.66, 7.36-7.14, 7.04, 6.65, 5.55-5.40, 4.35, 3.39, 3.15-3.03, 2.88, 2.71-2.65, 2.31-2.19, 1.74, 1.49 diethyl ether and washed with 1M HCl (1×), 10% aq. sodium carbonate (1×) The organic phase was dried with magnesium sulfate concentrated in vacuo Purification

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

Procedure: 10.6 g (37.7 mmol) of 2-(benzyloxycarbonylaminomethyl)indan was dissolved in 100 ml of methanol, to which 1.3 g of palladium on carbon was added and stirred for 4 hours in the stream of hydrogen. The catalyst was removed by filtration, the solvent was evaporated, and 5.04 g of 2-(aminomethyl)indan was obtained. The obtained compound was immediately dissolved in 150 ml of methylene chloride, to which 100 ml of water and 6.2 g of potassium carbonate were added, and the mixture was vigorously stirred. 8.02 g (38.0 mmol) of 4-chlorobenzenesulfonyl chloride was added thereto portionwise under ice-cooling, followed by stirring for 30 minutes. The organic phase was collected, dried and the solvent was removed by distillation. The crystalline residue was recrystallized from a solvent mixture of ethyl acetate and hexane to obtain 9.82 g of 2-[(4-chlorophenyl)sulfonylaminomethyl]indan as colorless needles. Yield: 76% was added The catalyst was removed by filtration the solvent was evaporated

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

Procedure: Dissolved in 100 ml of methanol were 10.6 g (37.7 mmol) of 2-(benzyloxycarbonylaminomethyl)indane, and 1.3 g of 10% palladium-carbon were added to the solution. The mixture was stirred for 4 hours under a hydrogen atmosphere. After separating the catalyst by filtration, the solvent was distilled off to obtain 5.04 g of 2-(aminomethyl)indane. This compound was immediately dissolved in 150 ml of methylene chloride, and 100 ml of water and 6.2 g of potassium carbonate were added to the solution, followed by vigorous stirring of the resultant mixture. While chilling with ice water, 8.02 g (38.0 mmol) of 4-chlorobenzenesulfonyl chloride were added in small portions. Thereafter, the mixture was stirred for 30 minutes. After an organic layer separated was taken out and dried, the solvent was distilled out of the organic layer. The resultant crystalline residue was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain 9.82 g of 2-[(4-chlorophenyl)sulfonylaminomethyl]indane as a colorless needle crystal. Yield: 76%. were added to the solution After separating the catalyst by filtration the solvent was distilled off

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

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl chloroformate (3.3 ml, 34 mmol) is added to a cooled (0° C.) solution of indan-2-yl acetic acid (5.0 g, 28.4 mmol) and triethylamine (4.75 ml, 34 mmol) in acetone (40 ml) and water (8 ml). After 30 minutes, a solution of sodium azide (2.8 g, 42.6 mmol) in water (16 ml) is added and the reaction is stirred at 5° C. for 1 hour, prior to addition of brine and ice. The mixture is extracted with ether and the combined extracts are dried (Na2SO4) and evaporated. The resultant acyl azide is taken into toluene (50 ml) and heated at 100° C. until nitrogen evolution ceases. After evaporation of solvent, the resultant isocyanate is taken into 6N HCl (40 ml) and heated at 100° C. for 16 hours. The reaction mixture is evaporated to ⅓ volume and the resultant solid collected by filtration, washed with water and ether, then dried. The resultant hydrochloride salt is suspended in ether (20 ml) and ammonia is bubbled for 10 minutes. Water is added and the organic layer is separated, dried (Na2SO4) and evaporated to afford the title compound [MH+CH3CN]+189. The mixture is extracted with ether the combined extracts are dried (Na2SO4) evaporated heated at 100° C. until nitrogen evolution ceases After evaporation of solvent heated at 100° C. for 16 hours The reaction mixture is evaporated the resultant solid collected by filtration washed with water and ether dried ammonia is bubbled for 10 minutes Water is added the organic layer is separated dried (Na2SO4) evaporated