ethyl 6-bromo-1H-indole-2-carboxylate

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 6-bromoindole-2-carboxylate (4.4 g, 16.4 mmol) in DMF (20 mL) was added dropwise over ˜2-3 min to a stirred suspension of sodium hydride (60%, 1.0 g, 25 mmol) in DMF (20 mL) at 0° C. under Ar. The reaction was stirred at 0° C. for 45 min then chloroacetonitrile (2.1 mL, 33 mmol) was added in one portion. The reaction was then heated to 75° C. and stirred for 1 h. After allowing to cool to room temperature the mixture was poured into water (150 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with brine (75 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate) to give the product as a yellow solid (4.8 g, 95%). IR νmax (Nujol)/cm−1 3320, 3089, 2925, 2855, 1898, 1705, 1609, 1530, 1521, 1470, 1449, 1427, 1400, 1394, 1377, 1367, 1336, 1308, 1265, 1205, 1151, 1134,1108, 1054, 1027, 993, 950, 90, 873, 841, 832, 802, 792, 762, 736, 663, 615 and 589; NMR OH (400 MHz; CDCl3) 7.61 (1H, s), 7.57 (1H, d, J.8.5 Hz), 7.37 (1H, d, J 1.5 Hz), 7.35 (1H, dd, J 8.5 Hz, 1.5 Hz), 5.57 (2H, s), 4.45 (2H, q, J 7.2 Hz), 1.42 (3H, t, J 7.2 Hz). The reaction was then heated to 75° C. stirred for 1 h to cool to room temperature the mixture extracted with ethyl acetate (3×75 mL) The combined organic extracts were washed with brine (75 mL) dried (magnesium sulfate) filtered the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 6-bromoindole-2-carboxylate (4.4 g, 16.4 mmol) in DMF (20 mL) was added dropwise over ˜2–3 min to a stirred suspension of sodium hydride (60%, 1.0 g, 25 mmol) in DM (20 mL) at 0° C. under Ar. The reaction was stirred at 0° C. for 45 min then chloroacetonitrile (2.1 mL, 33 mmol) was added in one portion. The reaction was then heated to 75° C. and stirred for 1 h. After allowing to cool to room temp the mixture was poured into water (150 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with brine (75 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate) to give the product as a yellow solid (4.8 g, 95%). IR νmax (Nujol)/cm−1 3320, 3089, 2925, 2855, 1898, 1705, 1609, 1530, 1521, 1470, 1449, 1427, 1400, 1394, 1377, 1367, 1336, 1308, 1265, 1205, 1151, 1134, 1108, 1054, 1027, 993, 950, 90, 873, 841, 832, 802, 792, 762, 736, 663, 615 and 589; NMR δH (400 MHz; CDCl3) 7.61 (1H, s), 7.57 (1H, d, J 8.5 Hz), 7.37 (1H, d, J 1.5 Hz), 7.35 (1H, dd, J 8.5 Hz, 1.5 Hz), 5.57 (2H, s), 4.45 (2H, q, J 7.2 Hz), 1.42 (3H, t, J 7.2 Hz). The reaction was then heated to 75° C. stirred for 1 h to cool to room temp the mixture extracted with ethyl acetate (3×75 mL) The combined organic extracts were washed with brine (75 mL) dried (magnesium sulfate) filtered the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 6-bromoindole-2-carboxylate (4.4 g, 16.4 mmol) in DMF (20 mL) was added dropwise over ˜2–3 min to a stirred suspension of sodium hydride (60%, 1.0 g, 25 mmol) in DM (20 mL) at 0° C. under Ar. The reaction was stirred at 0° C. for 45 min then chloroacetonitrile (2.1 mL, 33 mmol) was added in one portion. The reaction was then heated to 75° C. and stirred for 1 h. After allowing to cool to room temp the mixture was poured into water (150 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with brine (75 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate) to give the product as a yellow solid (4.8 g, 95%). IR νmax (Nujol)/cm−1 3320, 3089, 2925, 2855, 1898, 1705, 1609, 1530, 1521, 1470, 1449, 1427, 1400, 1394, 1377, 1367, 1336, 1308, 1265, 1205, 1151, 1134, 1108, 1054, 1027, 993, 950, 90, 873, 841, 832, 802, 792, 762, 736, 663, 615 and 589; NMR δH (400 MHz; CDCl3) 7.61 (1H, s), 7.57 (1H, d, J 8.5 Hz), 7.37 (1H, d, J 1.5 Hz), 7.35 (1H, dd, J 8.5 Hz, 1.5 Hz), 5.57 (2H, s), 4.45 (2H, q, J 7.2 Hz), 1.42 (3H, t, J 7.2 Hz). The reaction was then heated to 75° C. stirred for 1 h to cool to room temp the mixture extracted with ethyl acetate (3×75 mL) The combined organic extracts were washed with brine (75 mL) dried (magnesium sulfate) filtered the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate)

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

Procedure: The title compound, ISP-MS: m/e=425.3, 427.3 (M+H+), was prepared in accordance with the general method of example 12b) from 6-bromo-1H-indole-2-carboxylic acid ethyl ester and (S)-5-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester.

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

Procedure: The title compound was prepared in accordance with Example 1, using 6-bromoindole-2-carboxylic acid ethyl ester, 4-isopropoxyphenylboronic acid and 4-bromo-1-isopropoxybenzene.

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

Procedure: Using general procedure B, 6-bromo-1H-indole-2-carboxylic acid ethyl ester was coupled with 1-bromomethyl-naphthalene and the product obtained was hydrolyzed to give the title compound as white solid. MS: 380.1 ([M−H]−). the product obtained

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

Procedure: Using general procedure B, 6-bromo-1H-indole-2-carboxylic acid ethyl ester was coupled with 1-bromomethyl-naphthalene and the product obtained was hydrolyzed to give the title compound as white solid. MS: 380.1 ([M−H]−). the product obtained

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

Procedure: The title compound, ISP-MS: m/e=425.3, 427.3 (M+H+), was prepared in accordance with the general method of example 12b) from 6-bromo-1H-indole-2-carboxylic acid ethyl ester and (S)-5-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester.

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

Procedure: The title compound, ISP-MS: m/e=425.3, 427.3 (M+H+), was prepared in accordance with the general method of example 12b) from 6-bromo-1H-indole-2-carboxylic acid ethyl ester and (S)-5-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of ethyl 6-bromoindole-2-carboxylate (4.4 g, 16.4 mmol) in DMF (20 mL) was added dropwise over ˜2-3 min to a stirred suspension of sodium hydride (60%, 1.0 g, 25 mmol) in DMF (20 mL) at 0° C. under Ar. The reaction was stirred at 0° C. for 45 min then chloroacetonitrile (2.1 mL, 33 mmol) was added in one portion. The reaction was then heated to 75° C. and stirred for 1 h. After allowing to cool to room temperature the mixture was poured into water (150 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with brine (75 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate) to give the product as a yellow solid (4.8 g, 95%). IR νmax (Nujol)/cm−1 3320, 3089, 2925, 2855, 1898, 1705, 1609, 1530, 1521, 1470, 1449, 1427, 1400, 1394, 1377, 1367, 1336, 1308, 1265, 1205, 1151, 1134,1108, 1054, 1027, 993, 950, 90, 873, 841, 832, 802, 792, 762, 736, 663, 615 and 589; NMR OH (400 MHz; CDCl3) 7.61 (1H, s), 7.57 (1H, d, J.8.5 Hz), 7.37 (1H, d, J 1.5 Hz), 7.35 (1H, dd, J 8.5 Hz, 1.5 Hz), 5.57 (2H, s), 4.45 (2H, q, J 7.2 Hz), 1.42 (3H, t, J 7.2 Hz). The reaction was then heated to 75° C. stirred for 1 h to cool to room temperature the mixture extracted with ethyl acetate (3×75 mL) The combined organic extracts were washed with brine (75 mL) dried (magnesium sulfate) filtered the solvent removed under vacuum to leave a crude solid which was purified by flash column chromatography (SiO2; ethyl acetate)

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