Pipamperone

Chemical Name 1 -[4-(4-Fluorophenyl)-4-oxobutyl] -[1.4 -bipiperidine] -4 -carboxamide Common Name Floropipamide Structural Formula  

Piperidine hydrochloride 1 -Benzyl-4-piper idone 7-Chloro-4-fluorobutyrophenone 

To a stirred soiution of 130.4 parts of potassium cyanide and 243.2 parts of piperidine hydrochloride in a mixture of 800 parts of water and 320 parts of ethanol is added portionwise 378 parts of 1 -benzyl-4-piperidone. After about one hour a soiid starts to precipitate. Stirring is continued for 24 hours. The reaction mixture is filtered and the solid is recrystallized from 1,200 partsof diisopropyl ether. On cooling to room temperature a first cropof 1-benzyl-4 yano-4-piperidinopiperidine melting at about 104°C to 106°C is obtained. By concentrating and further cooling of the mother liquor a second crop of the above compound is obtained. 

A mixture of 14.1 partsof 1-benzyi-4-cyano-4-piperidinopiperidine and 40 parts of 90% sulfuric acid is heated on a steam bath for 10 minutes. Without further heating, the mixture is stirred until a temperature of about 20°C is obtained. The mixture is then poured into 150 parts of ice ater and the resultant solution is aikaiized with excess ammonium hydroxide solution. The aqueous solution is decanted from the precipitated oil. On treating this oil with 80 parts of acetone, crystallization sets in. After one hour the solid is filtered off and dried to yield 1 -benzyl-4-piperidinopiperidine-4-carboxamide melting at about 137.5°C to 140°C. 

A mixture of 215 parts of 1 -benzyl-4-piperidinopiperidine-4-carboxamide, 1,200 parts of iso-propyi alcohol, 1,000 parts of distilled water and 157 parts of hydrogen chloride is debenzyl-ated under atmospheric pressure and at a temperature of about 40 C in the presence of 40 parts of a 10% palladium-on-charcoal catalyst. After the calculated amount of hydrogen is taken up, hydrogenation Is stopped. The mixture is filtered and the filtrate is evaporated. 

To a mixture of 4.1 parts of 4-piperidinopiperidine-4-carboxamide, 6.4 parts of sodium carbonate, and a few crystals of potassium iodide in 100 parts of anhydrous toluene is added drop-wise a solution of 5.6 parts of 7-chloro-4-fluorobutyrophenone and 40 parts of anhydrous toluene at a temperature of 30% to 40%. The mixture is stirred and refluxed for 48 hours. The reaction mixture is cooled and divided between 50 parts of water and 60 parts of chloroform. The combined organic layers-tolueneand chloroform-are dried over potassium carbonate, filtered, and evaporated. The oily residue solidifies on treatment with 80 parts of ether. After cooling for 30 minutes at 0%, there is obtained 1 -(7-(4-fluorobenzoyl)propyl] -4-pi-peridinopiperidine-4-carboxamide melting at about 124.5% to 126%. 

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Phenyl toloxamine o-Benzylphenoxy-/3-chloropropane Benproperine 4-Benzylplperldine Ifenprodil tartrate 1 -Benzyl-4-piperidone Fentanyl Pipamperone Tinoridine... 

Ch oro -p-fluorobutyrophenone Benperidol D roper idol Melitracen Pipamperone Spiperone... 

C12H15NO 3612-20-2) see Alfentanil Clebopride Fentanyl Fluspirilene Pipamperone "nnoridine Trifluperidol... 

C j,H27N30 7762-50-7) see Pipamperone 7V-benzyl-3-piperidinyl acetoacetate (C 7,H2iN03 85387-34-4) see Benidipine l-benzyl-4-piperidone see under l-benzylpiperidine-4-one... 

C H oClFO 3874-54-2) see Benperidol Bromperidol Droperidol Fluanisone Haloperidol Melperone Moperone Pipamperone Primaperone Spiperone Timiperone Trifluperidol... 

Yet another (see lenperone) butyrophenone related to haloperidol is pipamperone (64). N-benzyl-4-piperidone (60) has a venerable history as starting material for both central analgesics and CNS drugs. This synthon has been used by the Janssen group as a building block for numerous such drugs. Reaction of... 

Phenylbutazone, 388, 474 Phenylephrine, 265 Phenylpiperidinols, 334 Physical dependence, 314 Pill, the, 137, 164 for canines, 144 Pimetine, 286 Pimozide, 290 Pindolol, 342 Pinoxepin, 419 Pipamperone, 288 Pipobroman, 299 Piposulfan, 299 Piprozolin, 270 Piquizil, 381 Pi randamine, 459... 

C. Shiue, J.S. Fowler, A.P. Wolf, M. Watanabe, C.D. Arnett, Synthesis and specific activity determination of NCA F-labeled butyrophenone neuroleptics Benperidol, haloperidol, spiroperidol and pipamperone, J. Nucl. Med. 26 (1985) 181-186. 

Butyrophenones are a very old family of nonspecific antagonists of dopamine. Nevertheless, haloperidol and its close analogues melperone, bromperidol, trifluperidol) are still marketed. Timiperone, biriperone, benperidol, droperidol, fluanisone, and pipamperone have more structural changes in the piperidine moiety (Figure 8.28). 

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