MOTRETINIDE

Originator

Tasmaderm,Roche,Switz.,1981

Uses

Keratolytic.

Definition

ChEBI: Motretinide is a retinoid.

Manufacturing Process

228 g of 5-(4-methoxy-2,3,6-trimethyl-phenyl)-3-methyl-penta-2,4-diene-1- triphenylphosphonium bromide are introduced under nitrogen gassing into 910 ml of dimethylformamide and treated with cooling at 5°C to 10°C within 20 minutes with 17.5 g of a suspension of sodium hydride (about 50% by weight) in mineral oil. The mixture is stirred for 1 hour at about 10°C, then treated at 5°C to 8°C dropwise with 61.8 g of 3-formylcrotonic acid butyl ester, heated for 2 hours at 65°C, subsequently introduced into 8 liters of icewater and, after the addition of 300 g of sodium chloride, thoroughly extracted with a total of 18 liters of hexane. The extract is washed 5 times with 1 liter of methanol/water (6:4 parts by volume) each time and 2 times with 1.5 liters of water each time, dried over sodium sulfate and evaporated under reduced pressure to leave 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7- dimethyl-nona-2,4,6,8-tetraen-1-oic acid butyl ester, MP 80°C to 81°C as the residue.
125.8 g of 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8- tetraen-1-oic acid butyl ester are introduced into 2,000 ml of absolute ethanol and treated with a solution of 125.8 g of potassium hydroxide in 195 ml of water. The mixture is heated to boiling under nitrogen gassing for 30 minutes, then cooled, introduced into 10 liters of ice-water and, after the addition of about 240 ml of concentrated hydrochloric acid (pH 2-4), thoroughly extracted with a total of 9 liters of methylene chloride. The extract is washed with about 6 liters of water to neutrality, dried over calcium chloride and evaporated under reduced pressure. The residue is taken up in 700 ml of hexane. The precipitated 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8- tetraen-1-oic acid melts at 228°C to 230°C.
28.6 g of 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8- tetraen-1-oic acid are introduced into 300 ml of benzene and treated under nitrogen gassing with 12 g of phosphorus trichloride. The benzene is subsequently distilled off under reduced pressure. The remaining 9-(4- methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid chloride is dissolved in 1,200 ml of diethyl ether. The solution is added dropwise at -33°C into 500 ml of ethylamine and stirred for 3 hours. The reaction mixture is then diluted with 500 ml of diethyl ether and stirred without cooling for a further 12 hours, the ammonia evaporating. The residue is dissolved in 10 liters of methylene chloride. The solution is washed 2 times with 3 liters of water, dried over sodium sulfate and evaporated under reduced pressure. The remaining N-ethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7- dimethylnona-2,4,6,8-tetraen-1-oic acid amide melts, after recrystallization from ethanol, at 179°C to 180°C.

brand name

Tasmaderm (Hoffmann-LaRoche).

Therapeutic Function

Antipsoriatic

Raw materials

Preparation Products