4-bromo-7-methoxy-1H-indole

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

Procedure: 5-Bromo-7-methoxyindole CV was prepared from 5-bromo-2-nitroanisole using the procedure described above for preparation of 4-bromo-7-methoxyindole LII (Example 13).

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

Procedure: 5-Bromo-7-methoxyindole CV was prepared from 5-bromo-2-nitroanisole using the procedure described above for preparation of 4-bromo-7-methoxyindole LII (Example 13).

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

Procedure: To a −60° C. solution of 4-bromo-2-nitroanisole (7.89 g, 33.3 mmol) in THF (300 was added vinylmagnesium bromide (1 M in THF, 100 ml, 0.1 mol) while maintaining the reaction temperature below −40° C. The resulting mixture was stirred allowing the temperature to rise to −40° C. in 2 hours. The reaction mixture was then quenched with a saturated solution of NH4Cl (700 ml) and extracted with Et2O (200 ml). The combined organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and purified through flash chromatography affording 4-bromo-7-methoxyindole LII (594 mg, 8% yield). while maintaining the reaction temperature below −40° C The reaction mixture was then quenched with a saturated solution of NH4Cl (700 ml) extracted with Et2O (200 ml) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated purified through flash chromatography

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

Procedure: To a −60° C. solution of 4-bromo-2-nitroanisole (7.89 g, 33.3 mmol) in THF (300 was added vinylmagnesium bromide (1 M in THF, 100 ml, 0.1 mol) while maintaining the reaction temperature below −40° C. The resulting mixture was stirred allowing the temperature to rise to −40° C. in 2 hours. The reaction mixture was then quenched with a saturated solution of NH4Cl (700 ml) and extracted with Et2O (200 ml). The combined organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and purified through flash chromatography affording 4-bromo-7-methoxyindole LII (594 mg, 8% yield). while maintaining the reaction temperature below −40° C The reaction mixture was then quenched with a saturated solution of NH4Cl (700 ml) extracted with Et2O (200 ml) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated purified through flash chromatography

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-[(E)-2-(6-bromo-3-methoxy-2-nitrophenyl)vinyl]pyrrolidine (1.3 g, 3.97 mmol) in THF (6 mL) and methanol (6 mL) was added Raney Ni (≈500 mg) followed by hydrazine (0.19 mL). (CAUTION: Exothermic reaction with vigorous gas evolution). Hydrazine (0.19 mL) was added again, two times, after 30 min and 1 h. The reaction was stirred at 45° C. for 2 h, filtered through a pad of celite. The filtrate was concentrated in vacuo and the residue purified by chromatography over silica gel eluting with EtOAc/hexane to afford pure 4-bromo-7-methoxy-1H-indole. 1H NMR (400 MHz, CDCl3) δ=3.94 (s, 3H), 6.52 (d, J=8.08 Hz, 1H), 6.56 (dd, J=3.16, 2.40 Hz, 1H), 7.17 (d, J=8.08 Hz, 1H), 7.22 (t, J=2.78 Hz, 1H) and 8.47 (br. s., 1H); MS (ES+): m/z 226.12 [MH+]. (CAUTION: Exothermic reaction with vigorous gas evolution) 1 h filtered through a pad of celite The filtrate was concentrated in vacuo the residue purified by chromatography over silica gel eluting with EtOAc/hexane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-[(E)-2-(6-bromo-3-methoxy-2-nitrophenyl)vinyl]pyrrolidine (1.3 g, 3.97 mmol) in THF (6 mL) and methanol (6 mL) was added Raney Ni (≈500 mg) followed by hydrazine (0.19 mL). (CAUTION: Exothermic reaction with vigorous gas evolution). Hydrazine (0.19 mL) was added again, two times, after 30 min and 1 h. The reaction was stirred at 45° C. for 2 h, filtered through a pad of celite. The filtrate was concentrated in vacuo and the residue purified by chromatography over silica gel eluting with EtOAc/hexane to afford pure 4-bromo-7-methoxy-1H-indole. 1H NMR (400 MHz, CDCl3) δ=3.94 (s, 3H), 6.52 (d, J=8.08 Hz, 1H), 6.56 (dd, J=3.16, 2.40 Hz, 1H), 7.17 (d, J=8.08 Hz, 1H), 7.22 (t, J=2.78 Hz, 1H) and 8.47 (br. s., 1H); MS (ES+): m/z 226.12 [MH+]. (CAUTION: Exothermic reaction with vigorous gas evolution) 1 h filtered through a pad of celite The filtrate was concentrated in vacuo the residue purified by chromatography over silica gel eluting with EtOAc/hexane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-[(E)-2-(6-bromo-3-methoxy-2-nitrophenyl)vinyl]pyrrolidine (1.3 g, 3.97 mmol) in THF (6 mL) and methanol (6 mL) was added Raney Ni (≈500 mg) followed by hydrazine (0.19 mL). (CAUTION: Exothermic reaction with vigorous gas evolution). Hydrazine (0.19 mL) was added again, two times, after 30 min and 1 h. The reaction was stirred at 45° C. for 2 h, filtered through a pad of celite. The filtrate was concentrated in vacuo and the residue purified by chromatography over silica gel eluting with EtOAc/hexane to afford pure 4-bromo-7-methoxy-1H-indole. 1H NMR (400 MHz, CDCl3) δ=3.94 (s, 3H), 6.52 (d, J=8.08 Hz, 1H), 6.56 (dd, J=3.16, 2.40 Hz, 1H), 7.17 (d, J=8.08 Hz, 1H), 7.22 (t, J=2.78 Hz, 1H) and 8.47 (br. s., 1H); MS (ES+): m/z 226.12 [MH+]. (CAUTION: Exothermic reaction with vigorous gas evolution) 1 h filtered through a pad of celite The filtrate was concentrated in vacuo the residue purified by chromatography over silica gel eluting with EtOAc/hexane

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

Procedure: 5-Bromo-7-methoxyindole CV was prepared from 5-bromo-2-nitroanisole using the procedure described above for preparation of 4-bromo-7-methoxyindole LII (Example 13).

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

Procedure: To a −60° C. solution of 4-bromo-2-nitroanisole (7.89 g, 33.3 mmol) in THF (300 was added vinylmagnesium bromide (1 M in THF, 100 ml, 0.1 mol) while maintaining the reaction temperature below −40° C. The resulting mixture was stirred allowing the temperature to rise to −40° C. in 2 hours. The reaction mixture was then quenched with a saturated solution of NH4Cl (700 ml) and extracted with Et2O (200 ml). The combined organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and purified through flash chromatography affording 4-bromo-7-methoxyindole LII (594 mg, 8% yield). while maintaining the reaction temperature below −40° C The reaction mixture was then quenched with a saturated solution of NH4Cl (700 ml) extracted with Et2O (200 ml) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated purified through flash chromatography

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-[(E)-2-(6-bromo-3-methoxy-2-nitrophenyl)vinyl]pyrrolidine (1.3 g, 3.97 mmol) in THF (6 mL) and methanol (6 mL) was added Raney Ni (≈500 mg) followed by hydrazine (0.19 mL). (CAUTION: Exothermic reaction with vigorous gas evolution). Hydrazine (0.19 mL) was added again, two times, after 30 min and 1 h. The reaction was stirred at 45° C. for 2 h, filtered through a pad of celite. The filtrate was concentrated in vacuo and the residue purified by chromatography over silica gel eluting with EtOAc/hexane to afford pure 4-bromo-7-methoxy-1H-indole. 1H NMR (400 MHz, CDCl3) δ=3.94 (s, 3H), 6.52 (d, J=8.08 Hz, 1H), 6.56 (dd, J=3.16, 2.40 Hz, 1H), 7.17 (d, J=8.08 Hz, 1H), 7.22 (t, J=2.78 Hz, 1H) and 8.47 (br. s., 1H); MS (ES+): m/z 226.12 [MH+]. (CAUTION: Exothermic reaction with vigorous gas evolution) 1 h filtered through a pad of celite The filtrate was concentrated in vacuo the residue purified by chromatography over silica gel eluting with EtOAc/hexane

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-bromo-4-methoxy-2-methyl-3-nitro-benzene (31 g, 0.126 mol) in DMF (150 mL) was added dimethylformamide dimethylacetal (27 mL) and pyrrolidine (10.5 mL, 0.127 mol). The mixture was heated at 90° C. for 18 h and cooled to r.t. The mixture was diluted with water and extracted with CH2Cl2. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was dissolved into HOAc (50 mL) and added dropwise to a solution of Fe (20.5 g, 0.37 mol) in boiling HOAc (150 mL). The mixture was refluxed for 1 h and cooled to r.t., water added and the mixture was neutralised with Na2CO3, and extracted with CH2Cl2. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by Prep-TLC (PE/EtOAc=5/1) to give the title compound (13 g, 44%). cooled to r.t extracted with CH2Cl2 The organic phase was dried over Na2SO4 filtered concentrated The residue was dissolved into HOAc (50 mL) The mixture was refluxed for 1 h cooled to r.t. extracted with CH2Cl2 The organic phase was dried over Na2SO4 filtered concentrated The residue was purified by Prep-TLC (PE/EtOAc=5/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-bromo-4-methoxy-2-methyl-3-nitro-benzene (31 g, 0.126 mol) in DMF (150 mL) was added dimethylformamide dimethylacetal (27 mL) and pyrrolidine (10.5 mL, 0.127 mol). The mixture was heated at 90° C. for 18 h and cooled to r.t. The mixture was diluted with water and extracted with CH2Cl2. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was dissolved into HOAc (50 mL) and added dropwise to a solution of Fe (20.5 g, 0.37 mol) in boiling HOAc (150 mL). The mixture was refluxed for 1 h and cooled to r.t., water added and the mixture was neutralised with Na2CO3, and extracted with CH2Cl2. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by Prep-TLC (PE/EtOAc=5/1) to give the title compound (13 g, 44%). cooled to r.t extracted with CH2Cl2 The organic phase was dried over Na2SO4 filtered concentrated The residue was dissolved into HOAc (50 mL) The mixture was refluxed for 1 h cooled to r.t. extracted with CH2Cl2 The organic phase was dried over Na2SO4 filtered concentrated The residue was purified by Prep-TLC (PE/EtOAc=5/1)