4-Piperidinecarboxamide

Reductive cyclization of 4-piperidinecarboxamide 562 afforded 563 which could be alternatively obtained by condensation of 564 with the respective cyclic amine. Compound 563 showed inhibition of writhing in mice (96EP700913). Similarly, 565 gave 566 (76JMC1111) (Scheme 94). 

To a stirred and refluxing suspension of 4.95 parts of 4-piperidinecarboxamide, 1 part of sodium iodide and 8.4 parts of potassium carbonate in 40 parts of butanone there are added in the course of 30 minutes9.3 parts of 2-chloro-10-( y"Chloropropyl)phenothiazine in 40 parts of butanone. Stirring and refluxing are continued for 12 hours after which the mixture is cooled and filtered. The filtrate is concentrated under vacuum to give a residue which is recrystallized from a mixture of 2-propanol and petroleum ether. The 1-[ y-(2 -chloro-10 -phenothiazinelpropyl] piperidine-4-carboxamide thus obtained melts at approximately 139°C. 

A mixture of 84 parts of 3,3-diphenyl-3-cyanopropyl bromide, 41 parts of 4-piperidino4-pi-peridinecarboxamide, 64 parts of sodium carbonate, a small amount of potassium iodide and 1,200 parts of anhydrous toluene was stirred, and heated under reflux for 48 hours. At the end of this time the reaction mixture was allowed to cool to room temperature, and 500 parts of water were added. The resultant precipitate was removed by filtration, and triturated with diisopropyl ether. The crystalline material thus obtained was removed by filtration, and re-crystalli2ed from 320 parts of acetone, to give 1 -(3,3-diphenyl-3-cyanopropyl)4-piperidino-4-piperidinecarboxamide, melting at about 149°C to 150°C. 

Chemical Name 4-Piperidinecarboxamide, l-(3-(2-(methylsulfonyl)-10H-phenothiazin-10-yl)propyl)-... 

To a stirred and refluxing suspension of 4.95 parts of 4-piperidinecarboxamide, 1 part of sodium iodide and 8.4 parts of potassium carbonate in 40 parts of butanone there are added in the course of 30 minutes 9.3 parts of 2-chloro-10-(y-chloropropyl)phenothiazine in 40 parts of... 

Chemical Name l-(3,3-Diphenyl-3-cyanopropyl)-4-piperidino-4-piperidinecarboxamide... 

In subsequent investigations by others, Step 7 piperidine- and tetrahydro-2H-thiopyran-sulfonyl derivatives were prepared. These include l-cyclopropyl-N-hydroxy-4-[[4-[4-( 1 -ethylethoxy)-phenoxy] -phenyl]-sulfonyl] -4-piperidinecarboxamide hydrogen chloride, (III), (3) and tetrahydro-4-[[4-trifluoromethyloxy)-phenyl]sulfonyl]-2H-thiopyran-4-carboxamide, (IV), (4). 

Extensive Step 2 derivatives of the current invention including N-hydroxy-2,3-dimethoxy-6-[[4-[4-(trifluoromethyl)phenoxy]-l-piperidinyl)sulfonyl]benzamide (3) and l-(2-furanylcarbonyl)-N-hydroxy-4-[[4- [4-(trifluoromethyl)phenoxy] -1 -piper idiny 1] sulfony 1]-4-piperidinecarboxamide, (III), (4) are provided for review. 

Chemical Name 1-(3,3-DiphenYl-3-cYanopropYl)4-piperidino-4-piperidinecarboxamide Common Name Pirinitramide Structural Formula ... 

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