alentamol

alentamol Chemische Eigenschaften,Einsatz,Produktion Methoden

• Originator

  U 68553B ,Upjohn Company

• Manufacturing Process

  The solid 5-methoxy-2,2-dicarboxy-2,3-dihydro-1H-phenalene, was decarboxylated (one carboxyl group removed) by heating in an oil bath at 190°-210°C for 50 min. The resulting liquid was cooled, and the solid was ground to a fine powder to obtain 37.1 g (98% yield) of the subtitled 2- carboxyl-5-methoxy-2,3-dihydro-1H-phenalene, melting point 194°-196°C.
  A mixture of the 5-methoxy-2,3-dihydro-1H-phenalen-2-yl-carboxylic acid, (37.1 g; 0.153 mole), 42.1 g (0.153 mole) of diphenyl phosphoryl azide, 17.0 g (0.168 mole) of triethylamine and 1950 ml of dry tert-butyl alcohol was refluxed for 21 h. The initially formed solution became a suspension. The solvent was evaporated in vacuo and the residue was taken up in a chloroform/water mixture. The resulting suspension was filtered. The filtrate was separated, the aqueous phase was extracted with chloroform, and the combined organic liquid phases was washed with 5% w/v sodium hydroxide aqueous solution (3x100 ml), with water and with saturated sodium chloride salt solution and then dried over magnesium sulfate and evaporated.The resulting residual yellow solid, 35.9 g, was extracted with boiling SKELLYSOLVE B brand of hexanes (5x200 ml), the resulting solution was concentrated to about 300 ml, clarified with diethyl ether and allowed to crystallize at 0°C to obtain 28.6 g of the 5-methoxy-2-(tertbutoxycarbonylamino)- 2,3-dihydro-1H-phenalene, melting point 113°-115°C.
  Trifluoroacetic acid, 85 ml, was added to 30.5 g (0.0958 mole) of the 5- methoxy-2-(tert-butoxycarbonylamino)-2,3-dihydro-1H-phenalene. The resulting solution was stirred for 20 min. Ice was then added, and the resulting mixture was made pH basic with 20% w/w sodium hydroxide in water solution and stirred for 1 h at room temperature. The mixture was extracted well with chloroform, the chloroform extract was separated and washed with water, with saturated sodium chloride solution; dried with magnesium sulfate, and evaporated to give 18.8 g (92% yield) of the 2- amino-5-methoxy-2,3-dihydro-1H-phenalene as a brown oil.
  This 2-amino-5-methoxy-2,3-dihydro-1H-phenalene was converted to its hydrochloride salt in methanol with 1.5 N hydrogen chloride in diethyl ether solution to give 18.11 g of the 2-amino-5-methoxy-2,3-dihydro-1H-phenalene hydrochloride as colorless needle crystals, melting point 252°C (dec.).
  A mixture of 2-amino-5-methoxy-2,3-dihydro-1H-phenalene, 2.6 g (0.0122 mole), released from its hydrochloride, 6.46 g (0.0525 mole) of n-propylbromide, 7.25 g (0.0525 mole) of potassium carbonate and 50 ml of acetonitrile was refluxed for 20 h. Another 3.3 g of n-propyl bromide, 3.6 g of potassium carbonate and 25 ml of acetonitrile were added to the reaction mixture. The mixture was refluxed for 26 h. GC analysis of a sample of the reaction mixture indicated complete reaction. The mixture was evaporated, and the residue was taken up in a diethyl ether/water mixture. The organic liquid layer was washed with saturated sodium chloride (salt) solution and dried with magnesium sulfate, and evaporated. The residue was dissolved in petroleum ether (boiling point 30°-60°C), and filtered from some insoluble brown material, and the filtrate was evaporated to leave the 2-(di-npropylamino)- 5-methoxy-2,3-dihydro-1H-phenalene.
  The 2-(di-n-propylamino)-5-methoxy-2,3-dihydro-1H-phenalene was dissolved in diethyl ether, treated with ethereal hydrogen chloride which resulted in the formation of the crude gummy solid hydrogen chloride salt. 2.67 g (66% yield) of the 2-(di-n-propylamino)-5-methoxy-2,3-dihydro-1H-phenalene hydrochloride, melting point 196°-197°C (crystallized from a methanol/diethyl ether).
  A mixture of 2-(di-n-propylamino)-5-methoxy-2,3-dihydro-1H-phenalene, (1.65 g; 5.55 mmol), released from the hydrochloride salt, and 20 ml of 48% aqueous hydrogen bromide solution was heated for 15 min in an oil bath at 125°-130°C. The reaction mixture was evaporated, the residue was dissolved in a minimum amo

• Therapeutic Function

  Antipsychotic, Dopamine agonist

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