1-[benzyl-[2-(2-methoxyphenoxy)ethyl]amino]-3-(9H-carbazol-4-yloxy)propan-2-ol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:47.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzyl carvedilol (205 g) obtained in step 3 was charged to ethyl acetate (2400 ml) and water (240 ml). The contents were stirred and 10% palladium on carbon (20 g) was added at room temperature. Hydrogen gas was bubbled at room temperature. The temperature was raised to 45-50° C. and bubbling was continued for 8 hours. The reaction mass was filtered to remove the catalyst and the filtrate was concentrated to remove solvent (about 2 L). The contents were chilled to 15-20° C., filtered and washed with chilled ethyl acetate (50 ml) to give carvedilol (140 g) (84%). Hydrogen gas was bubbled at room temperature bubbling The reaction mass was filtered to remove the catalyst the filtrate was concentrated to remove solvent (about 2 L) The contents were chilled to 15-20° C. filtered washed with chilled ethyl acetate (50 ml)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g of 1-{Benzyl-[2-(2-methoxy-phenoxy)-ethyl]-amino}-3-(9H-carbazol-4-yloxy)-propan-2-ol (20 mmol) were dissolved in 80 ml methanol. 1 g of Pd—C (10%) were added and the suspension was warmed to 50° C. The mixture was hydrogenated at normal pressure for about 7 hours. The Pd-catalyst was filtered under suction and washed with 25 ml of hot methanol. 80 ml of methanol were distilled off and the residue was cooled to 0° C. and hold at this temperature for 6 h. The product was filtered and washed twice with 3 ml cold methanol. The substance was dried at 60° C. for 12 h. The Pd-catalyst was filtered under suction washed with 25 ml of hot methanol 80 ml of methanol were distilled off the residue was cooled to 0° C. hold at this temperature for 6 h The product was filtered washed twice with 3 ml cold methanol The substance was dried at 60° C. for 12 h.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 35.0 g of benzyl-[2-(2-methoxy-phenoxy)-ethyl]-amine (136 mmol) were dissolved in 225 ml ethanol. To the stirred solution 30.1 g of 4-oxiranylmethoxy-9H-carbazole (126 mmol) were added and the mixture was heated under reflux for 15 h. The boiling solution was treated with 3 g of activated carbon for 30 min. The activated carbon was filtered off in the heat, and washed with 20 ml ethanol. The solution was stirred for 3 h at room temperature and next 5 h at 0° C. The product was filtered under suction and washed twice with 10 ml cold ethanol. The substance was dried at 50° C. for 12 h the mixture was heated under reflux for 15 h The boiling solution was treated with 3 g of activated carbon for 30 min The activated carbon was filtered off in the heat washed with 20 ml ethanol The product was filtered under suction washed twice with 10 ml cold ethanol The substance was dried at 50° C. for 12 h

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.3 g of 1-(9-Benzenesulfonyl-9H-carbazol-4-yloxy)-3-{benzyl-[2-(2-methoxyphenoxy)-ethyl]-amino}-propan-2-ol (5.2 mmol) were dissolved in 33 ml THF/methanol (2:1). A solution of 1.1 g of sodium hydroxide in 1.7 ml of water was added in one portion. The mixture was stirred for 18 h at 50° C. The mixture was rotary evaporated (35° C./20 mbar). The residue was dissolved in 25 ml of toluene and 20 ml of water. The phases were separated and the toluene phase was washed 3 times with 25 ml of water. The organic phase was rotary evaporated (40° C./15 mbar) and the residue was crystallized with 9 ml ethanol. The product was filtered under suction and washed twice with 3 ml cold ethanol. The substance was dried at 50° C. for 12 h. The mixture was rotary evaporated (35° C./20 mbar) The residue was dissolved in 25 ml of toluene The phases were separated the toluene phase was washed 3 times with 25 ml of water The organic phase was rotary evaporated (40° C./15 mbar) the residue was crystallized with 9 ml ethanol The product was filtered under suction washed twice with 3 ml cold ethanol The substance was dried at 50° C. for 12 h.

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

Procedure: reaction of 4-oxiranylmethoxy-9H-carbazole with benzyl-[2-(2-methoxy-phenoxy]-ethylamine to give a 1-{benzyl-[2-(2-methoxy-phenoxy)-ethyl]-amino}-3-(9H-carbazol-4-yloxy)propan-2-ol;