N,N-dimethylhydroxylamine

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: To a solution of Imidazo[1,2-a]pyridine-7-carboxylic acid methyl ester (0.67 g, 3.83 mmol) and dimethylhydroxylamine (0.93 g, 9.57 mmol) in CH2Cl2 (40 ml) at 0° C. was added 2M trimethylaluminium solution in hexane (3.8 ml, 9.57 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 1 h, before being cooled back to 0° C. and quenched with ice. The reaction was filtered and liquid fraction partitioned between CH2Cl2/H2O. The organic layer was separated, dried (MgSO4), filtered and the solvent removed in vacuo to afford the crude product. The residue was purified by silica column chromatography (0-50% MeOH in Et2O) to afford the product (187 mg). MS: [M+H]+=206. before being cooled back to 0° C. quenched with ice The reaction was filtered liquid fraction partitioned between CH2Cl2/H2O The organic layer was separated dried (MgSO4) filtered the solvent removed in vacuo to afford the crude product The residue was purified by silica column chromatography (0-50% MeOH in Et2O)

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

Conditions: temp:-12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Benzyloxy-7-morpholin-4-yl-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carboxylic acid (product of example 5, 100 mg, 0.263 mmol) was dissolved in THF (1 mL) and DCM (11 mL) and cooled to −20° C. N-Methylmorpholine (30 μL, 0.265 mmol) was added and the temperature was raised to −12° C. Ethyl chloroformate was added and after 2 minutes, the solution of dimethylhydroxylamine. The reaction was warmed to room temperature and stirred for one hour. After this time, the mixture was quenched by addition of 0.2 M HCl. The layers were separated and the organic layer was washed sequentially with 0.2 M HCl, 0.5 M NaOH (2×) and brine. Then dried and concentrated. The product was isolated as a yellow solid (112 mg, 100% yield) and was used without further purification. The reaction was warmed to room temperature After this time, the mixture was quenched by addition of 0.2 M HCl The layers were separated the organic layer was washed sequentially with 0.2 M HCl, 0.5 M NaOH (2×) and brine Then dried concentrated

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

Procedure: In the manner given in Example 2, a solution of N,N-dimethylhydroxylamine in dimethylformamide is treated with sodium hydride, suspended in mineral oil, and the mixture is treated with 8-nitro-1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine to give 8-nitro-1-[(dimethylamino)methyl]-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine, N1 -oxide.

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

Procedure: In the manner given in Example 2, a solution of N,N-dimethylhydroxylamine in dimethylformamide is treated with sodium hydride suspended in mineral oil, and the mixture is treated with 8-fluoro-1-(bromomethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine to give 8-fluoro-1-[(dimethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, N1 -oxide.

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

Procedure: In the manner given in Example 2, a solution of N,N-dimethylhydroxylamine in dimethylformamide is treated with sodium hydride suspended in mineral oil, and the mixture is treated with 8-fluoro-1-(bromomethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine to give 8-fluoro-1-[(dimethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, N1 -oxide.

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

Procedure: A stirred solution of N,N-dimethylhydroxylamine (3.67 g, 0.06 mole) in dry dimethylformamide (50 ml) is cooled in an ice bath, under nitrogen, and treated with a 57% mineral oil suspension of sodium hydride (0.84 g, 0.02 mole). The mixture is kept at ambient temperature for 1 hour (a precipitate formed) and then cooled in an ice bath and treated with 8-chloro-1-(chloromethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepine (6.86 g, 0.02 mole). The mixture is kept at ambient temperature for 2 hours and concentrated in vacuo. Last traces of dimethylformamide are removed from the residue by the successive addition and distillation with xylene, toluene, and benzene. The resulting material is chromatographed on silica gel (250 g) with methanol. The product thus obtained is crystallized from methanol-ethyl acetate (following activated charcoal treatment) to give 8-chloro-1-[(dimethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, N1 -oxide, hydrate in three crops: 3.377 g of melting point 160.5°-162.5° C.; 1.145 g of melting point 160°-162° C.; and 0.785 g of melting point 160°-162° C. The analytical sample had a melting point of 157.5°-158.5° C. with decomposition. (a precipitate formed) and then cooled in an ice bath The mixture is kept at ambient temperature for 2 hours concentrated in vacuo Last traces of dimethylformamide are removed from the residue by the successive addition and distillation with xylene, toluene, and benzene The resulting material is chromatographed on silica gel (250 g) with methanol The product thus obtained is crystallized from methanol-ethyl acetate (following activated charcoal treatment)

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

Procedure: A stirred solution of N,N-dimethylhydroxylamine (3.67 g, 0.06 mole) in dry dimethylformamide (50 ml) is cooled in an ice bath, under nitrogen, and treated with a 57% mineral oil suspension of sodium hydride (0.84 g, 0.02 mole). The mixture is kept at ambient temperature for 1 hour (a precipitate formed) and then cooled in an ice bath and treated with 8-chloro-1-(chloromethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepine (6.86 g, 0.02 mole). The mixture is kept at ambient temperature for 2 hours and concentrated in vacuo. Last traces of dimethylformamide are removed from the residue by the successive addition and distillation with xylene, toluene, and benzene. The resulting material is chromatographed on silica gel (250 g) with methanol. The product thus obtained is crystallized from methanol-ethyl acetate (following activated charcoal treatment) to give 8-chloro-1-[(dimethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, N1 -oxide, hydrate in three crops: 3.377 g of melting point 160.5°-162.5° C.; 1.145 g of melting point 160°-162° C.; and 0.785 g of melting point 160°-162° C. The analytical sample had a melting point of 157.5°-158.5° C. with decomposition. (a precipitate formed) and then cooled in an ice bath The mixture is kept at ambient temperature for 2 hours concentrated in vacuo Last traces of dimethylformamide are removed from the residue by the successive addition and distillation with xylene, toluene, and benzene The resulting material is chromatographed on silica gel (250 g) with methanol The product thus obtained is crystallized from methanol-ethyl acetate (following activated charcoal treatment)