Piperidine 1-amino

It has been found that the tris(tert-butyloxycarbonyl) protected hydantoin of 4-piperidone 2, selectively hydrolyses in alkali to yield the N-tert-butyloxycarbonylated piperidine amino acid 3. The hydrolysis, which is performed in a biphasic mixture of THF and 2.0M KOH at room temperature, cleanly partitions the deprotonated 4-amino-N -(tert-butyloxycarbonyl)piperidine-4-carboxylic acid into the aqueous phase of the reaction with minimal contamination of the hydrolysis product, di-tert-butyl iminodicarboxylate, which partitions into the THF layer. Upon neutralization of the aqueous phase with aqueous hydrochloric acid, the zwitterion of the amino acid is isolated. The Bolin procedure to introduce the 9-fluorenylmethyloxycarbonyl protecting group efficiently produces 4.8 This synthesis is a significant improvement over the previously described method9 where the final protection step was complicated by contamination of the hydrolysis side-product, di-tert-butyl iminodicarboxylate, which is very difficult to separate from 4, even by chromatographic means. 

Thus reduction of the 5-thiocyanato group of 151 by zinc (333, 360, 361) or aqueous sodium sulfide (348. 362), hydrolysis of the thiouronium group (7, 363, 364), and deacetylation of the 5-acetylthiothiazole with cold piperidine (365) have been performed to yield the 5-mercapto-thiazole (Scheme 78). It must be pointed out that depending on the experimental conditions, bis(5-thiazolyl(sulfide may be observed as a byproduct (363, 365). Thus 5-amino-4-methylthiazole (152) treated with... 

The succinimide derivative (234) can be used in peptide synthesis for conversion of amino acids into their succinimide esters (235 Scheme 41) (79CL1265). 3-Substituted mercapto-1,2-benzisothiazole 1,1-dioxides (236) have been recommended as an odourless means of storage of thiols. The latter are readily regenerated by the action of piperidine (81CL1457). 

C chemical shifts, 2, 15 Piperidine, 2-aIkyI-JV-nitro-conformation, 2, 160 Piperidine, 4-amino-synthesis... 

The action of anabasine is similar to that of nicotine. When the piperidine ring of anabasine is opened to produce 8-amino-8-3-pyridyl-n-valeric acid the activity is reduced, and this is also true of the corresponding lactam and the benzoyl derivative. According to De Eds myosmine is less toxic than nicotine but more active on isolated guinea-pig intestine. ... 

The cyclic thioketone, 3-oxotctrahydrothiophene (11), gives a mixture of enamines (12,13) when caused to react with a secondary amine such as piperidine or pyrrolidine (31). The enamine mixture can be reduced to the 3-aminotetrahydrothiophene using formic acid or oxidized to the 3-amino-thiophene using diisopentylsulfide. 

Additional evidence that a dynamic equilibrium exists between an enamine, N-hemiacetal, and aminal has been presented by Marchese (41). It should be noted that no acid catalysts were used in the reactions of aldehydes and amines discussed thus far. The piperidino enamine of 2-ethylhexanal (0.125 mole), morpholine (0.375 mole), and p-toluene-sulfonic acid (1.25 x 10 mole) diluted with benzene to 500 ml were refluxed for 5 hr. At the end of this time the enamine mixture was analyzed by vapor-phase chromatography, which revealed that exchange of the amino residue had occurred in a ratio of eight morpholine to one piperidine. Marchese proposed a scheme [Eqs. (4), (5) and (6)] to account for these... 

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). 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

Eda and Kurth applied a similar solid-phase combinatorial strategy for synthesis of pyridinium, tetrahydropyridine, and piperidine frameworks as potential inhibitors of vesicular acetylcholine transporter. One member of the small library produced was prepared from amino-functionalized trityl resin reacting with a 4-phenyl Zincke salt to give resin-bound product 62 (Scheme 8.4.21). After ion exchange and cleavage from the resin, pyridinium 63 was isolated. Alternatively, borohydride reduction of 62 led to the 1,2,3,6-tetrahydropyridine 64, which could be hydrogenated to the corresponding piperidine 65. 

The same amino compounds also underwent reactions with a series of 3-cyano-4-imino- and 3-cyano-4-oxo-piperidines to yield 4-amino-5,0,7,8-tetrahydropyrido[4,3-d]pyrimidines. . A tetra-hydropyTido[4,3-prepared from 4-amino-l-henzyl-3-cyano-d -piperidine (134) hy a simple one-step preparation. This method is of general application for the preparation of fused pyrimidines and previous papers in this field are listed by Taylor. ... 

In non-polar solvents, the reaction with piperidine is best represented by a two-term kinetic form indicating a mixed 2nd- and 3rd-order reaction. Also, base catalysis by tri-ri-butylamine was observed. This kinetic pattern is strongly reminiscent of the results obtained with nitro-activated benzenes.Another interesting result is that stepwise replacement of chlorine atoms by amino groups results in marked... 

These factors are sufficient to produce similar amounts of aminated isomers from 2,4-dichloropyrimidine which gives predominantly 4-alkoxylation products. Thus, a mixture of 2-amino-4-chloro- (302) and 4-amino-2-chloro-pyrimidine (303) is obtained on treatment of 2,4-dichloropyrimidine with alcoholic ammonia (25°, <18 hr), the reagent here being better at hydrogen bonding than piperidine. 

The 3-amino-8-oxo derivative of 1,2,4,5,7-pentaazanaphthalene (475) is known as well as various 3-substituted derivatives of the 6,8-dioxo compound. The 3-methylthio- and 3-ethylthio-6,8-dioxo derivatives and their 7-methyl and 5,7-dimethyl analogs were prepared by ring-closure. 3-Ethylthiopyrimido[4,5-e]-as-triazine-6,8-dione was 3-substituted with alkali 2N, 100°, > 30 min) or acid 2N, 100°, < 2 hr, 70% yield) and with ammonia, aniline, piperidine, or monoalkylamines (in pyridine, 115°, 4 hr, 75-85% yield). ... 

Aliphatic and aromatic aldehydes condensed with 2-amino-(62BRP898414), 5-amino- (80AJC1147), or 8-amino-l,2,4-triazolo[l,5-cjpyrimidines (68JOC530) to give the related Schiff bases. Treatment of the 2-amino-5-methyl-l,2,4-triazolo[l,5-c]quinazoline 11 with formaldehyde and piperidine in the presence of acetic acid gave the 2-hydroxymethyl-amino-5-(2-piperidinoethyl) derivative 172. Utilization of aromatic aldehydes and piperidine in this reaction gave the 2-arylideneamino-5-styryl derivatives 173 (68CB2106) (Scheme 67). 

Aminobutenones of Z-configuration having at least one hydrogen atom attached to the amino group (80MI1) condense with aldehydes (EtOH, piperidine acetate, 25°C, 12 h) in 2 1 ratio to form 1,4-dihydropyiidine derivatives 290 (50NKZ1061). 

Dicyano-2,4,8-triphenyl-7-phenylsulfonyl-6/f-pyrido[], 2-a]pyrimi-dine-6-thione was obtained in the reaction of 6-amino-1-benzoyl-5-cyano-4-phenyl-3-phenylsulfonylpyridin-2(]//)-one and benzylidenemalononitrile in the presence of piperidine in boiling dioxane for 4h in 59% yields (98M1049). 

Cyclization of l-(A -substituted aminocarbonyl)-3-[(tert-butoxycarbonyl) amino]- and -3- [Ai -(tert-butoxycarbonyl)tryptophyl]amino -2-(ethoxycar-bonylmethyl)piperidines (e.g. 188) on the action of NaH gave 2-substituted 5-(substituted amino)perhydropyrido[l,2-c]pyrimidine-l,3-diones (e.g. 159 and 189) (97JMC3402, 97MIP16, 98MI63, 0UMC2219). Cyclization could be also carried out in the presence of DBU (01JMC2219). 

Substitution of an alicyclic ring for one of the aromatic rings in the amino alcohols such as 32 or 39 produces a series of useful antispasmodic agents that have found some use in the treatment of the symptoms of Parkinson s disease. Mannich reaction of acetophenone with formaldehyde and piperidine affords the amino-ketone, 44a. Reaction of the ketone with cyclohexylmagnesium... 

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