1 -Methyl-4- piperazine

The initial strategy to improve potency and selectivity focused on substitution on and around the piperazine (218). Chirality of the piperazine 2-methyl was used to improve potency and selectivity, as demonstrated by the preference for the (2s)-methylpiperazine (51) (CCR5 K, = 28 nM, Mg = 485 nM). The absence of any substitution at the 2-position... 

Amino-2-chloro-6,7-dimethoxyquinazoline N-(l,4-benzodioxan-2-carbonyl)piperazine Methyl sulfate... 

It was shown (88DDRP254219) that perfluorinated compounds can be obtained by ECF of 1,4-dimethyl-1,4-homo-piperazine, methyl-4-ethylhomopiperazin-l-yl acetate, and l,4-i is-(methoxycarbonylmethyl)-1,4-homopiperazine. However, the yields of perfluorinated products are very low. 

Aliphatic Alcohols and Alkylene Glycols. Simple aliphatic alcohols, such as methanol [67-56-1], can be used to alkylate alkyleneamines. For example, piperazine reacts with methanol over a reductive amination catalyst to yield a mixture of 1-methyl- [109-01 -3J and 1,4-dimethylpiperazine [106-58-1] (12). 

Piperazine, I -diethyIcarbamyI-4-methyl-metabolism, 1, 227 Piperazine, N,JV-dimethyI-epoxy resin curative. 1, 406 Piperazine, 2,5-dioxo-occurrence, 3, 187 Piperazine-2,5-dione polymers, 1, 298... 

Amines or amides Alkyl amines (iindecyloctyl and diamyl methyl amine) polyamides (acyl derivatives of piperazine) Boiler foam sewage foam fermentation dye baths... 

Treatment of the pyrrolidine derivative 130 with sodium hydride followed by A-methyl piperazine afforded pyrrolidino[l,2-a]quinolinone 4-carboxy-late 131 (93JPR397) (Scheme 25). 

Replacement of the methyl group of the piperazine-substituted phenothiazines by some more polar group such as hydroxyethyl fragment leads to a further small increase in potency. It should be noted at this point that all phenothiazines manifest a series of side effects. The given set of these varies, however, with the side chains. The availability of the great variety of such structural variations makes it more likely that some drug will be found that a given individual will tolerate. 

Alkylation of phenothiazine with l-chloro-2-methyl-3-bromopropane affords the methylated analog (80) of the intermediate above. Use of this halide to alkylate the piperazine... 

One-tenth mol (20 g) of benzhydryl chloride was mixed with 0.19 mol (19 g) of N-methyl-piperazine and about 10 cc of benzene and the whole was heated on the steam bath four hours. The contents of the flask was partitioned between ether and water, and the ethereal layer was washed with water until the washings were neutral. The base was then extracted from the ethereal layer by N hydrochloric acid and the extract, made acid to Congo red paper, was evaporated under vacuum, 29.5 g of the pure dihydrochloride of N-methyl-N -benzhydryl piperazine was recovered from the residue by recrystallization from 95% alcohol melting above 250°C with decomposition. 

By operating in this manner 10-(2-methyl-3-chloro-propyl)phenothiazine is obtained. A mixture of 10-(2-methyl-3-chloro-propyl)phenothiazine and 1-[2-(2-hydroxyethoxy)ethyl] piperazine is then heated at 110 -120°C for 20 hours. After cooling, the reaction product is dissolved in 200 cc of benzene and the solution washed several times with water. 

Chemical Name 1 -[Bis(4-fluorophenyl)methyl] -4(3-phenyl-2-propenyl)piperazine Common Name —... 

A solution of 54.1 grams of 1-formyl-4-(3 -chloropropyl)-piperazine, [prepared by formylat-ing 1-(3 -hydroxypropyl)-piperazine by refluxing in an excess of methyl formate, purifying the 1-formyl-4-(3 -hydroxypropyl)-piperazine by vacuum distillation, reacting this compound with an excess of thionyl chloride at reflux and isolating the desired 1-formyl-4-(3 -chloropropyl)-piperazine by neutralization with sodium carbonate solution followed by distillation] in 200 ml of toluene is added. The reflux period Is continued for 4 hours. 

B) A mixture of 2.4 parts of 1 acetyl-4-(4-hydroxyphenyl)piperazine, 0.4 part of sodium hydride dispersion 78% 75 parts of dimethylsulfoxide and 22.5 parts of benzene is stirred for one hour at 40°C. Then there are added 4.2 parts of cis-2-(2,4-dichlorophenyl)-2-(1 H-imidazol-1 -ylmethyl)-1,3-dioxolan-4-ylmethyl methane sulfonate and stirring is continued overnight at 100°C. The reaction mixture Is cooled and diluted with water. The product is extracted with 1,1 -oxybisethane. The extract is dried, filtered and evaporated. The residue Is crystallized from 4-methyl-2-pentanone. The product is filtered off and dried, yielding 3.2 parts (59%) of cis-1-acetyl-4-[2-(2,4-dichlorophenyl)-2-(1 H-imidazol-1-ylmethyl)-13-di-oxolan-4-ylmethoxy] phenyl] piperazine MP 146°C. 

A mixture of 65 parts 1 -[4,4-di-(4-fluoro-phenvl)butyl] -piperazine, 4.33 parts N-(2-chloro-acetyl)-2,6-dimethyl-aniline, 3.2 parts sodium carbonate, a few crystals of potassium iodide in 200 parts 4-methyl-2-pentanone is stirred and refluxed for 70 hours. After cooling there are added 70 parts water. The organic layer is separated, dried over potassium carbonate, filtered and evaporated. The oily residue is dissolved in 80 parts diisopropyl-ether and the solution is filtered hot. After cooling the filtrate at 0°C, the formed solid is filtered off and recystallized from 80 parts ether, yielding 1-[4,4-di-(4-fluoro-phenyl)butyl] -4-[(2,6-dimethyl-anilino-carbonvl)-mathyl] -piperazine MP 159°Cto 161°C. 

Chemical Name 8-Nitro-1,2-dihydro-2-(N-methyl-piperazin-1 -yl)methylene-6-(o-chloro-phenyl)-1 H,4H-imidazo-[ 1,2-a] [ 1,4] -benzodiazepin-1 -one methanesulfonate... 

Chemical Name 1-[(4-Chlorophenvl)phenylmethyl] 4-[(3-methylphenyl)methyl] piperazine hydrochloride... 

Chamical Nama N -2-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetoxyJ-ethyl-N-3-(N-benzoyl-N, N -di-n-propyl-DL-isoglutaminoyl)-oxypropyl piperazine dimaleate... 

Ethy I mercapto-phenothiazine 1 -Methyl-4-(3 -chloropropyl-1 )-piperazine Sodium amide... 

Chemical Name 4-(2-methoxy-2-phenylethy I)-a-(methoxypheny I methyl )-1-piperazine-ethanol... 

Auch mit N-Methyl-piperazin modifizicrtcs Natrium-bis-[2-methoxy-athoxy]-dihydrido-aluminat reduziert Carbonsiiurccstcr mit hohen Ausbeuten zu Aldehyden1. 

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