Apaxifylline

Originator

Apaxifylline,Boehringer Ingelheim/Upjohn

Uses

Selective adenosine A1antagonist.

Manufacturing Process

1,3-Dipropyl-8-(3-oxocyclopentyl)xanthyne:
1). 100 g 3-oxocyclopentancarboxylic acid methyl ester (0.7 moles) was heated with 1000 ml of 2 M hydrochloric acid to reflux for 10 hours. On cooling the solution was evaporated in vacuum. Residual water was removed by azeotropic dehydratation. The residue was distilled in high vacuum to give 3-oxocyclopentancarboxylic acid as colorless oil, b.p.: 116°-121°C/0.002 mm; yield 74.0 g (82 %).
2). 11.6 g carbonyl diimidasole was added to 8.8 g 3- oxocyclopentancarboxylic acid (0.072 moles) in 240 ml methylene chloride at 20°-25°C and stirred for 2 hours at room temperature. Then 16.0 g 1,6- diamino-1,3-di-n-propyluracil (0.072) at 20°-25°C was added and was stirred 3 hours at room temperature. The mixture was evaporated in vacuum to dryness. The residue oil was diluted with 3200 ml water, 35 g of calcium hydroxide was added and all taken was heated at 80°C for 0.5 hour by stirring. The mixture was cooled to 5°C, acidified with pH 1-2 with hydrochloric acid and extracted with CH2Cl2 (3x100 ml). The organic phase was washed with 1x100 ml water and dried over magnesium sulfate. The solution was purified with of 350 g silica gel S 160. CH2Cl2 : CH3OH (99:1) was used as eluent. Refined residue was evaporated and treated with 100 ml ether. 11.5 g 1,3-dipropyl-8-(3-oxocyclopentyl)xanthyne (apaxifylline) obtained (50.2 %). MP: 164-168°C.

Therapeutic Function

Adenosine A1-antagonist, Nootropic

Raw materials

Preparation Products