5,6-dichloro-1H-indole

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

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

Procedure: 5,6-Dichloroindole (D38) was reduced in the usual way with sodium cyanoborohydride in glacial acetic acid to give the title compound (D39) (1.18 g, 90%).

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

Procedure: Beginning with 0.136 gm (0.88 mMol) 5,6-dichloro-1H-indole and 0.216 mL (1.75 mMol) 1-methyl-4-piperidone, 0.150 gm (61%) of the title compound were recovered as a white solid.

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

Procedure: Beginning with 0.136 gm (0.88 mMol) 5,6-dichloro-1H-indole and 0.216 mL (1.75 mMol) 1-methyl-4-piperidone, 0.150 gm (61%) of the title compound were recovered as a white solid.

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

Procedure: To a mixture of 5,6-dichloro-1H-indole (1.0 g, 5.37 mmol), Cu(OTf)2 (194 mg, 0.537 mmol) in DCM (15 mL) at RT, ethyl 2-diazoacetate (918 mg, 8.05 mmol) was added dropwise. The resulting mixture was stirred at RT for 16 h, quenched with water, and then extracted dichloromethane. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by Prep-HPLC to afford the desired product (120 mg, 8.2% yield) as light yellow solid. ESI-MS m/z: 272.1[M+H]+. quenched with water The organic layer was dried over Na2SO4 filtered concentrated in vacuo The residue was purified by Prep-HPLC

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

Procedure: 5,6-Dichloroindole (D38) was reduced in the usual way with sodium cyanoborohydride in glacial acetic acid to give the title compound (D39) (1.18 g, 90%).

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

Procedure: 5,6-Dichloroindole (D38) was reduced in the usual way with sodium cyanoborohydride in glacial acetic acid to give the title compound (D39) (1.18 g, 90%).

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

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 19.6 kg of 37% aqueous formaldehyde solution and 16.3 kg of DMF were added to a reactor and then the reactor was cooled to 5° C. 33.3 kg of 33% aqueous dimethylamine solution was added. The reaction mixture was stirred for an additional hour at 0-5° C. upon completion of addition. 11.8 kg of concentrated sulfuric acid was added slowly to the mixture while the temperature was maintained below 10° C. The mixture was stirred for an additional 15 minutes and cooled to 5° C. A solution of 30 kg of 5,6-dichloroindole in 30 kg of DMF was added slowly to the reactor and stirred for an additional hour at 5° C. The mixture was allowed to warm to room temperature and stirred for 24 hrs. The mixture was then added to a reactor containing a solution of 50 kg industrial sodium chloride in 1600 L water. To this reactor was added 10 kg activated carbon and the mixture stirred for 30 minutes. Upon filtration, the filtrate was adjusted to pH>12 with 20% aqueous sodium hydroxide solution. The precipitate was filtered, washed with water until pH=7-8, centrifuged, and dried to yield crude 35 kg 5,6-dichlorogramine. Recrystallization in 70% ethanol produced the pure product with melting point of 150-154° C. was maintained below 10° C The mixture was stirred for an additional 15 minutes cooled to 5° C stirred for an additional hour at 5° C to warm to room temperature stirred for 24 hrs The mixture was then added to a reactor To this reactor was added 10 kg the mixture stirred for 30 minutes Upon filtration The precipitate was filtered washed with water until pH=7-8 centrifuged, and dried

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Next, 37% aqueous formaldehyde solution and DMF are added into a reactor. The reactor is cooled to 0-5° C. and 33% aqueous dimethylamine solution then is added slowly with stirring. Concentrated sulfuric acid is added slowly to the mixture while the temperature is maintained at below 10° C. The mixture is stirred for an additional 15 minutes and cooled to 0-5° C. A solution of 5,6-dichloroindole (C) in DMF is added slowly to the reactor and stirred for an additional hour at 0-5° C. The mixture is allowed to warm to room temperature and stirred for 24 hrs. The mixture is then added to a reactor containing a solution of industrial sodium chloride in water. Activated carbon next is added and the mixture stirred for 30 minutes. Upon filtration, the filtrate is adjusted to pH>12 with 20% aqueous sodium hydroxide solution. The precipitate is filtered, washed with water until pH=7-8, centrifuged, and dried to yield crude 5,6-dichlorogramine (D). Recrystallization in 70% ethanol produces the pure product with melting point of 150-154° C. is maintained at below 10° C The mixture is stirred for an additional 15 minutes cooled to 0-5° C stirred for an additional hour at 0-5° C to warm to room temperature stirred for 24 hrs The mixture is then added to a reactor Activated carbon next is added the mixture stirred for 30 minutes Upon filtration The precipitate is filtered washed with water until pH=7-8 centrifuged, and dried

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

Procedure: Beginning with 0.136 gm (0.88 mMol) 5,6-dichloro-1H-indole and 0.216 mL (1.75 mMol) 1-methyl-4-piperidone, 0.150 gm (61%) of the title compound were recovered as a white solid.

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

Procedure: Beginning with 0.136 gm (0.88 mMol) 5,6-dichloro-1H-indole and 0.216 mL (1.75 mMol) 1-methyl-4-piperidone, 0.150 gm (61%) of the title compound were recovered as a white solid.