Piperidyl

Many of the substitution reactions of 2,3 -bipyridine have been conducted using anabasine (12 R = H) as starting material, which presumably is dehydrogenated to 2,3 -bipyridine prior to substitution. Chlorination of anabasine (as the hydrochloride) at 220-230°C affords 5-chloro-2,3 -bipyri-dine. Isoanabasine [2-(3-piperidyl)pyridine] behaves similarly on chlorination. 2,3 -Bipyridine is fully chlorinated to octachloro-2,3 -bipyridine by... 

Direct sulfonation of thiazole, as well as of 2-substituted thiazoles, leads mostly to substitution m the 5-position (330-332). 4-Thiazole sulfonic acid has been prepared through direct sulfonation of 2.5-dibromothiazole with subsequent Rane% Ni reduction (330). Sulfonation of 2.5-dimethyl- and 2-piperidyl-5-methylthiazoles affords the corresponding 4-sulfonic acids as barium salts (247). The 2-hydroxy group facilitates the sulfonation (201. 236). When the 4- and 5-positions are occupied direct sulfonation can occur in the 2-position. 5-hydroxyethyl-4-methyl-2-thiazole sulfonic acid has been prepared in this manner (7). 

Piperidyl (from piperidine) Quinolyl (from quinoline) Isoquinolyl... 

Also, piperidino- and morpholino- are preferred to 1-piperidyl- and 4-morpholinyl-, respectively. 

Denotes position of double bond, t For 1-piperidyl, use piperidino. 

Finally, benzpiperylon or l-(l-methyl-4-piperidyl)-3-phenyl-4-benzyl-2- (or 3-) pyrazolin-5-one has been utilized by Sandoz as an investigational agent in connective tissue disorders (B-76MI40404). 

Folic acid, 5-methyltetrahydro-biological activity, 3, 325 oxidation, 3, 308 Folic acid, iV-nitroso-carcinogenicity, 1, 141 Folic acid, 10-oxa-synthesis, 3, 327 Folic acid, 4-piperidyl-hydrolysis, 3, 294 Folic acid, 5,6,7,8-tetrahydro-chirality, 3, 281 synthesis, 1, 161 Folic acid, 10-thio-synthesis, 3, 327... 

Constitution. On oxidation with chromic acid, conhydrine yields Z-piperidyl-2-earboxylic acid. It is converted into Z-coniine either by reduction of the iodo-derivative (iodoconiine), C,HijNI, formed by the action of hydriodic acid and phosphorus at 180° or by hydrogenation of the mixture of coniceines produced, when it is dehydrated by phosphorus pentoxide in toluene. These and other observations indicate that the p- ygen atom must occur as a hydroxyl group, in the w-propyl side-chain in either the a- (XV) or (XVI) position, since the y-position would involve... 

Girgensohnia spp. G. diptera Bge. contains N-methylpiperidine and dipterine, CHH14N2, m.p. 87-8°, [a]D 0° hydrochloride, m.p. 177-8°, picrate, m.p. 189-190°, and picrolonate, m.p. 242-3°, which was later shown to be N-methyltryptamine.i G. oppositiflora Pall, contains N-methylpiperidine and girgensonine, C13H13ON2, m.p. 147-8°, [aJjj 0°. The latter forms a hydrochloride, m.p. 145-8°, and a picrolonate, m.p. 192-4°, and on hydrolysis by alkali yields piperidine, hydrocyanic acid and p-hydroxybenzaldehyde, indicating that it is N-piperidyl-p-hydroxy-phenylacetonitrile, and this has been confirmed by comparison with a synthetic specimen. ( (1) Juraschevski and Stepanova, J. Gen. Chem. Russ., 1939, 9, 2203 Juraschevski, ibid., 1940, 10, 1781. (2) Juraschevski and Stepanova, ibid., 1946, 16, 141). 

Schopf et al. 188,189) observed that -tetrahydroanabasine salts contain a molecule of water or methanol. According to infrared spectra, they exist as 2-hydroxy- or 2-methoxy-3-(2-piperidyl)piperidine salts (97). Salt 99, obtained by a transannular cyclization reaction taking place on neutralization of bicyclic amino ketone 98, also belongs to this group 181). 

V. -(l-Carbobemoxy-4 -piperidyl)propionyl chloride. /3-(iV-carbo-benzyloxy-4-piporidyl)ethyl 3-indolyl ketone (208) was obtained similarly by the condensation of ]3-(A -carbobenzoxy-4-piperidyl)-propionyl chloride with indole magnesium bromide in ether. ... 

A search has not been made for products of displacement of halogen from the benzo-ring in polyhalo compounds, but it is clear that the major mono-substitution occurs in the azine ring. For example, 2,6- and 2,7-dichloroquinoxalines give 70-80% of the 2-amination product with )S-diethylaminoethylamine (150°, 2 hr) or y-(l-piperidyl)-propylamine (220°, 2 hr). 2,3,6-Trichloroquinoxaline gives with... 

Treatment of 9-(ethoxymethoxy)-3- 2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-1,2,5,6-tetrahydro-1 -pyridyl] and -1 -piperidyl]ethyl -2-methyl-4/f-pyrido-[1,2-rz]pyrimidin-4-ones with cone. HCl afforded 9-hydroxy derivatives (95MIP4, OOMIPIO). 

Methyl 2-substituted perhydropyrido[l,2-u]pyrazine-8-acetates were obtained by catalytic hydrogenation of 2-substituted 8-(methoxycarbonyl-methylene)perhydropyrido[l,2-a]pyrazines over 10% Pd/C catalysts (00JAP(K)00/86659). A side chain 4-pyridyl group was hydrogenated over Pt02 catalysts to yield a 4-piperidyl derivative. 

Amine bound to a Wang-polystyrene resin 381 was acylated with 4-oxo-4Ff-pyrido[l,2-u]pyrazine-3-carboxylic acid in the presence of bromotrispyrrolidinophosphonium hexafluorophosphate and /-Pr2NEt in A-methylpyrrolidone (98MIP16). l-(4-Cyclohexyl-4-r / r-butylaminocarbo-nyl-l-piperidyl)-2-(4-fluorophenyl)ethylamine was acylated with perhydro-pyrido[l,2-u]pyrazine-3-carboxylic acid (01MIP19). An amino group of a macrocyclic compound attached to a solid support was acylated with... 

The placement of a nitrogen atom directly on the benzilic carbon atom is apparently consistent with antispasmodic activity. Esterification of 2 (iV-piperidyl)ethanol by means of chloroacyl chloride (68) gives the basic ester (69). Displacement of the remaining halogen by piperidine gives dipiproverin (70). ... 

Preparation of 4-aza-S-(N-methyl-4-piperidyll-10,11-dihydro-SH-dibenzo[a,d]cycloheptene-S-ol Add 17.4 g of N-methyl-4-chloropiperidine to a stirred mixture containing 3.2 g of magnesium, 20 ml of anhydrous tetrahydrofuran, 1 ml of ethyl bromide and a crystal of iodine. Reflux for two hours, cool to 30°-35°C and add a solution of 13 g of 4-aza-10,11 -dihydro-5H-dibenzo[a,d] cycloheptene-5-one in 25 ml of tetrahydrofuran. Stir for five hours, remove the solvent by distillation in vacuo and add 250 ml of ether. Add 100 ml of 10% ammonium chloride solution and extract the mixture with chloroform. Concentrate the chloroform solution to a residue and recrystallize from isopropyl ether obtaining 20 g of the carbinol,... 

A mixture of 3.4 parts of 7-chloro-4-fluorobutyrophenone, 4 parts of 1-(4-piperidyl)-2-benzimidazolinone hydrochloride, 6 parts of sodium carbonate and 0.1 part of potassium iodide in 176 parts of 4-methyl-2-pentanone is stirred and refluxed for 48 hours. The reaction mixture is cooled and 120 parts of water is added. The separated organic layer is dried over magnesium sulfate and the solvent is evaporated to leave an oily residue which is dissolved in dilute hydrochloric acid and boiled. The acidic solution is filtered and cooled at room temperature whereupon there crystallizes from solution l-<1-[ y-(4-fluorobenzoyl)-propyl]-4-piperidvl>-2-benzimidazolinone hydrochloride hydrate melting at about 134°-142°C. 

Cyclopentyl- 3-(N-piperidyl)ethyl ketone Manufacturing Process... 

The manufacture of the cyclohexyl analog is as follows. Phenyl magnesium bromide was prepared from 48.5 g (0.308 mol) of bromobenzene, 7 g (0,29 mol) of magnesium, and 125 ml of dry ether. To it was added at 5°C over a period of A hour 40 g (0.18 mol) of cyclohexyl (3-(N-piperidyl)-ethyl ketone (BP 115° to 117°C/1 mm) in 125 ml of dry ether. The mixture was allowed slowly to come to room temperature, refluxed for one hour, and then poured into ice containing 80 ml of concentrated hydrochloric acid. Ammonium chloride (100 g) and 200 ml of concentrated ammonium hydroxide were added and the organic layer was separated. After drying and removing the solvent, the residue was distilled under reduced pressure. The base distilled at 158° to 170°C (1 mm) and solidified. Upon recrystallization from methanol it melted at 112° to 113°C. 

Chemical Name (+)-1 -Benzyl-4-[(2,6-dioxo-3-phenyl)-3-piperidyl] piperidine Common Name Dexbenzetimide dextrobenzetimide benzetimide Structural Formula ... 

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