1-methyl-4-[[(2S)-pyrrolidin-2-yl]methyl]piperazine

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

Procedure: The title compound was prepared from 2,3-dioxo-2,3-dihydro-1H-indole-5-sulfonylchloride and 1-methyl-4-[(2S)-pyrrolidin-2-ylmethyl]piperazine according to a procedure similar to that of step 1 of Example 12. NMR (400 Mz, DMSO-d6): consistent.

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

Procedure: To a flame dried 3 neck 250 mL round bottom flask fitted with dry ice condenser, ammonia (50 mL) was condensed at −78° C. using an acetone bath. 1-Methyl-4-({(2S)-1-[(4-methylphenyl)sulfonyl]pyrrolidin-2-yl}methyl)piperazine (2.562 g, 7.790 mmol) dissolved in THF (40 mL), EtOH (2 mL) and NH3 (40 mL) was transferred via syringe into the reaction vessel. Lithium (0.500 g, 72.000 mmol) was added by small pieces into the stirred solution. Acetone bath was then removed and the reaction was allowed to reflux for 2 hours and then warmed up to rt. The reaction was quenched with H2O (50 mL) basified to pH 11 with ammonium hydroxide and extracted with EtOAc (3×). The aqueous layer was re-extracted with CH2Cl2/MeOH (90/10) and the combined organic extracts were dried over Na2SO4, filtered and concentrated to give the title compound as a yellow oil (1.300 g, 93% ). NMR (400 Mz, DMSO-d6): consistent. Reference: (Tetrahedron, 43(14), 3289, 1987). To a flame dried 3 neck 250 mL round bottom flask fitted with dry ice condenser condensed at −78° C. Acetone bath was then removed to reflux for 2 hours The reaction was quenched with H2O (50 mL) extracted with EtOAc (3×) The aqueous layer was re-extracted with CH2Cl2/MeOH (90/10) the combined organic extracts were dried over Na2SO4 filtered concentrated

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

Procedure: The title compound is prepared analogously to Example 31 from 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one and (S)-(+)-2-[(4-methyl-1-piperazinyl) methyl]pyrrolidine to give colorless crystals, mp. 182°-185° C. (D) (from ethyl acetate/methanol 99:1 v/v); [α]D20 =-11.2° (ethanol).

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

Procedure: The title compound is prepared analogously to Example 31 from 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one and (S)-(+)-2-[(4-methyl-1-piperazinyl) methyl]pyrrolidine to give colorless crystals, mp. 182°-185° C. (D) (from ethyl acetate/methanol 99:1 v/v); [α]D20 =-11.2° (ethanol).

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

Procedure: The title compound is prepared analogously to Example 31 from 5-(chloroacetyl)-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one and (S)-(+)-2-[(4-methyl-1-piperazinyl)methyl]pyrrolidine to give colorless crystals, mp. 168°-170° C. (ethyl acetate). [α]D20 =-18.9° C. (ethanol). RF 0.33 (Merck ready-made TLC plates, silica gel 60 F-254; eluant: dichloromethane/methanol/cyclohexane/conc. ammonia [120:24:30:2]). A second isomer (RF 0.30) can be detected in the mother liquors by thin layer chromatography.

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

Procedure: The title compound was prepared from 2,3-dioxo-2,3-dihydro-1H-indole-5-sulfonylchloride and 1-methyl-4-[(2S)-pyrrolidin-2-ylmethyl]piperazine according to a procedure similar to that of step 1 of Example 12. NMR (400 Mz, DMSO-d6): consistent.

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

Procedure: To a flame dried 3 neck 250 mL round bottom flask fitted with dry ice condenser, ammonia (50 mL) was condensed at −78° C. using an acetone bath. 1-Methyl-4-({(2S)-1-[(4-methylphenyl)sulfonyl]pyrrolidin-2-yl}methyl)piperazine (2.562 g, 7.790 mmol) dissolved in THF (40 mL), EtOH (2 mL) and NH3 (40 mL) was transferred via syringe into the reaction vessel. Lithium (0.500 g, 72.000 mmol) was added by small pieces into the stirred solution. Acetone bath was then removed and the reaction was allowed to reflux for 2 hours and then warmed up to rt. The reaction was quenched with H2O (50 mL) basified to pH 11 with ammonium hydroxide and extracted with EtOAc (3×). The aqueous layer was re-extracted with CH2Cl2/MeOH (90/10) and the combined organic extracts were dried over Na2SO4, filtered and concentrated to give the title compound as a yellow oil (1.300 g, 93% ). NMR (400 Mz, DMSO-d6): consistent. Reference: (Tetrahedron, 43(14), 3289, 1987). To a flame dried 3 neck 250 mL round bottom flask fitted with dry ice condenser condensed at −78° C. Acetone bath was then removed to reflux for 2 hours The reaction was quenched with H2O (50 mL) extracted with EtOAc (3×) The aqueous layer was re-extracted with CH2Cl2/MeOH (90/10) the combined organic extracts were dried over Na2SO4 filtered concentrated

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

Procedure: The title compound is prepared analogously to Example 31 from 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one and (S)-(+)-2-[(4-methyl-1-piperazinyl) methyl]pyrrolidine to give colorless crystals, mp. 182°-185° C. (D) (from ethyl acetate/methanol 99:1 v/v); [α]D20 =-11.2° (ethanol).

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

Procedure: The title compound is prepared analogously to Example 31 from 5-(chloroacetyl)-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one and (S)-(+)-2-[(4-methyl-1-piperazinyl)methyl]pyrrolidine to give colorless crystals, mp. 168°-170° C. (ethyl acetate). [α]D20 =-18.9° C. (ethanol). RF 0.33 (Merck ready-made TLC plates, silica gel 60 F-254; eluant: dichloromethane/methanol/cyclohexane/conc. ammonia [120:24:30:2]). A second isomer (RF 0.30) can be detected in the mother liquors by thin layer chromatography.