2-氯乙氧基三甲基硅烷

反应条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° C. for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). After cooling to ambient temperature filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide ( 10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide ( 10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask is charged with ethanesulfonic acid [5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide (example 226, 200 mg, 0.634 mmol) and DMF (3 mL). The reaction is cooled to 0° C. and sodium hydride (38.0 mg, 0.951 mmol) is added. The reaction is stirred at room temperature for 10 min, then 2-chloro-ethoxytrimethylsilane (0.154 mL, 0.951 mmol) is added. The reaction is stirred at 100° C. for 16 h then cooled to room temperature. Aqueous 1M HCl (1 mL) is added and stirring is continued for 30 min. The mixture is purified using an Xbridge C18 eluting with a 10 to 100% acetonitrile-water gradient to afford ethanesulfonic acid (2-hydroxy-ethyl)-[5-(1-methyl-1H-indol-2-yl)-pyridin-3-yl]-amide. MS (ESI) m/z 360.1 (M+H)+. 1H NMR (400 MHz, MeOD) δ ppm 1.42 (t, J=7.3 Hz, 3H), 3.29 (t, 2H), 3.70 (t, J=5.6 Hz, 2H), 3.84 (s, 3H), 3.96 (t, J=5.6 Hz, 2H), 6.75 (s, 1H), 7.14 (td, J=7.5, 0.9 Hz, 1H), 7.28 (td, J=7.7, 1.0 Hz, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 8.18 (t, J=2.1 Hz, 1H), 8.71 (d, J=2.3 Hz, 1H), 8.75 (d, J=1.8 Hz, 1H). HRMS (ESI) m/z 360.1383 [(M+H)+ Calcd for C18H12N3O3S 360.1376]. The reaction is stirred at 100° C. for 16 h then cooled to room temperature stirring is continued for 30 min The mixture is purified C18 eluting with a 10 to 100% acetonitrile-water gradient

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask is charged with 5-chloro-3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 2, 1.0 g, 3.58 mmol) and THF (20 mL) and cooled to 0° C. KHMDS (0.5 M in toluene, 17.9 mL, 8.95 mmol) is added and the mixture is stirred at room temperature for 30 min, followed by addition of (2-chloro-ethoxy)-trimethylsilane (1.06 mL, 8.95 mmol). The reaction mixture is stirred for 48 h at 60° C. After cooling to room temperature, aqueous 1M HCl (30 mL) is added and the mixture is stirred at room temperature for 30 min, then washed with water and extracted with ethyl acetate twice. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 1:4) to afford 2-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethanol as a solid. 1H NMR (400 MHz, MeOD) δ ppm 2.22 (s, 3H), 3.69 (t, J=5.9 Hz, 2H), 4.18 (t, J=5.8 Hz, 2H), 7.21 (dd, J=8.6, 2.0 Hz, 1H), 7.47 (d, J=8.6 Hz, 1H), 7.57 (d, J=1.8 Hz, 1H), 7.61-7.67 (m, 1H), 8.01 (dt, J=7.9, 2.0 Hz, 1H), 8.61-8.71 (m, 2H). HRMS (ESI) m/z 287.0953 [(M+H)+ Calcd for C16H16ClN2O: 287.0951]. The reaction mixture is stirred for 48 h at 60° C After cooling to room temperature the mixture is stirred at room temperature for 30 min washed with water extracted with ethyl acetate twice The organic layer is dried over sodium sulfate concentrated in vacuo The residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 1:4)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

反应条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° C. for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). After cooling to ambient temperature filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)

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

实验步骤: A mixture of p-nitrophenol (1.39 g, 10 mmol), 2-chloroethoxytrimethylsilane (3.2 ml, 20 mmol), potassium carbonate (4.15 g, 30 mmol), cesium carbonate (163 mg, 0.5 mmol), and sodium iodide (149 mg, 1 mmol) in N,N-dimethylformamide (10 ml) is heated at 75° for 19.5 hours. After cooling to ambient temperature, the mixture is diluted with ethyl acetate and filtered. The filtrate is washed with saturated aqueous sodium bicarbonate, then washed 2× with water, dried over magnesium sulfate, filtered, concentrated in vacuo, and purified on Silica gel (1:1 ethyl acetate/hexanes) to give 4-nitro-(2-Hydroxyethoxy)benzene (1.25 g). is heated at 75° for 19.5 hours filtered The filtrate is washed with saturated aqueous sodium bicarbonate washed 2× with water dried over magnesium sulfate filtered concentrated in vacuo purified on Silica gel (1:1 ethyl acetate/hexanes)