ethyl 2-(1H-indol-3-yl)-2-oxoacetate

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

Procedure: Pyridine (40 mL, 492 mmol) was added in a single portion to a chilled solution (0° C.) of indole (48 g, 410 mmol) in diethyl ether (820 mL). Ethyl chlorooxoacetate (50 mL, 451 mmol) was added dropwise. The resulting suspension was allowed to warm to ambient temperature over a period of 20 hours. The solid was isolated by filtration and washed with diethyl ether. The solid was combined with water (1 L), stirred for 1 hour, and then isolated by filtration to provide 75 g of ethyl (1H-indol-3-yl)(oxo)acetate. The solid was isolated by filtration washed with diethyl ether isolated by filtration

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

Procedure: Pyridine (40 mL, 492 mmol) was added in a single portion to a chilled solution (0° C.) of indole (48 g, 410 mmol) in diethyl ether (820 mL). Ethyl chlorooxoacetate (50 mL, 451 mmol) was added dropwise. The resulting suspension was allowed to warm to ambient temperature over a period of 20 hours. The solid was isolated by filtration and washed with diethyl ether. The solid was combined with water (1 L), stirred for 1 hour, and then isolated by filtration to provide 75 g of ethyl (1H-indol-3-yl)(oxo)acetate. The solid was isolated by filtration washed with diethyl ether isolated by filtration

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

Procedure: Pyridine (40 mL, 492 mmol) was added in a single portion to a chilled solution (0° C.) solution of indole (48 g, 410 mmol) in diethyl ether (820 mL). Ethyl chlorooxoacetate (50 mL, 451 mmol) was added dropwise. The resulting suspension was allowed to warm to ambient temperature over a period of 20 hours. The solid was isolated by filtration and washed with diethyl ether. The solid was combined with water (1 L), stirred for 1 hour, and then isolated by filtration to provide 75 g of ethyl (1H-indol-3-yl)(oxo)acetate. The solid was isolated by filtration washed with diethyl ether isolated by filtration

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

Procedure: Pyridine (40 mL, 492 mmol) was added in a single portion to a chilled solution (0° C.) solution of indole (48 g, 410 mmol) in diethyl ether (820 mL). Ethyl chlorooxoacetate (50 mL, 451 mmol) was added dropwise. The resulting suspension was allowed to warm to ambient temperature over a period of 20 hours. The solid was isolated by filtration and washed with diethyl ether. The solid was combined with water (1 L), stirred for 1 hour, and then isolated by filtration to provide 75 g of ethyl (1H-indol-3-yl)(oxo)acetate. The solid was isolated by filtration washed with diethyl ether isolated by filtration

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

Procedure: The general procedure 1 was then followed using 1-(3-chloropropyl)-4-methylpiperazine (12.5 mmol, 2.2 g), ethyl-2-(1H-indol-3-yl)-2-oxoacetate (10 mmol, 2.17 g) and K2CO3 (10.8 mmol, 1.5 g). The purification was achieved by column chromatography (petrolether:ethylacetate:diethylamine 5:5:1) to yield ethyl-2-{1-[3-(4-methylpiperazin-1-yl)propyl]-1H-indol-3-yl}-2-oxoacetate (5.3 mmol, 42%). IR {tilde over (ν)} [cm−1]=2936; 2790; 1727; 1638. FD-MS m/z (rel. int.)=359.9 (2.05%; M+•). 1H NMR (300 MHz, CDCl3) 8.40 (m; 2H; indole-H); 7.36 (m; 3H; indole-H); 4.38 (q; 3J=7.1 Hz; 2H; OCH2CH3); 4.25 (t; 3J=6.5 Hz; 2H; indole-CH2CH2CH2N); 2.44 (m; 8H; 4′piperazin-CH2); 2.30 (s; 3H; CH3); 2.26 (t; 3J=6.5 Hz; 2H; indole-CH2CH2CH2N); 2.00 (m; 2H; The purification

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

Procedure: The general procedure 1 was then followed using 1-(2-chloroethyl)piperidine (10 mmol, 1.5 g), ethyl-2-(1H-indol-3-yl)-2-oxoacetate (7 mmol, 1.5 g) and K2CO3 (10.9 mmol, 1.5 g). The purification was achieved by column chromatography (petrol-ether:ethylacetate:diethylamine 8:1:1) to yield ethyl-2-{1-[2-(piperidin-1-yl)ethyl]-1H-indol-3-yl}2-oxoacetate (4.6 mmol, 66%) as an pale yellow oil. IR {tilde over (ν)} [cm−1]=2936; 2857; 1730; 1638. EI-MS m/z (rel. int.)=328 (18.99%; M+•). 1H NMR (300 MHz, CDCl3) 8.43 (m; 2H; indole-H); 7.35 (m; 3H; indole-H); 4.40 (q; 3J=7.1 Hz; 2H; OCH2CH3); 4.25 (t; 3J=6.8 Hz; 2H; indole-CH2CH2N); 2.72 (t; 3J=6.8 Hz; 2H; indole-CH2CH2N); 2.43 (m; 4H; piperidin-CH2 (C-2+6)); 1.57 (m; 4H; piperidin-CH2 (C-3+5)); 1.43 (m; 5H; piperidin-CH2 (C-4)+OCH2CH3). The purification

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

Procedure: The general procedure 1 was then followed using 1-chloro-3-dimethylaminopropane (7 mmol, 0.75 g), ethyl-2-(1H-indol-3-yl)-2-oxoacetate (6 mmol, 1.3 g) and Cs2CO3 (6.6 mmol, 2.15 g). The purification was achieved by column chromatography (petrolether:ethylacetate:diethylamine 6:3:1) to yield ethyl-2-{1-[2-(dimethylamino)ethyl]-1H-indol-3-yl}-2-oxoacetate (3.8 mmol, 63%) as an pale yellow oil. IR {tilde over (ν)} [cm−1]=3023; 2962; 2917; 1732; 1630. EI-MS m/z (rel. int.)=302 (8.21%; M+•). 1H NMR (300 MHz, CDCl3) 8.43 (m; 1H; indole-H); 8.39 (s; 1H; indole-H); 7.33 (m; 3H; indole-H); 4.40 (q; 3J=7.1 Hz; 2H; OCH2CH3); 4.27 (t; 3J=6.8 Hz; 2H; indole-CH2CH2CH2N); 2.22 (s; 6H; N(CH3)2); 2.20 (m; 2H; indole-CH2CH2CH2N); 2.00 (quint; 3J=6.7 Hz; 2H; indole-CH2CH2CH2N); 1.42 (t; 3J=7.1 Hz; 3HOCH2CH3). The purification

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

Procedure: The general procedure 1 was then followed using 1-chloro-2-dimethylaminoethane (6 mmol, 0.65 g), ethyl-2-(1H-indol-3-yl)-2-oxoacetate (6 mmol, 1.3 g) and Cs2CO3 (6.6 mmol, 2.15 g). The purification was achieved by column chromatography (petrolether:ethylacetate:diethylamine 6:3:1) to yield ethyl-2-{1-[2-(dimethylamino)-ethyl]-1H-indol-3-yl}-2-oxoacetate (3.7 mmol, 62%) as pale yellow crystals. Mp=71-72° C. IR {tilde over (ν)} [cm−1]=3139; 3044; 2977; 2946; 2797; 2772; 1727; 1641. EI-MS m/z (rel. int.)=288 (19.15%; M+•). 1H NMR (300 MHz, CDCl3) 8.45 (m; 2H; indole-H); 7.37 (m; 3H; indole-H); 4.41 (q; 3J=7.1 Hz; 2H; OCH2CH3); 4.26 (t; 3J=6.9 Hz; 2H; indole-CH2CH2N); 2.76 (t; 3J=6.9 Hz; 2H; indole-CH2CH2N); 2.31 (s; 6H); 1.44 (t; 3H; 3J=7.1 Hz; OCH2CH3). The purification

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

Procedure: The general procedure 1 was then followed using the above product (7.14 mmol, 1.7 g), ethyl-2-(1H-indol-3-yl)-2-oxoacetate (4.6 mmol, 1.0 g) and Cs2CO3 (9.21 mmol, 3.0 g). The purification was achieved by column chromatography (petrol-ether:ethylacetate 1:1) to yield ethyl-2-(1-{3-[(tert.-butoxycarbonyl)amino]propyl}-1H-indol-3-yl)-2-oxoacetate (5.3 mmol, 74%) as pale yellow crystals. Mp 89-90° C. IR {tilde over (ν)} [cm−1]=3392; 2977; 2936; 1727; 1698; 1619; 1515. EI-MS m/z (rel. int.)=374 (8.9%; M+•). 1H NMR (300 MHz, CDCl3) 8.45 (m; 2H; indole-H); 7.35 (m; 3H; indole-H); 4.63 (bs; 1H; NH); 4.41 (q; 3J=7.1 Hz; 2H; OCH2CH3); 4.24 (t; 3J=7.1 Hz; 2H; indole-CH2); 3.18 (q; 3J=6.1 Hz; 2H; CH2N); 2.09 (m; 2H; CH2CH2CH2); 1.44 (s; 9H; C(CH3)3); 1.43 (t; 3J=7.1 Hz; 3H; OCH2CH3). The purification

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

Procedure: The general procedure 1 was then followed using the above product (6.68 mmol, 1.54 g), ethyl-2-(1H-indol-3-yl)-2-oxoacetate (6.68 mmol, 1.45 g) and Cs2CO3 (9.82 mmol, 3.20 g). The purification was achieved by column chromatography (petrol-ether:ethylacetate:diethylamine 5:4:1) to yield ethyl-2-(1-{2-[(tert.-butoxycarbonyl)-amino]ethyl}-1H-indol-3-yl)-2-oxoacetate (4.54 mmol, 68%) as white crystals. Mp=114-115° C. IR {tilde over (ν)} [cm−1]=3357; 2977; 1727; 1686; 1638; 1518. EI-MS (m/z)=360 (7.59%; M+•). 1H NMR (300 MHz, CDCl3) 8.44 (m; 1H; indole-H); 8.34 (s; 1H; indole-H); 7.42 (m; 1H; indole-H); 7.35 (m; 1H; indole-H); 4.63 (bs; 1H; NH); 4.37 (m; 4H; OCH2CH3; indole-CH2); 3.54 (q; 3J=6.2 Hz; 2H; CH2—N); 1.43 (t; 3H; 3J=7.1 Hz; OCH2CH3); 1.43 (s; 9H; C(CH3)3). The purification

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

Procedure: Pyridine (40 mL, 492 mmol) was added in a single portion to a chilled solution (0° C.) solution of indole (48 g, 410 mmol) in diethyl ether (820 mL). Ethyl chlorooxoacetate (50 mL, 451 mmol) was added dropwise. The resulting suspension was allowed to warm to ambient temperature over a period of 20 hours. The solid was isolated by filtration and washed with diethyl ether. The solid was combined with water (1 L), stirred for 1 hour, and then isolated by filtration to provide 75 g of ethyl (1H-indol-3-yl)(oxo)acetate. The solid was isolated by filtration washed with diethyl ether isolated by filtration

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

Procedure: The general procedure 1 was then followed using 1-(3-chloropropyl)-4-methylpiperazine (12.5 mmol, 2.2 g), ethyl-2-(1H-indol-3-yl)-2-oxoacetate (10 mmol, 2.17 g) and K2CO3 (10.8 mmol, 1.5 g). The purification was achieved by column chromatography (petro-lether:ethylacetate:diethylamine 5:5:1) to yield ethyl-2-{1-[3-(4-methylpiperazin-1-yl)propyl]-1H-indol-3-yl}-2-oxoacetate (5.3 mmol, 42%). IR [cm−1]=2936; 2790; 1727; 1638. FD-MS m/z (rel. int.)=359.9 (2.05%; M+•.). 1H NMR (300 MHz, CDCl3) 8.40 (m; 2H; indole-H); 7.36 (m; 3H; indole-H); 4.38 (q; 3J=7.1 Hz; 2H; OCH2CH3); 4.25 (t; 3J=6.5 Hz; 2H; indole-CH2CH2CH2N); 2.44 (m; 8H; 4× piperazin-CH2); 2.30 (s; 3H; CH3); 2.26 (t; 3J=6.5 Hz; 2H; indole-CH2CH2CH2N); 2.00 (m; 2H; The purification