(4S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one

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

Procedure: A suspension of the product from step (c) (1.3 g) and 10% w/w Pd/C (1.0 g) in 30% w/w ethanolic dimethylamine (25 ml) was hydrogenated for 24 hours and filtered through Hyflo. Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours. The mixture was filtered through a silica column using DCM/EtOH/NH4OH (40:8:1) as eluant to give the desired product as a colourless foam (0.3 g). Elemental analysis and 1H NMR were consistent with the proposed structure. filtered through Hyflo Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours The mixture was filtered through a silica column

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

Procedure: A solution of the product from step (b) (2.5 g) and polyphosphate ester (20.0 g) in chloroform (40 ml) was refluxed for 20 minutes. Ice was added to the cooled mixture and the chloroform evaporated in vacuo. The remaining aqueous phase was extracted with ethyl acetate and the combined extracts evaporated in vacuo to give the desired product as a pale yellow oil (1.8 g). Ice was added to the cooled mixture the chloroform evaporated in vacuo The remaining aqueous phase was extracted with ethyl acetate the combined extracts evaporated in vacuo

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

Procedure: A suspension of the product from step (c) (1.3 g) and 10% w/w Pd/C (1.0 g) in 30% w/w ethanolic dimethylamine (25 ml) was hydrogenated for 24 hours and filtered through Hyflo. Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours. The mixture was filtered through a silica column using DCM/EtOH/NH4OH (40:8:1) as eluant to give the desired product as a colourless foam (0.3 g). Elemental analysis and 1H NMR were consistent with the proposed structure. filtered through Hyflo Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours The mixture was filtered through a silica column

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

Procedure: A solution of the product from step (b) (2.5 g) and polyphosphate ester (20.0 g) in chloroform (40 ml) was refluxed for 20 minutes. Ice was added to the cooled mixture and the chloroform evaporated in vacuo. The remaining aqueous phase was extracted with ethyl acetate and the combined extracts evaporated in vacuo to give the desired product as a pale yellow oil (1.8 g). Ice was added to the cooled mixture the chloroform evaporated in vacuo The remaining aqueous phase was extracted with ethyl acetate the combined extracts evaporated in vacuo

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

Procedure: A solution of the product from step (b) (2.5 g) and polyphosphate ester (20.0 g) in chloroform (40 ml) was refluxed for 20 minutes. Ice was added to the cooled mixture and the chloroform evaporated in vacuo. The remaining aqueous phase was extracted with ethyl acetate and the combined extracts evaporated in vacuo to give the desired product as a pale yellow oil (1.8 g). Ice was added to the cooled mixture the chloroform evaporated in vacuo The remaining aqueous phase was extracted with ethyl acetate the combined extracts evaporated in vacuo

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1 g (3.02 mmoles) of the (S)-3-(2-dimethylaminoethyl)-5-(2-oxo-1,3-oxazolidin-4-ylmenthyl)-1H-indol-2-carboxylic acid was suspended in 10 ml of dry quinoline. 20 mg of cuprous oxide was added and the stirred suspension heated to 200° C. under dry nitrogen stream. The reaction mixture was kept at this temperature until no more CO2 was released (15-20 min.). It was left to cool to room temperature and the reaction mixture filtered through decalite. The filtrate was concentrated by vacuum distillation of the solvent, providing a residue which was dissolved with a succinic acid solution and washed three times with 15 ml of dichloromethane. The washed aqueous phase was cooled, the pH adjusted to 12 with a 40% sodium hydroxide solution and extracted three times with 20 ml of dichloromethane. The combined organic phases were dried on anhydrous sodium sulphate and evaporated to dryness. The residue was recrystallised with isopropyl alcohol to give 780 mg (90%) of zolmitriptan as a white solid. (15-20 min.) It was left to cool to room temperature the reaction mixture filtered through decalite The filtrate was concentrated by vacuum distillation of the solvent providing a residue which washed three times with 15 ml of dichloromethane The washed aqueous phase was cooled extracted three times with 20 ml of dichloromethane The combined organic phases were dried on anhydrous sodium sulphate evaporated to dryness The residue was recrystallised with isopropyl alcohol

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

Procedure: A suspension of the product from step (c) (1.3 g) and 10% w/w Pd/C (1.0 g) in 30% w/w ethanolic dimethylamine (25 ml) was hydrogenated for 24 hours and filtered through Hyflo. Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours. The mixture was filtered through a silica column using DCM/EtOH/NH4OH (40:8:1) as eluant to give the desired product as a colourless foam (0.3 g). Elemental analysis and 1H NMR were consistent with the proposed structure. filtered through Hyflo Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours The mixture was filtered through a silica column

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

Procedure: By steps identical to steps (d) to (f) of Synthetic Example 1 and Synthetic Example 2 or steps (d) and (e) of Synthetic Example 1 and Synthetic Example 3 and steps (e) to (h) of Synthetic Example 4, the product from step (a) was converted to (S)-N,N-dimethyl-2-[5-(2-oxo-l,3-oxazolidin-4-ylmethyl)-1H. indol-3-yl]ethylamine.

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1 g (3.02 mmoles) of the (S)-3-(2-dimethylaminoethyl)-5-(2-oxo-1,3-oxazolidin-4-ylmenthyl)-1H-indol-2-carboxylic acid was suspended in 10 ml of dry quinoline. 20 mg of cuprous oxide was added and the stirred suspension heated to 200° C. under dry nitrogen stream. The reaction mixture was kept at this temperature until no more CO2 was released (15-20 min.). It was left to cool to room temperature and the reaction mixture filtered through decalite. The filtrate was concentrated by vacuum distillation of the solvent, providing a residue which was dissolved with a succinic acid solution and washed three times with 15 ml of dichloromethane. The washed aqueous phase was cooled, the pH adjusted to 12 with a 40% sodium hydroxide solution and extracted three times with 20 ml of dichloromethane. The combined organic phases were dried on anhydrous sodium sulphate and evaporated to dryness. The residue was recrystallised with isopropyl alcohol to give 780 mg (90%) of zolmitriptan as a white solid. (15-20 min.) It was left to cool to room temperature the reaction mixture filtered through decalite The filtrate was concentrated by vacuum distillation of the solvent providing a residue which washed three times with 15 ml of dichloromethane The washed aqueous phase was cooled extracted three times with 20 ml of dichloromethane The combined organic phases were dried on anhydrous sodium sulphate evaporated to dryness The residue was recrystallised with isopropyl alcohol

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

Procedure: A suspension of the product from step (c) (1.3 g) and 10% w/w Pd/C (1.0 g) in 30% w/w ethanolic dimethylamine (25 ml) was hydrogenated for 24 hours and filtered through Hyflo. Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours. The mixture was filtered through a silica column using DCM/EtOH/NH4OH (40:8:1) as eluant to give the desired product as a colourless foam (0.3 g). Elemental analysis and 1H NMR were consistent with the proposed structure. filtered through Hyflo Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours The mixture was filtered through a silica column

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

Procedure: By steps identical to steps (d) to (f) of Synthetic Example 1 and Synthetic Example 2 or steps (d) and (e) of Synthetic Example 1 and Synthetic Example 3 and steps (e) to (h) of Synthetic Example 4, the product from step (a) was converted to (S)-N,N-dimethyl-2-[5-(2-oxo-l,3-oxazolidin-4-ylmethyl)-1H. indol-3-yl]ethylamine.

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

Procedure: A suspension of the product from step (c) (1.3 g) and 10% w/w Pd/C (1.0 g) in 30% w/w ethanolic dimethylamine (25 ml) was hydrogenated for 24 hours and filtered through Hyflo. Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours. The mixture was filtered through a silica column using DCM/EtOH/NH4OH (40:8:1) as eluant to give the desired product as a colourless foam (0.3 g). Elemental analysis and 1H NMR were consistent with the proposed structure. filtered through Hyflo Fresh Pd/C (0.7 g) and ethanolic dimethylamine (5 ml) were added to the filtrate and hydrogenation continued for a further 16 hours The mixture was filtered through a silica column