4-phenylbutan-1-amine

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

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

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

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

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

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

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

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

Procedure: 2-[5-(1,3-Dioxo-1,3-dihydroisoindol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-1H-benzoimidazole-5-carboxylic acid (0.05g, 0.111 mmol) was dissolved in anhydrous dimethylformamide (0.5 mL) and the solution was combined with 1-hydroxybenzotriazole hydrate (0.017 g, 0.126 mmol), benzotriazole-1-yloxytrispyrrolidinophosphoniurnhexafluoro-phosphate (0.063 g, 0.121 mmol) and N-methylmorpholine (0.013 mL, 0.118 mmol) at room temperature under an atomosphere of dry N2. After 2 minutes 4-phenylbutylamine (0.02 mL, 0.127 mmol) was added and the mixture was stirred at room temperature for 2 hours. The mixture was transferred to a sparatory funnel containing 20% ethanol/ethyl acetate solution (7 mL), 0.2N HCl (3.5 mL) and saturated aqueous NaCl (3.5 mL). The aqueous phase was extracted once with 20% ethanol/ethyl acetate solution (7 mL) and the combined organic phases were washed with a solution containing 0.2N HCl (3.5 mL) in saturated aqueous NaCl (3.5 mL) followed by a final washing with saturated aqueous sodium bicarbonate solution (7 mL). The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated to dryness on a rotary evaporator to provide 2-[5-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-N-(3-phenylpropyl)-1H-benzoimidazole-5-carboxamide as crude material (0.14 g). The mixture was transferred to a sparatory funnel The aqueous phase was extracted once with 20% ethanol/ethyl acetate solution (7 mL) the combined organic phases were washed with a solution containing 0.2N HCl (3.5 mL) in saturated aqueous NaCl (3.5 mL) a final washing with saturated aqueous sodium bicarbonate solution (7 mL) The organic phase was then dried over anhydrous sodium sulfate filtered concentrated to dryness on a rotary evaporator

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.50 g (1.2 mmole) of [(8R)-2-trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diaza-cyclopenta[a]naphthalen-8-yl]methyl 4-methylbenzenesulfonate and 0.75 g (5.0 mmole) of 4-phenylbutylamine in 25.0 mL of DMSO was heated at 80-90° C. under nitrogen for 4 hours. The reaction was allowed to come to room temperature, diluted to 500 mL with ethyl acetate, washed with 500 mL portions of saturated aqueous sodium bicarbonate and water, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel with 2% methanol in chloroform as eluant and the product fractions evaporated to give 0.24 g of the desired product. This was recrystallized from ethanol with the addition of oxalic acid to give 0.092 g of the (S)-enantiomer of the title compound as a white solid oxalate, hydrate, m.p. 124-127° C. to come to room temperature washed with 500 mL portions of saturated aqueous sodium bicarbonate and water dried over sodium sulfate filtered evaporated in vacuum chromatographed on silica gel with 2% methanol in chloroform as eluant the product fractions evaporated

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

Procedure: Using the procedures of Example 5, the title compound was prepared as a light yellow viscous oil (8.4 g, 65%) from 5.9 g (0.030 mole) of 3-phenoxybenzaldehyde (Fluka), 3.6 g (0.030 mole) of 2-mercapto-2-methylpropionic acid, and 4.6 g (0.030 mole) of 4-phenylbutylamine after refluxing in 250 ml of benzene overnight.

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

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

Procedure: A solution of 4-phenylbutylamine (610 μl, 3.86 mmol) and triethylamine (2.24 mL, 16.1 mmol) in 30 mL of methylene chloride was added under nitrogen dropwise to a solution of the carbonate prepared in Example 5 (2.0 g, 3.22 mmol) in 30 mL of methylene chloride at ice bath temperature. After the addition the cooling bath was removed and the reaction stirred at room temperature overnight. An additional 204 μl (1.29 mmol) of 4-phenylbutylamine and 180 μl (1.29 mmol) of triethylamine were added and the reaction stirred at room temperature for approximately 7 hours. The reaction was extracted one time with 1N HCl, multiple times with saturated Na2CO3, dried (MgSO4) and the solvent removed under reduced pressure to give 2.02 g of a crystalline solid. Purification of the solid on silica gel (230-400 mesh) using 5%-20% ethyl acetate-methylene chloride as the eluent gave 1.43 g (70%) of the title compounds as a white crystalline solid, mp 84°-86° C. After the addition the cooling bath was removed the reaction stirred at room temperature for approximately 7 hours The reaction was extracted one time with 1N HCl, multiple times with saturated Na2CO3 dried (MgSO4) the solvent removed under reduced pressure