2-bromoacetaldehyde

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:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-amino-1-ethyl)-4-(1,4-benzodioxan-5-yl)piperazine (9.1 g), bromoacetaldehyde dimethylacetale (6.5 g), potassium iodide (0.5 g), and potassium carbonate (4.8 g) in 1,4-dioxan (200 ml) was refluxed for 16 h. Water was added followed by extraction with ethyl acetate. The organic phase was concentrated in vacuo leaving an oil which was applied to a silica gel column (eluent: ethyl acetate/methanol=1:3). The product, 1-(1,4-benzodioxan-5-yl)-4-[2-(2,2-dimethoxy-1-ethylamino)-1-ethyl]piperazine, was obtained as an oil (4.7 g). was refluxed for 16 h followed by extraction with ethyl acetate The organic phase was concentrated in vacuo leaving an oil which

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

Procedure: In the manner given in Example 1, 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine can be reacted with α-bromoacetaldehyde to give 7-chloro-2-[(2-bromoethylidene)hydrazino]-5-phenyl-3H-1,4-benzodiazepine.

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (S)-6-(3-amino-propyl)-6-aza-spiro[2.5]octan-4-ol (200 mg, 1.09 mmol), bromoacetaldehyde (183 mg, 1.09 mmol), potassium carbonate (300 mg, 2.17 mmol), and EtOH (2.5 mL) was heated at 150° C. for 20 min under microwave irradiation, then insoluble material was removed by filtration and the filtrate evaporated to afford 224 mg of a 60:40 mixture of the title compound and the tertiary amine (S)-6-{3-[bis-(2,2-dimethoxy-ethyl)-amino]-propyl}-6-aza-spiro[2.5]octan-4-ol, which was directly used in the next step. Yellow gum, MS: 273.2 (M+H)+. insoluble material was removed by filtration the filtrate evaporated to afford

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (S)-6-(3-amino-propyl)-6-aza-spiro[2.5]octan-4-ol (200 mg, 1.09 mmol), bromoacetaldehyde (183 mg, 1.09 mmol), potassium carbonate (300 mg, 2.17 mmol), and EtOH (2.5 mL) was heated at 150° C. for 20 min under microwave irradiation, then insoluble material was removed by filtration and the filtrate evaporated to afford 224 mg of a 60:40 mixture of the title compound and the tertiary amine (S)-6-{3-[bis-(2,2-dimethoxy-ethyl)-amino]-propyl}-6-aza-spiro[2.5]octan-4-ol, which was directly used in the next step. Yellow gum, MS: 273.2 (M+H)+. insoluble material was removed by filtration the filtrate evaporated to afford

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium methylate (18.1 g) is added in portions to a solution of 1-methylpiperidine-4-thiol (22 g) in anhydrous tetrahydrofuran (200 ml). After one hour, the diethyl acetal of bromoacetaldehyde (30.3 ml) is added. After 4 hours at room temperature, the solution is heated for 2 hours at 40° C. The insoluble material is filtered off and rinsed with THF. The filtrate is concentrated and then distilled under reduced pressure to give 4-[(2,2-diethoxyethyl)thio]-1-methylpiperidine (36 g; b.p.=104°-108° C. under 0.05 atm) in the form of an oil. After 4 hours at room temperature The insoluble material is filtered off rinsed with THF The filtrate is concentrated distilled under reduced pressure

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

Procedure: 1,1-Dipropylprop-2-ynylamine (1.6 mole), the diethyl acetal of 2-bromoacetaldehyde (1.0 mole) and methanol (100 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux with stirring for a period of about 6 hours. After this time the reaction mixture is cooled to room temperature and sodium hydroxide (20 grams) is added. The reaction mixture is then stirred for an additional period of about 16 hours. The mixture is then filtered and the filtrate is distilled to yield the desired product the diethyl acetal of 2-(1,1-dipropylprop-2-ynylamino)acetaldehyde. equipped with a mechanical stirrer thermometer and reflux condenser The reaction mixture is heated at reflux The reaction mixture is then stirred for an additional period of about 16 hours The mixture is then filtered the filtrate is distilled

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

Procedure: 1,1-Dimethylprop-2-ynylamine (2.0 mole), the diethyl acetal of 2-bromoacetaldehyde (1.0 mole) and methanol (100 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux with stirring for a period of about 6 hours. After this time the reaction mixture is cooled to room temperature and sodium hydroxide (20 grams) is added. The reaction mixture is then stirred for an additional period of about 16 hours. The mixture is then filtered and the filtrate is distilled to yield the desired product the diethyl acetal of 2-(1,1-dimethylprop-2-ynylamino)acetaldehyde. equipped with a mechanical stirrer thermometer and reflux condenser The reaction mixture is heated at reflux The reaction mixture is then stirred for an additional period of about 16 hours The mixture is then filtered the filtrate is distilled

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

Procedure: Hex-4-enylamine (2.0 mole), the diethyl acetal of 2-bromoacetaldehyde (1.0 mole) and methanol (100 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at reflux with stirring for a period of about 6 hours. After this time the reaction mixture is cooled to room temperature and sodium hydroxide (20 grams) is added. The reaction mixture is then stirred for an additional period of about 16 hours. The mixture is then filtered and the filtrate is distilled to yield the desired product the diethyl acetal of 2-hex-4-enylaminoacetaldehyde. equipped with a mechanical stirrer thermometer and reflux condenser The reaction mixture is heated at reflux The reaction mixture is then stirred for an additional period of about 16 hours The mixture is then filtered the filtrate is distilled