3-(4-methylpiperazin-1-yl)propan-1-ol

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:6.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.7 g (61.2 mmol) of N-methyl-N′-(3-hydroxypropyl)piperazine dissolved in 10 ml of acetonitrile are added dropwise to a solution of 100 ml of acetonitrile and 40 ml of 4 N HCl in dioxane and cooled using a water bath that the internal temperature did not exceed 40° C. 8 ml (66.3 mmol) of trichloromethyl chloroformate in 10 ml of acetonitrile are subsequently added dropwise with ice-cooling at an internal temperature of 2-10° C., and the mixture is subsequently stirred at room temperature for 15 h. The precipitate formed is filtered off with suction, washed with acetonitrile, and the residue is dried in vacuo. cooled did not exceed 40° C The precipitate formed is filtered off with suction washed with acetonitrile the residue is dried in vacuo

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of diisopropyl azodicarboxylate (12.1 ml) in methylene chloride (50 ml) was added dropwise during 30 minutes to a stirred mixture of 4-chloro-3-cyano-7-hydroxy-6-methoxyquinoline (12 g), 1-(3-hydroxypropyl)-4-methylpiperazine (9.7 g), triphenylphosphine (16.1 g) and methylene chloride (200 ml) that had been cooled to 5° C. The resultant mixture was allowed to warm to ambient temperature and was then stirred for 1 hour. Further portions of diisopropyl azodicarboxylate (1.2 ml) and triphenylphosphine (1.6 g) were added and the mixture was stirred at ambient temperature for a further 1 hour. The mixture was poured into water and the organic layer was separated, washed with a saturated brine solution, dried over magnesium sulphate and evaporated. The material so obtained was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent. There was thus obtained the required starting material as a solid (14.5 g); NMR Spectrum: (DMSOd6) 1.95 (m, 2H), 2.13 (s, 3H), 2.24–2.5 (m, 10H), 4.0 (s, 3H), 4.25 (t, 2H), 7.43 (s, 1H), 7.51 (s, 1H), 8.95 (s, 1H); Mass Spectrum: M+H+ 375 and 377. to warm to ambient temperature the mixture was stirred at ambient temperature for a further 1 hour the organic layer was separated washed with a saturated brine solution dried over magnesium sulphate evaporated The material so obtained was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent There was thus obtained the

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

Procedure: A mixture of 3-bromopropanol (20 ml), N-methylpiperazine (29 ml), potassium carbonate (83 g) and ethanol (200 ml) was stirred and heated to reflux for 20 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The resultant mixture was filtered and the filtrate was evaporated. The residue was purified by distillation at about 60–70° C. under about 0.2 mm Hg to give 1-(3-hydroxypropyl)-4-methylpiperazine (17 g); NMR Spectrum: (CDCl3) 1.72 (m, 2H), 2.3 (s, 3H), 2.2–2.8 (m, 8H), 2.6 (t, 2H), 3.8 (t, 2H), 5.3 (br s, 1H). heated to reflux for 20 hours filtered The filtrate was evaporated the residue was triturated under diethyl ether The resultant mixture was filtered the filtrate was evaporated The residue was purified by distillation at about 60–70° C. under about 0.2 mm Hg

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

Procedure: To a solution of 4-fluoro-2-(methyloxy)-1-nitrobenzene (1 g, 5.8 mmol) in 20 mL of anhydrous DMF was added 3-(4-methyl-1-piperazinyl)-1-propanol (1.2 g, 7.59 mmol). Sodium hydride (60%) (467 mg, 11.68 mmol) was added portionwise and the reaction was stirred at rt for 90 min at which time it was quenched with a solution of saturated NH4Cl (5 mL) and most of the DMF was removed under reduced pressure. The residue was diluted with ethyl acetate and washed with a minimum amount of water and a saturated sodium chloride solution, dried over Na2SO4 and filtered. Solvents were removed under reduced pressure to give 1-methyl-4-(3-{[3-(methyloxy)-4-nitrophenyl]oxy}propyl)piperazine as a yellow solid (1.8 g total isolated, some residual DMF in product) (ESIMS (M+H)+=311) was quenched with a solution of saturated NH4Cl (5 mL) and most of the DMF was removed under reduced pressure The residue was diluted with ethyl acetate washed with a minimum amount of water a saturated sodium chloride solution, dried over Na2SO4 filtered Solvents were removed under reduced pressure