1-(2-chloroethyl)-4-methylpiperazine

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: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: The N′-methyl-N-2-chloroethylpiperazine dihydrochloride (10.0 g, 45.4 mmol) was added slowly to a mixture of 50% aqueous potassium carbonate (200 mL) and ether (200 mL) and the mixture was stirred for 30 min., layers were separated, aqueous layer extracted with ether (2×200 mL). Combined organic extracts were dried on anhydrous sodium sulfate and concentrated to give N′-methyl-N-2-chloroethylpiperazine (6.2 g). layers were separated aqueous layer extracted with ether (2×200 mL) Combined organic extracts were dried on anhydrous sodium sulfate concentrated

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

Procedure: In the manner given in Example 25, to 6,7-difluoro-2,9-dihydro-9-[ (dipropylamino)acetyl]-3H-pyrido[3,2-c]-s-triazolo[4,3-a][1,5]benzodiazepin-3-one in dimethylforamide is added a solution of sodium hydrided in mineral oil. The mixture is allowed to react at about 95°C. for 40 minutes and after cooling [2-(4-methylpiperazino)-ethyl]chloride in xylene is added. The mixture is kept at 95°-100° C. for a period of 22 hours, evaporated and worked up as in example 25 to give 6,7-difluoro-2.9-dihydro-2-[2-(4-methylpiperazino)ethyl]-9-[(dipropylamino)acetyl]-3H-pyrido[3,2-c]-s-triazolo[4,3-a][1,5]-benzodiazepin-3-one. to react at about 95°C. for 40 minutes is added evaporated

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

Procedure: The N′-methyl-N-2-chloroethylpiperazine dihydrochloride (10.0 g, 45.4 mmol) was added slowly to a mixture of 50% aqueous potassium carbonate (200 mL) and ether (200 mL) and the mixture was stirred for 30 min., layers were separated, aqueous layer extracted with ether ( 2×200 mL). Combined organic extracts were dried on anhydrous sodium sulfate and concentrated to give N′-methyl-N-2-chloroethylpiperazine (6.2 g). layers were separated aqueous layer extracted with ether ( 2×200 mL) Combined organic extracts were dried on anhydrous sodium sulfate concentrated

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

Procedure: N1 -β-chloroethyl-N4 -methylpiperazine, 1-n-butyl-3-[N1 -β-(N4 -methyl)-piperazinoethoxy]-4-phenyl-3-pyrrolin-2-one; dioxalate m.p. 199° C. 32.5 g. (0.14 mol) 1-n-butyl-3-hydroxy-4-phenyl-3-pyrrolin-2-one is added, with stirring, at 40° C. to a suspension of 4.2 g. sodium hydride (80%) in 200 ml. dimethyl formamide. When the evolution of hydrogen ceases, 30.0 g. N1 -β-chloroethyl-N4 -methylpiperazine is added and the mixture allowed to react for 30 minutes at 70° C. The mixture is immediately poured into 1.5 liters of ice water. This is then extracted twice with dichloromethane and the organic phase is washed with water. After drying over anhydrous magnesium sulphate, the solvent is distilled off. The residue (base) is taken up in diethyl ether and oxalic acid is added to precipitate out the di-oxalate. After recrystallization of this dioxalate from aqueous methanol, there is obtained 33.0 g. (44% of theory) of the desired end product. to react for 30 minutes at 70° C This is then extracted twice with dichloromethane the organic phase is washed with water After drying over anhydrous magnesium sulphate the solvent is distilled off oxalic acid is added to precipitate out the di-oxalate After recrystallization of this dioxalate from aqueous methanol there is obtained 33.0 g