Methyl-8-azabicyclo octan

There are eight possible stereoisomeric forms of methyl 3-(benzoyloxy)-8-methyl-azabicyclo[3.2.1 ]octan-2-carboxylate, of which one, R-cocaine, is simply referred to as cocaine. Chemically, cocaine is known as 2R-carbomethoxy-3S-benzyloxy-1 R-tropane. Cocaine is naturally occurring in a variety of plants belonging to the Erythroxylon coca species, which is indigenous to some countries in South America. In addition to its stimulant actions, cocaine possesses vasoconstrictor actions and is a local anesthetic it has served as a template for the development of other therapeutically useful agents, including local anesthetics and S-HTs serotonin antagonists. 

Chemical Name 3-(Diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1 ] octane methanesul-fonate... 

Benziloyloxy-1-azabicyclo[2.2.2] octane methobromide was prepared by adding 20 cc of a 30% solution of methyl bromide in ether to a solution of 2.5 g of 3-benziloyloxy-1-azabicyclo[2.2.2] octane in 20 cc of chloroform. After standing for 3 hours at room temperature and 15 hours at -i-5°C, a crystalline precipitate had formed. This was filtered off and recrystallized from a mixture of methanol, acetone, and ether prisms melting at 240° to 241°C. 

The tropane alkaloids contain as a common structural element the azabicyclo [3.2.1] octane system, and the systematic name of tropane is 8-methyl-8-azabicyclo [3.2.1] octane (Fig. 1). Contradictory results concerning the C-6 and/or C-7 substitution of several C-3,C-6- and C-3,C-7-disubstituted and C-3,C-6,C-7-trisubstituted tropane alkaloids have been presented in the literature. In many cases both optical antipodes of these tropane alkaloids are known, either separately or as a racemic mixture. 

Huscroft et al. [15] reported a new series of conformationally constrained hNKl antagonists containing an 8-azabicyclo[3.2.1]octane core. The N-2 methyl tetrazole analogue 11 had an attractive profile with high hNKl affinity (1 nM) and long lasting... 

A comparison of structures of V-methyl-V-nitroso-p-nitrobenzamide, N,N -dimethyl-V-nitrosourea, V-methyl-V-nitrosourea, 2-nitroso-2-azabicyclo[2.2.2]octan-3-one to those of V-methyl-V -nitro-V-nitrosoguanidine and V,V -dimethyl-V"-cyano-V-nitrosoguanidine shows that the N—N and C—NNO bond lengths in the nitroguanidines44 are similar to those found in the nitrosoamides, but that the corresponding bonds in... 

The populations of the rotamers are affected by steric effects. Karabatsos and Taller (77) examined the populations of unsymmetrical nitrosamines and found that in methyl-terr-butylnitrosamine only one isomer was observable. Nelsen and associates (78) similarly found that the populations of conformers of 2-nitroso-2-azabicyclo[2.2.2]octanes (40) are affected by the substituent in the 3-position. 

The initial medicinal chemistry route to the azabicyclo[3.3.0]octane-3-carboxylic acid produced the azabicyclo system in a diastereoselective but racemic manner, and required a classical resolution to achieve enantioenriched material (Teetz et al., 1984a, b 1988). Reaction of (R)-methyl 2-acetamido-3-chloropropanoate (43) and 1-cyclopentenylpyrrolidine (44) in DMF followed by an aqueous acidic work-up provided racemic keto ester 45 in 84% yield (Scheme 10.11). Cyclization of 45 in refluxing aqueous hydrochloric acid provided the bicyclic imine, which was immediately reduced under acidic hydrogenation conditions. The desired cis-endo product 46 was obtained upon recrystaUization. The acid was protected as the benzyl ester using thionyl chloride and benzyl alcohol, providing subunit 47 as the racemate. Resolution of 47 was accomplished by crystallization with benzyloxy-carbonyl-L-phenylalanine or L-dibenzoyl-tartaric acid. 

Hoechst has reported an enantioselective approach toward the key azabicyclo[3.3.0] octane-3-carboxylic acid 46 that preserves the stereochemistry of the L-serine-derived starting material (Urbach and Henning, 1991). L-Serine methyl ester (48) was alkylated... 

Analogously, shieldings of antiperiplanar carbons by nitrogen lone pairs have been reported. It was concluded that a considerable part of the 10 ppm difference of the C-2 chemical shifts in the isomers of 8-methyl-8-azabicyclo[3.2.1]octane must be due to lone-pair interaction, since a difference of only 6 ppm is expected from a y-ganche effect of the A-methyl group73. This is supported by the fact that the difference is reduced if the solvent is methanol in this case the lone pairs are involved in hydrogen bridging. 

It has been postulated (60JA2609) that the formation of a quaternary salt of 1-azabicyclo[4.2.0]octane is the first step in the mechanism of its methyl iodide-catalyzed polymerization. 

CHEMICAL NAME = 8-Azabicyclo[3.2.1] octane-22carboxylic acid, 3-(benzoyloxy)-8-methyl-, methyl ester CAS NUMBER = 50-36-2 MOLECULAR FORMULA = C17H21N04 MOLAR MASS = 303.4 g/mol COMPOSITION = C(67.3°/o) H(7.0%)... 

A 7-substituted 3,4,6,7-tetrahydro-2//-pyrido[2,l-h][l,3]oxazine was formed as by-product the alkylation of methyl 2-(benzyloxycarbonyl-6-oxo-l-phenylsulfonyl)indol-2-yl)-2-azabicyclo[2,2,2]octane-6-enrfo-car-boxylate with 3-iodopropanol from a 3-substituted l-(3-hydroxypropyl)-2,3-dihydropyridinium intermediate (90JOC6028). 

From the reaction mixture of 3-methyl-2-/er/-butyl-6,7,8,9-tetrahy-dropyrido[l,2-a]pyrimidin-4-one 653 in a 1 2 mixture of acetic acid and acetonitrile under argon at 0°C, after photolysis with a high-pressure mercury lamp, 6-acetoxy-l-azabicyclo[4.2.0]octan-8-one 654, 1-azabicyclo [4.2.0]oct-5-en-8-one 655, and piperidone derivative 656 could be isolated in 72%, 7%, and 1% yields, respectively [88JCS(P1)2653]. 

An ab initio study of the acid hydrolysis of the lactam l-azabicyclo[2.2.2]octan-2-one (described as a highly twisted amide ) and of the model compound 3-methyl-S-valerolactam showed that both proceed via a stepwise mechanism, but A-protonation is preferred to O-protonation by the twisted amide , whereas the reverse is the case for the model compound.92... 

AZABICYCLO(3.2.1)OCTANE-2-CARBOXYLIC ACID, 3-(BENZOYLOXY)-8-METHYL-, PROPYL ESTER,HYDROCHLORIDE (lR-(2-endo.3-exo))-... 

A solution of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-l,4-benzoxazine-8-carboxylic acid in tetrahydrofuran and dimethylformamide is cooled to below 0°C and triethylamine is added under stirring thereto. Further, ethyl chlorocarbonate is added and the mixture is stirred at room temperature. To the resultant mixture is added 3-amino-8-azabicyclo[3.2.1]octane and the mixture stirred. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off to give 6-chloro-3,4-dihydro-4-methyl-N-(8-azabicyclo[3.2.1]oct-3-yl)-3-oxo-2H-l,4-benzoxazine-8-carboxamide. 

Chemical Name Spiro(l-azabicyclo(2.2.2)octane-3,5 -(l,3)oxathiolane), 2 -methyl-, hydrochloride, hemihydrate, cis-... 

Dihydro-10,10-dioxo-l l-methyldibenzo[c,f][l,2]thiazepin-5-yloxy)tropane and the hydrogen maleate salt thereof. (This name was given by the authors of U. S. Patent No 3 700 633. It corresponds to endo-6,11-dihydro-6-methyl-ll-[(8-methyl-6-azabicyclo[3.2.1]oct-3-yl)oxy]dibenzo[c,f] [l,2]thiazepine 5,5-dioxide and 6,ll-dihydro-6-methyl-ll-(8-methyl-8-azabicyclo[3.2.1]octan-3a-yloxy)dibenzo[cf][l,2]thiazepin-5,5-dioxide). 

TA belong to a class of small molecules characterized by a derivatized tropane ring skeleton (8-methyl-8-azabicyclo[3.2.1]octane). Hydroxylated tropane (tropine) is esterified with diverse organic acids often representing structural analogues of, e.g. tropic, benzoic or mandelic acid (Fig. 1). Manifold variations are found either in natural sources or as (semi-) synthetic active pharmaceutical ingredients (API) with individual optimized properties. 

Anisodamine (Ada C17H23N04 MW 305.16 g/mol CAS-No 55869-99-3 [(lS,3S,5S,7S)-7-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-3-yl](2S)-3-hydroxy-2-phenyl-propanoate). 

Gordon WP, Cheng H, Larsen DL, Ragner JA, Landmesser NG (1992) identification of urinary metabolites of 8-methyl-8-azabicyclo-[3,2,l] octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey. Drug Metab Dispos 20 596-602... 

Oxa-3-azabicyclo[3.2.1]octan-2-one (65) derived from methyl furoate was allowed to polymerize in bulk with its N-acetyl derivative as the initiator, and... 

Ifenprodil (= l-Methyl-2-hydroxy-2-(4-hydroxyphenyl) ethyl-1 -(4-benzyl-piperidine)] -(aryl piperidine) [at(/o-3-(Indol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane] (indolotropane) [Kynurenic acid (= 4-Hydroxy-2-quinolinecarboxylic acid)] (quinoline carboxylic acid) [Memantine (= 1-Amino-3,5 dimethyladamantane)] (amino adamantane, amino cyclic aliphatic) [Methadone (= 6-Dimethylamino-4,4-diphenyl-3-heptanone)] (aryl tertiary amine) [em/o-3-(l -Methylindol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane(indolotropane) exo- 3-( 1 -Methylindol-2-yl)-8-methyl-8-... 

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