2-(1H-indol-2-yl)ethanamine

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

Procedure: To a suspension of 1,2-difluoro-4-nitrobenzene (1.59 g, 10 mmol) and K2CO3 (6.90 g, 50 mmol) in DCM (40 mL) was added 2-(1H-indol-2-yl)ethanamine (1.96 g, 10 mmol) in one portion under N2 and the mixture was stirred at rt for 24 h. The mixture was then filtered, and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1) to give the title compound as a yellow solid (2.32 g, 78%). The mixture was then filtered the filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1)

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

Procedure: To a suspension of 1,2-difluoro-4-nitrobenzene (1.59 g, 10 mmol) and K2CO3 (6.90 g, 50 mmol) in DCM (40 mL) was added 2-(1H-indol-2-yl)ethanamine (1.96 g, 10 mmol) in one portion under N2 and the mixture was stirred at rt for 24 h. The mixture was then filtered, and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1) to give the title compound as a yellow solid (2.32 g, 78%). The mixture was then filtered the filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1)

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

Procedure: To a suspension of 1,2-difluoro-4-nitrobenzene (1.59 g, 10 mmol) and K2CO3 (6.90 g, 50 mmol) in DCM (40 mL) was added 2-(1H-indol-2-yl)ethanamine (1.96 g, 10 mmol) in one portion under N2 and the mixture was stirred at rt for 24 h. The mixture was then filtered, and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1) to give the title compound as a yellow solid (2.32 g, 78%). The mixture was then filtered the filtrate was concentrated in vacuo The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1)

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

Procedure: To a solution of 2-(indol-2-yl)ethylamine (2.7 g) in acetic acid (25 ml) at 15° C. wa added sodium cyanoborohydride (2.22 g) in one portion. The solution was stirred at room temperature for 15 hours and diluted with chilled water. The mixture was made basic with sodium hydroxide pellets and extracted three times with ether. The ether layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo to give 2-(2,3-dihydroindol-2-yl)ethylamine (1.41 g) as an oil. The oil was dissolved in tetrahydrofuran (50 ml) and treated with 1,1'-carbonyldiimidazole (1.13 g) at room temperature. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (30%-ethyl acetate-chloroform) to give crystals. The crystals were washed with ether to give 3,4,4a,5-tetrahydropyrimido[1,6-a]indol-1(2H)-one (0.74 g). extracted three times with ether The ether layer was washed with brine dried over anhydrous magnesium sulfate evaporated in vacuo

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

Procedure: To a solution of 2-(indol-2-yl)ethylamine (2.7 g) in acetic acid (25 ml) at 15° C. was added sodium cyanoborohydride (2.22 g) in one portion. The solution was stirred at room temperature for 15 hours and diluted with chilled water. The mixture was made basic with sodium hydroxide pellets and extracted three times with ether. The ether layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo to give 2-(2,3-dihydroindol-2-yl)ethylamine (1.41 g) as an oil. The oil was dissolved in tetrahydrofuran (50 ml) and treated with 1,1'-carboxyldiimidazole (1.13 g) at room temperature. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (30%-ethyl acetate-chloroform) to give crystals. The crystals were washed with ether to give 3,4,4a,5-tetrahydropyrimido[1,6-a]indol-1(2H)-one (0.74 g). extracted three times with ether The ether layer was washed with brine dried over anhydrous magnesium sulfate evaporated in vacuo

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

Procedure: A process disclosed in U.S. patent application Ser. No. 10/302,636 for making 4-{3-[1-benzhydryl-5-chloro-2-(2-{[3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid may be summarized as follows: methyl-4-iodobenzoate is reacted with allyl alcohol to provide 4-(3-Oxo-propyl)-benzoic acid methyl ester, which is then reacted with 5-chloro-2-methylindole to yield 4-[3-(5-chloro-2-methylindol-3-yl)propyl]benzoic acid methyl ester; this product is reacted with benzhydryl bromide to produce 4-[3-(1-benzhydryl-5-chloro-2-methylindol-3-yl)propyl]benzoic acid methyl ester, which is then reacted with benzoyl peroxide to produce the 2-formyl indole; the 2 formyl indole is then reacted with nitromethane followed by Zn(Hg)/HCl to form the 2-(2-aminoethyl) indole; this amine is then reacted with [(3,4-dichlorophenyl)-methyl]sulfonyl chloride to produce 4-{3-[1-benzhydryl-5-chloro-2-(2-{[3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid methyl ester, which is then hydrolyzed to form 4-{3-[1-benzhydryl-5-chloro-2-(2-{[3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid. In this process, chromatography is used to separate some of the compounds made in the aforesaid reactions. It would be desirable to have a process for making the product that does not require the use of chromatography.