4,4-diethoxy-N-methylbutan-1-amine

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

Procedure: The title compound was prepared by following General Methods 2, 3 and 4 using 4-chlorophenylhydrazine hydrochloride, propargyl bromide, and tetra-n-butylammonium chloride (General Method 2), 1-(4-chlorophenyl)-1-(prop-2-ynyl)hydrazine (Example 8) and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3) and 2-(5-chloro-1-(prop-2-ynyl)-1H-indol-3-yl)-N-methylethanamine (Example 17), formaldehyde and TFA in acetonitrile (General Method 4).

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

Procedure: The title compound is prepared by following General Methods 1, 3, 4, 5 and 7 by using 3-chlorophenylhydrazine hydrochloride, ethyl bromoacetate, and triethylamine (General Method 1), ethyl 2-(1-(3-chlorophenyl)hydrazinyl)acetate and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3), ethyl 2-(6-chloro-3-(2-(methylamino)ethyl)-1H-indol-1-yl)acetate, formaldehyde and TFA in acetonitrile (General Method 4), ethyl 2-(7-chloro-1,2,3,4-tetrahydro-2-methylpyrido[3,4-b]indol-9-yl)acetate and NaOH (General Method 5), and 2-(7-chloro-1,2,3,4-tetrahydro-2-methylpyrido[3,4-b]indol-9-yl)acetic acid, piperidine and EDCI (General Method 7).

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

Procedure: The title compound is prepared by following General Methods 1, 3, 4, 5 and 7 by using 4-chlorophenylhydrazine hydrochloride, ethyl 4-bromobutyrate, and triethylamine (General Method 1), ethyl 4-(1-(4-chlorophenyl)hydrazinyl)butanoate and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3), ethyl 4-(5-chloro-3-(2-(methylamino)ethyl)-1H-indol-1-yl)butanoate, formaldehyde and TFA in acetonitrile (General Method 4), ethyl 4-(6-chloro-1,2,3,4-tetrahydro-2-methylpyrido[3,4-b]indol-9-yl)butanoate and NaOH (General Method 5), and 4-(6-chloro-1,2,3,4-tetrahydro-2-methylpyrido[3,4-b]indol-9-yl)butanoic acid, piperidine and EDCI (General Method 7).

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-[N-(4-Chloro-phenyl)-hydrazino]-1-(methyl-piperidin-1-yl)-ethanone (0.75 g, 2.66 mmol) was dissolved in ethyl acetate (3 mL) and 4M hydrochloride in dioxane (0.7 mL) was added. The mixture was concentrated under reduced pressure to a glassy oil/foam. This was dissolved in a mixture of ethanol (4 mL) and water (2 mL) and heated to 60° C. The 4,4-diethoxy-N-methylbutan-1-amine (0.47 g, 2.68 mmol) was added and then heated to 7080° C. 28% aqueous HCl (0.35 mL, 2.66 mmol) was added and the reaction heated at 80° C. for 1 h. More 4,4-diethoxy-N-methylbutan-1-amine (0.2 g, 1.14 mmol) and 28% aqueous HCl (0.3 mL, 2.30 mmol) was added and heated for a further 3 h. Further 4,4-diethoxy-N-methylbutan-1-amine (0.3 g, 1.71 mmol) was added and heated for a further 6 h. The reaction was concentrated under reduced pressure to give a dark brown oil. The oil was subjected to column chromatography (silica gel, eluent: EtOAc:EtOH:NH4OH 7:3:1) to give a brown oil (0.29 g). Further purification of the brown oil by column chromatography (silica gel, eluent: EtOAc:EtOH:NH4OH 7:3:1) gave pure product (179 mg, 19%). The mixture was concentrated under reduced pressure to a glassy oil/foam This was dissolved in a mixture of ethanol (4 mL) and water (2 mL) heated to 7080° C the reaction heated at 80° C. for 1 h heated for a further 3 h heated for a further 6 h The reaction was concentrated under reduced pressure to give a dark brown oil

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

Procedure: The title compound is prepared by following General Methods 1, 3, and 4 by using 4-chlorophenylhydrazine hydrochloride, 1-(N-bromoacetyl)-4-methyl piperidine, and triethylamine (General Method 1), 2-(1-(4-chlorophenyl)hydrazinyl)-1-(4-methylpiperidin-1-yl)ethanone and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3), 2-(5-chloro-3-(2-(methylamino)ethyl)-1H-indol-1-yl)-1-(4-methylpiperidin-1-yl)ethanone, formaldehyde and TFA in acetonitrile (General Method 4).

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

Procedure: The title compound is prepared by following General Methods 1, 3 and 4 using 4-chlorophenylhydrazine hydrochloride, tert-butyl 4-(2-bromoethyl)piperazine-1-carboxylate, and triethylamine (General Method 1), N-Boc-1-(4-chlorophenyl)-1-(2-(piperazin-1-yl)ethyl)hydrazine and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3), tert-butyl 4-(2-(5-chloro-3-(2-(methylamino)ethyl)-1H-indol-1-yl)ethyl)piperazine-1-carboxylate, formaldehyde and TFA in acetonitrile (General Method 4), and Boc deprotection by using TFA/dichloromethane.

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

Procedure: The title compound is prepared by following General Methods 1, 3 and 4 using 4-chlorophenylhydrazine hydrochloride, 3-(2-bromoethyl)-1,1-dimethylcyclopentane, and triethylamine (General Method 1), 1-(4-chlorophenyl)-1-(2-(3,3-dimethylcyclopentyl)ethyl)hydrazine and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3) and 2-(5-chloro-1-(2-(3,3-dimethylcyclopentyl)ethyl)-1H-indol-3-yl)-N-methylethanamine (Example 14), formaldehyde and TFA in acetonitrile (General Method 4).

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 28% aqueous HCl (0.3 mL, 2.26 mmol) was added to a solution of N-(4-Chloro-phenyl)-N-(2-cyclopentyl-ethyl)-hydrazine (0.54 g, 2.26 mmol) in ethanol (2.5 mL) and water (1 mL) under a nitrogen atmosphere. The reaction was heated to 60° C. (oil bath temperature) and 4,4-diethoxy-N-methylbutan-1-amine (0.32 g, 1.84 mmol) was added. The reaction was heated to reflux and 28% aqueous HCl (0.15 mL, 1.13 mmol) was added. The reaction was heated at reflux for 2.5 h. The reaction was cooled to 60° C. and then more 4,4-diethoxy-N-methylbutan-1-amine (0.32 g, 1.84 mmol) was added. The reaction was heated to reflux and then more 28% aqueous HCl (0.15 mL, 1.13 mmol) was added. The reaction was heated to reflux for a further 3.5 h. The reaction was cooled and concentrated under reduced pressure. The red brown residue was subjected to column chromatography (silica gel, eluent: EtOAc followed by EtOAc:EtOH:NH4OH 90:10:1) to give the product (0.318 g, 46%). was added The reaction was heated to reflux The reaction was heated at reflux for 2.5 h The reaction was heated to reflux The reaction was heated to reflux for a further 3.5 h The reaction was cooled concentrated under reduced pressure

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

Procedure: The title compound was prepared by following General Methods 2, 3 and 4 using 4-chlorophenylhydrazine hydrochloride, 1-(2-chloroethyl)piperidine hydrochloride, and tetra-n-butylammonium chloride (General Method 2), 1-(4-chlorophenyl)-1-(2-(piperidin-1-yl)ethyl)hydrazine (Example 3) and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3) and 2-(5-chloro-1-(2-(piperidin-1-yl)ethyl)-1H-indol-3-yl)-N-methylethanamine (Example 12), formaldehyde and TFA in acetonitrile (General Method 4).

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

Procedure: The title compound is prepared by following General Methods 1, 3 and 4 using 4-chlorophenylhydrazine hydrochloride, 5-(3-bromopropyl)-2-methylpyridine, and triethylamine (General Method 1), 1-(3-(6-methylpyridin-3-yl)propyl)-1-p-tolylhydrazine and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3) and N-methyl-2-(5-methyl-1-(3-(6-methylpyridin-3-yl)propyl)-1H-indol-3-yl)ethanamine, formaldehyde and TFA in acetonitrile (General Method 4).

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

Procedure: The title compound is prepared by following General Methods 1, 3 and 4 using 4-chlorophenylhydrazine hydrochloride, 1-(3-bromopropyl)-4-fluorobenzene, and triethylamine (General Method 1), 1-(4-chlorophenyl)-1-(3-(4-fluorophenyl)propyl)hydrazine and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3) and 2-(5-chloro-1-(3-(4-fluorophenyl)propyl)-1H-indol-3-yl)-N-methylethanamine, formaldehyde and TFA in acetonitrile (General Method 4).

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

Procedure: The title compound is prepared by following General Methods 1, 3 and 4 using 4-chlorophenylhydrazine hydrochloride, 3-(3-bromopropyl)pyridine, and triethylamine (General Method 1), 1-(4-chlorophenyl)-1-(3-(pyridin-3-yl)propyl)hydrazine and 4,4-diethoxy-N-methylbutan-1-amine (General Method 3) and 2-(5-chloro-1-(3-(pyridin-3-yl)propyl)-1H-indol-3-yl)-N-methylethanamine, formaldehyde and TFA in acetonitrile (General Method 4).