3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-1H-indole

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2 ·1/8 CH2Cl2C,75.42; H,8.18; N,12 46 Found: C,75 50; H,8 51; N,12 09. [α]25D =+60.2° (c=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH)

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2:MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2. 1/8 CH2Cl2C, 75.42; H, 8.18; N, 12.46 Found: C, 75.50; H, 8.51; N, 12.09⟦alpha⟧sup.25D =+60.2° (c=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2:MeOH:NH4OH)

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2:MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2. 1/8 CH2Cl2C, 75.42; H, 8.18; N, 12.46 Found: C, 75.50; H, 8.51; N, 12.09⟦alpha⟧sup.25D =+60.2° (c=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2:MeOH:NH4OH)

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2 ·1/8 CH2Cl2C,75.42; H,8.18; N,12.46. Found: C,75.50; H,8.51; N,12.09⟦alpha⟧sup.25D =+60.2° (C=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH)

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2 ·1/8 CH2Cl2C,75.42; H,8.18; N,12.46. Found: C,75.50; H,8.51; N,12.09⟦alpha⟧sup.25D =+60.2° (C=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH)

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2 ·1/8 CH2Cl2C, 75.42; H, 8.18; N,12.46 Found: C,75.50; H,8.51; N,12.09⟦alpha⟧sup.25D =+60.2° (c=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH)

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2 ·1/8 CH2Cl2C, 75.42; H, 8.18; N,12.46 Found: C,75.50; H,8.51; N,12.09⟦alpha⟧sup.25D =+60.2° (c=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH)

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2 · 1/8CH2Cl2C,75.42; H,8.18; N,12.46 Found: C,75.50; H,8.51; N,12.09⟦alpha⟧sup.25D =+60.2° (c=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH)

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

Procedure: Sodium bis(trimethylsilyl)amide (0.25 mL, 1M in THF, 0.25 mmol) was added to a solution of (R)-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole (Example 3e, 25.8 mg, 0.12 mmol) in THF (1.5 mL) at -78° C. and the mixture was stirred for 1 h. Phenylsulfonyl chloride (50 μL, 0.39 mmol) was added and the mixture stirred at room temperature for 1 h. prior to quenching with water (6 drops) and silica gel (~1 g). Purification using solid phase extraction tubes (1000 mg silica) eluting with 2M methanolic ammonia in dichloromethane (0-4%) yielded (R)-3-(1-methyl-2-pyrrolidinylmethyl)-1-phenylsulfonylindole (19.7 mg, 46%, HRMS-FAB+ for C20H22N2O2S: calculated MH+ :355.14801; found MH+ :355.14837). the mixture stirred at room temperature for 1 h. to quenching with water (6 drops) and silica gel (~1 g) Purification solid phase extraction tubes (1000 mg silica) eluting with 2M methanolic ammonia in dichloromethane (0-4%)

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

Procedure: (R)-3-(N-Methylpyrrolidin-2-ylmethyl)indole and 2-chloro-3-nitropyridine were used. Triethylamine was used as base, acetonitrile was used as solvent, and the reaction was heated at reflux for 3.5 hours. Chromatography afforded the title compound (81%) as a dark red foam: 1H NMR (CDCl3) δ10.11 (br s, 1H), 8.52 (dd, J=1.7 Hz, J=1.8 and 8.4 Hz, 1H), 8.43 (1.8 and 4.5 Hz; 1H), 8.33 (br s, 1H), 7.77 (d, 1H), 7.35 (d, J=8.7 Hz, 1H), 7.26 (dd, J=2.0 and 8.6 Hz, 1H), 7.03 (d, J=2.1 Hz, 1H), 6.74 (dd, J=4.44 and 8.4 Hz, 1H), 3.21-3.12 (m, 2H), 2.68-2.58 (m, 1H), 2.54-2.46 (m, 1H), 2.47 (s, 3H), 2.28-2.18 (m, 1H), 1.89-1.73 (m, 2H), 1.73-1.54 (m, 2H); 13C NMR (CDCl3) δ155.7, 151.5, 135.5, 134.3, 129.5, 128.2, 128.1, 123.1, 119.4, 114.3, 113.0, 111.4, 66.7, 57.5, 40.8, 31.5, 29.9, 21.9, Anal. calcd. for C19H21N5O2.1/3H2O: C, 63.85; H, 6.11; N, 19.59. Found: C, 63.86; H, 5.86; N, 19.31. the reaction was heated at reflux for 3.5 hours

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

Procedure: (R)-3-(N-Methylpyrrolidin-2-ylmethyl)indole and 2-chloro-3-nitropyridine were used. Triethylamine was used as base, acetonitrile was used as solvent, and the reaction was heated at reflux for 3.5 hours. Chromatography afforded the title compound (81%) as a dark red foam: 1H NMR (CDCl3) δ 10.11 (br s, 1H), 8.52 (dd, J=1.8 and 8.4 Hz, 1H), 8.43 (1.8 and 4.5 Hz, 1H), 8.33 (br s, 1H), 7.77 (d, J=1.7 Hz, 1H), 7.35 (d, J=8.7 Hz, 1H), 7.26 (dd, J=2.0 and 8.6 Hz, 1H), 7.03 (d, J=2.1 Hz, 1H) 6.74 (dd, J=4.4 and 8.4 Hz, 1H), 3.21-3.12 (m, 2H), 2.68-2.2.58 (m, 1H), 2.54-2.46 (m, 1H), 2.47 (s, 3H), 2.28-2.18 (m, 1H), 1.89-1.73 (m, 2H), 1.73-1.54 (m, 2H); 13C NMR (CDCl3) δ 155.7, 151.5, 135.5, 134.3, 129.5, 128.2, 128.1, 123.1, 119.4, 114.3, 113.0, 111.4, 66.7, 57.5, 40.8, 31.5, 29.9, 21.9. Anal. calcd for C19H21N5O2.1/3 H2O: C, 63.85; H, 6.11; N, 19.59. Found: C, 63.86; H, 5.86; N, 19.31. the reaction was heated at reflux for 3.5 hours

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

Procedure: (R)-5-Bromo-3-(N-methylpyrrolidin-2-yl-methyl)-1H-indole (60 mg, 0.2 mmol) was dissolved in ethanol (1 mL) and hydrogenated over 10% palladium on carbon (45 mg) at 60 p.s.i. of hydrogen pressure at room temperature for 16 hours. The reaction mixture was evaporated to dryness, and the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate. The organic phase was dried (Na2SO4), and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH) to give the title compound (28 mg). Anal. Calcd for C14H18N2 ·1/8 CH2Cl2C,75.42; H,8.18; N,12 46 Found: C,75 50; H,8 51; N,12 09. [α]25D =+60.2° (c=0.088, CHCl3). The reaction mixture was evaporated to dryness the residue partitioned between ethyl acetate and 10% aqueous sodium carbonate The organic phase was dried (Na2SO4) evaporated in vacuo The resulting residue was purified by column chromatography on silica gel (eluting with 89:10:1 CH2Cl2 :MeOH:NH4OH)