5-溴-1H-吡咯-2-羧酸甲酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-Bromo-1H-pyrrole-2-carboxylic acid methyl ester (1.49 mmol, 0.30 g, prepared according to the procedure described in Method 4 of Example 2) in NMP (10 ml) was treated with triphenylarsine (0.30 mmol, 91 mg), tris(dibenzylideneacetone) dipalladium(0) (0.07 mmol, 68 mg), and 4-(trimethylstannyl)-isoquinoline (2.22 mmol, 0.65 g), then heated to reflux under an argon atmosphere overnight. The resulting mixture was concentrated under reduced pressure, then purified by silica gel chromatography to provide 0.21 g (55%) of 5-isoquinolin-4-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ9.81 (1H, br s), 9.35 (1H, s), 8.66 (1H, s), 8.31 (1H, d, J=8.5), 8.10 (1H, d, J=8.1), 7.91 (1H, t, J=15.2), 7.79 (1H, t, J 15.2), 7.11 (1H, dd, J=3.8, 2.5), 6.64 (1H, dd, J=3.7, 2.7), 3.90 (3H, s). heated to reflux under an argon atmosphere overnight The resulting mixture was concentrated under reduced pressure purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Argon gas was bubbled 15 min through a solution of 5-bromo-1H-pyrrole-2-carboxylic acid methyl ester (10.0 mmol, 2.04 g), 1-naphthylboronic acid (30.0 mmol, 5.16 g), 2M aqueous sodium carbonate (20 ml), and DMF (150 ml). The mixture was then treated with tris(dibenzylidienacetone)dipalladium (0) (0.50 mmol, 0.46 g), and triphenylarsine (2.0 mmol, 0.61 g), then heated to reflux under argon for 12 h. The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml). The organics were filtered through celite, washed with brine (3×50 ml), then concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 2.05 g (81%) of 5-naphthalen-1-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ9.37 (1H, s), 8.22-8.17 (1H, m), 8.16-7.89 (2H, m), 7.59-7.50 (4H, m), 7.88 (1H, dd, J=3.9, 2.7), 6.22 (1H, dd, J=3.8. 2.6), 3.88 (3H, s). heated to reflux under argon for 12 h The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml) The organics were filtered through celite washed with brine (3×50 ml) concentrated under reduced pressure the residue was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of pyrrole-2-carboxylic acid methyl ester (79.9 mmol, 10.0 g) in carbon tetrachloride (300 ml) was heated to 70° C., then treated dropwise with a solution of bromine (99.9 mmol, 126.0 ml) in carbon tetrachloride (200 ml). The reaction was initiated by the addition of iodine (40 mg). After the addition was complete, the reaction was held at 70° C. for 10 min, then cooled to room temperature using an ice bath. The mixture was washed with 10% aqueous sodium carbonate (100 ml), followed by water (100 ml). The organics were concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 4.5 g (27%) of 5-bromo-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ9.29 (1H, s), 6.80 (1H, dd, J=3.9, 2.7), 6.23 (1H, dd, J=3.8, 2.6), 3.88 (3H, s). After the addition The mixture was washed with 10% aqueous sodium carbonate (100 ml) The organics were concentrated under reduced pressure the residue was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-Bromo-1H-pyrrole-2-carboxylic acid methyl ester (1.49 mmol, 0.30 g, prepared according to the procedure described in Method 4 of Example 2) in NMP (10 ml) was treated with triphenylarsine (0.30 mmol, 91 mg), tris(dibenzylideneacetone) dipalladium(0) (0.07 mmol, 68 mg), and 4-(trimethylstannyl)-isoquinoline (2.22 mmol, 0.65 g), then heated to reflux under an argon atmosphere overnight. The resulting mixture was concentrated under reduced pressure, then purified by silica gel chromatography to provide 0.21 g (55%) of 5-isoquinolin-4-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ 9.81 (1H, br s), 9.35 (1H, s), 8.66 (1H, s), 8.31 (1H, d, J=8.5), 8.10 (1H, d, J=8.1), 7.91 (1H, t, J=15.2), 7.79 (1H, t, J=15.2), 7.11 (1H, dd, J=3.8, 2.5), 6.64 (1H, dd, J=3.7, 2.7), 3.90 (3H, s). heated to reflux under an argon atmosphere overnight The resulting mixture was concentrated under reduced pressure purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-Bromo-1H-pyrrole-2-carboxylic acid methyl ester (1.49 mmol, 0.30 g, prepared according to the procedure described in Method 4 of Example 2) in NMP (10 ml) was treated with triphenylarsine (0.30 mmol, 91 mg), tris(dibenzylideneacetone) dipalladium(0) (0.07 mmol, 68 mg), and 4-(trimethylstannyl)-isoquinoline (2.22 mmol, 0.65 g), then heated to reflux under an argon atmosphere overnight. The resulting mixture was concentrated under reduced pressure, then purified by silica gel chromatography to provide 0.21 g (55%) of 5-isoquinolin-4-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ 9.81 (1H, br s), 9.35 (1H, s), 8.66 (1H, s), 8.31 (1H, d, J=8.5), 8.10 (1H, d, J=8.1), 7.91 (1H, t, J=15.2), 7.79 (1H, t, J=15.2), 7.11 (1H, dd, J=3.8, 2.5), 6.64 (1H, dd, J=3.7, 2.7), 3.90 (3H, s). heated to reflux under an argon atmosphere overnight The resulting mixture was concentrated under reduced pressure purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Argon gas was bubbled 15 min through a solution of 5-bromo-1H-pyrrole-2-carboxylic acid methyl ester (10.0 mmol, 2.04 g), 1-naphthylboronic acid (30.0 mmol, 5.16 g), 2M aqueous sodium carbonate (20 ml), and DMF (150 ml). The mixture was then treated with tris(dibenzylidienacetone)dipalladium (0) (0.50 mmol, 0.46 g), and triphenylarsine (2.0 mmol, 0.61 g), then heated to reflux under argon for 12 h. The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml). The organics were filtered through celite, washed with brine (3×50 ml), then concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 2.05 g (81%) of 5-naphthalen-1-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ 9.37 (1H, s), 8.22-8.17 (1H, m), 8.16-7.89 (2H, m), 7.59-7.50 (4H, m), 7.88 (1H, dd, J=3.9, 2.7), 6.22 (1H, dd, J=3.8. 2.6), 3.88 (3H, s). heated to reflux under argon for 12 h The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml) The organics were filtered through celite washed with brine (3×50 ml) concentrated under reduced pressure the residue was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of pyrrole-2-carboxylic acid methyl ester (79.9 mmol, 10.0 g) in carbon tetrachloride (300 ml) was heated to 70° C., then treated dropwise with a solution of bromine (99.9 mmol, 126.0 ml) in carbon tetrachloride (200 ml). The reaction was initiated by the addition of iodine (40 mg). After the addition was complete, the reaction was held at 70° C. for 10 min, then cooled to room temperature using an ice bath. The mixture was washed with 10% aqueous sodium carbonate (100 ml), followed by water (100 ml). The organics were concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 4.5 g (27%) of 5-bromo-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ 9.29 (1H, s), 6.80 (1H, dd, J=3.9, 2.7), 6.23 (1H, dd, J=3.8, 2.6), 3.88 (3H, s). After the addition The mixture was washed with 10% aqueous sodium carbonate (100 ml) The organics were concentrated under reduced pressure the residue was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-Bromo-1H-pyrrole-2-carboxylic acid methyl ester (1.49 mmol, 0.30 g, prepared according to the procedure described in Method 4 of Example 2) in NMP (10 ml) was treated with triphenylarsine (0.30 mmol, 91 mg), tris(dibenzylideneacetone) dipalladium(0) (0.07 mmol, 68 mg), and 4-(trimethylstannyl)-isoquinoline (2.22 mmol, 0.65 g), then heated to reflux under an argon atmosphere overnight. The resulting mixture was concentrated under reduced pressure, then purified by silica gel chromatography to provide 0.21 g (55%) of 5-isoquinolin-4-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ9.81 (1H, br s), 9.35 (1H, s), 8.66 (1H, s), 8.31 (1H, d, J=8.5), 8.10 (1H, d, J=8.1), 7.91 (1H, t, J=15.2), 7.79 (1H, t, J 15.2), 7.11 (1H, dd, J=3.8, 2.5), 6.64 (1H, dd, J=3.7, 2.7), 3.90 (3H, s). heated to reflux under an argon atmosphere overnight The resulting mixture was concentrated under reduced pressure purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Argon gas was bubbled 15 min through a solution of 5-bromo-1H-pyrrole-2-carboxylic acid methyl ester (10.0 mmol, 2.04 g), 1-naphthylboronic acid (30.0 mmol, 5.16 g), 2M aqueous sodium carbonate (20 ml), and DMF (150 ml). The mixture was then treated with tris(dibenzylidienacetone)dipalladium (0) (0.50 mmol, 0.46 g), and triphenylarsine (2.0 mmol, 0.61 g), then heated to reflux under argon for 12 h. The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml). The organics were filtered through celite, washed with brine (3×50 ml), then concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 2.05 g (81%) of 5-naphthalen-1-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ9.37 (1H, s), 8.22-8.17 (1H, m), 8.16-7.89 (2H, m), 7.59-7.50 (4H, m), 7.88 (1H, dd, J=3.9, 2.7), 6.22 (1H, dd, J=3.8. 2.6), 3.88 (3H, s). heated to reflux under argon for 12 h The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml) The organics were filtered through celite washed with brine (3×50 ml) concentrated under reduced pressure the residue was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Argon gas was bubbled 15 min through a solution of 5-bromo-1H-pyrrole-2-carboxylic acid methyl ester (10.0 mmol, 2.04 g), 1-naphthylboronic acid (30.0 mmol, 5.16 g), 2M aqueous sodium carbonate (20 ml), and DMF (150 ml). The mixture was then treated with tris(dibenzylidienacetone)dipalladium (0) (0.50 mmol, 0.46 g), and triphenylarsine (2.0 mmol, 0.61 g), then heated to reflux under argon for 12 h. The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml). The organics were filtered through celite, washed with brine (3×50 ml), then concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 2.05 g (81%) of 5-naphthalen-1-yl-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ9.37 (1H, s), 8.22-8.17 (1H, m), 8.16-7.89 (2H, m), 7.59-7.50 (4H, m), 7.88 (1H, dd, J=3.9, 2.7), 6.22 (1H, dd, J=3.8. 2.6), 3.88 (3H, s). heated to reflux under argon for 12 h The mixture was partitioned between ethyl acetate (500 ml) and water (150 ml) The organics were filtered through celite washed with brine (3×50 ml) concentrated under reduced pressure the residue was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of pyrrole-2-carboxylic acid methyl ester (79.9 mmol, 10.0 g) in carbon tetrachloride (300 ml) was heated to 70° C., then treated dropwise with a solution of bromine (99.9 mmol, 126.0 ml) in carbon tetrachloride (200 ml). The reaction was initiated by the addition of iodine (40 mg). After the addition was complete, the reaction was held at 70° C. for 10 min, then cooled to room temperature using an ice bath. The mixture was washed with 10% aqueous sodium carbonate (100 ml), followed by water (100 ml). The organics were concentrated under reduced pressure and the residue was purified by silica gel chromatography to provide 4.5 g (27%) of 5-bromo-1H-pyrrole-2-carboxylic acid methyl ester. 1H NMR (CDCl3) δ9.29 (1H, s), 6.80 (1H, dd, J=3.9, 2.7), 6.23 (1H, dd, J=3.8, 2.6), 3.88 (3H, s). After the addition The mixture was washed with 10% aqueous sodium carbonate (100 ml) The organics were concentrated under reduced pressure the residue was purified by silica gel chromatography