4-methylpiperazin-1-amine

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:

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

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Part F: To a stirred solution of 49 mg (0.10 mmol) of 1-(2,4,6-trichlorophenyl)-3-isopropyl-6-(4-(carboxy)benzyl)pyrazolo[3,4-d]pyrimidin-4-one and 0.06 mL(0.5 mmol) of 1-amino-4-methylpiperazine in 1 mL of DMF was added 0.052 mL of DIEA followed by 48 mg (0.15 mmol) of TBTU. The solution was stirred 16 h at 45° C., cooled to RT, and poured into water. The mixture was extracted with EtOAc, and the organic extract was concentrated under reduced pressure. Chromatography with 4:1 chloroform-MeOH afforded 34 mg (58%) of 1-(2,4,6-trichlorophenyl)-3-isopropyl-6-(4-(4-methylpiperazin-1-ylaminocarbonyl)benzyl)pyrazolo[3,4-d]pyrimidin-4-on as a white solid. Mass spec: (ESI+) 588(M+H)+. cooled to RT The mixture was extracted with EtOAc the organic extract was concentrated under reduced pressure

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

Procedure: A mixture of 5.5 gm (0.0202 mol) of 5-chlorocarbonyl-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one, 8.6 gm (0.075 mol) of 1-amino-4-methylpiperazine, and 200 ml of anhydrous dioxane was heated for 30 minutes over a steam bath. Then, 2 gm of active charcoal were added to the resulting cloudy reaction mixture while it was still hot, the mixture was filtered, and the filtrate obtained was concentrated by evaporation in vacuo. The residue was purified by column chromatography on 300 gm of silica gel [eluant: dichloromethane/methanol/conc. aqueous ammonia mixture (volume ratio of 800:200:5)]. The residue remaining after the eluates had been concentrated was taken up in 500 ml of ethyl acetate, 1 gm of active charcoal was added, and the resulting mixture was boiled, filtered, and concentrated by evaporation. Then, 300 ml of methanol were added, and the resulting mixture was filtered while hot and evaporated to dryness. After recrystallization from ethanol, 1.8 gm (25% of theory) of colorless crystals were obtained, m.p.: 213°-214° C. (D). was heated for 30 minutes over a steam bath the mixture was filtered the filtrate obtained was concentrated by evaporation in vacuo The residue was purified by column chromatography on 300 gm of silica gel [eluant: dichloromethane/methanol/conc. aqueous ammonia mixture (volume ratio of 800:200:5)] had been concentrated 1 gm of active charcoal was added filtered concentrated by evaporation Then, 300 ml of methanol were added the resulting mixture was filtered while hot and evaporated to dryness After recrystallization from ethanol, 1.8 gm (25% of theory) of colorless crystals were obtained