2- Methyl-5,6,7,8-tetrahydroquinoline

Diethyl (5-acetamido-6-fluor-2-methyl-1,2,3,4-tetrahydroquinolin-l-yl)-methylenemalonate (130, R = F, R1 = NHAc) was cyclized by heating... 

Flumequine was prepared in 84% yield by the cyclization of isopropylidene (6-fluoro-2-methyl-1,2,3,4-tetrahydroquinolin-1 -yl)methylenemalo-nate in polyphosphoric acid at 120-130°C for 30 min [82JAP(K)2285],... 

Sridharan V, Avendano C, Menendez JC (2007) CAN-catalyzed three-component reaction between anilines and alkyl vinyl ethers stereoselective synthesis of 2-methyl-1,2,3,4-tetrahydroquinolines and studies on their aromatization. Tetrahedron 63 673-681... 

C17H15CI3N2O, 7-Chloro-(2,4-dichloropheny1)-4,5-dihydro-1,4-dimeth-yl-3H-1,4-benzodiazepin-2-one, 32B, 164 C17H1gBrNO, 1 -(p-Bromobenzoyl)-2-methyl-1,2,3,4-tetrahydroquinoline, 43B, 341... 

Krasnov V, Levit G, Andreeva I, Grishakov A, Charushin V, Chupakhin O (2002) Kinetic resolution of ( )-2-methyl-1,2,3,4-tetrahydroquinoline and ( )-2-methyhndoline. Mendeleev Commun 12 27-29... 

Betamethasone dipropionate 6-FIuoro-2-methyl tetrahydroquinoline Flumequine... 

Scheme 4 Addition of 2-lithio-2-cyanopropane to N-methyl-(tetrahydroquinoline)Cr(CO)3...

The Bischler-Napieralski synthesis of l-methyl-3,4-dihydroisoquinoline (18) from N-(2-phenylethyl)acetamide (19) in the presence of heat and acid (72) was not predicted by the Electrophilic Aromatic module of CAMEO this module of CAMEO predicted instead the formation of methyl 2-acetyl-phenethylamine, 20 (Scheme 5). In a related case, CAMEO predicted (when the Electrophilic Aromatic module was chosen) that 4-anilino-butan-2-one (21) would undergo intramolecular cyclization to form 4-hydroxy-4-methyl-tetrahydroquinoline, 23 (Scheme 6). Apparently, CAMEO correcdy perceives the eneamine character of 21 as necessary for this reaction to occur. It was noted in this case that ring formation, as predicted by CAMEO, depended upon the presence of mineral acid, but did not occur if a Lewis acid (e.g., stannic chloride) was selected instead as the reagent. It is known, however, that intramolecular cyclization of 21 does occur in the presence of a Lewis acid and yields 4-methyl-quinoline, 22, as product (74). 

In a similar addition to l-methyl-2-alkyl-J -piperideines, l-methyl-8-alkyl-1,2,3,4-tetrahydroquinolines (134) were obtained (Scheme 10) (163). 

Reactions of 3- and 4-piperidone-derived enamines with a dienester gave intermediates which could be dehydrogenated to tetrahydroquinolines and tetrahydroisoquinolines (678). The methyl vinyl ketone annelation of pyrrolines was extended to an erythrinan synthesis (679). Perhydrophenan-threnones were obtained from 1-acetylcyclohexene and pyrrolidinocyclo-hexene (680) or alternatively from Birch reduction and cyclization of a 2-pyridyl ethyl ketone intermediate, which was formed by alkylation of an enamine with a 2-vinylpyridine (681). 

The 6-methylacetylamino-l,2,3,4-tetrahydroquinoline, after nitration and separation of isomers, following reduction and deprotection, gave the 7-amino-6-methylamino derivative, which cyclized with cyanogen bromide. Alkylation of the cyclization products afforded inhibitors of thymidylate synthase, 5-substituted 2-amino-l//-l-methyl-5,6,7,8-tetrahydroimidazo[4,5-g]quinolines 136, designed for use in iterative protein crystal analysis (Scheme 42) (92JMC847). 

A synthesis for the enantiomerically pure 535 was developed starting with D-phenylalanine which upon reaction with methyl chloroformate gave 528 whose reaction with methoxylamine afforded 529. Cyclization with bis(trifluoroacetoxy)iodobenzene in presence of trifluoroacetic acid gave the tetrahydroquinoline derivative 530 which was demethoxylated to give 531. Treatment of 531 with either benzyl chloroformate or... 

Yu and co-workers also used CAN to catalyze an aza-Diels-Alder reaction <06TL3545>. Aryl imines were reacted with /V-vinyl pyrrol idin-2-one or IV-methyl-lV-vinyl-acetamide in the presence of 10 mol% CAN resulting in the desired 2,4-cw-tetrahydroquinolines in good yields. 

In order to clarify the reaction mechanism, 6-deuterio-labeled 3,5-dinitro-l-methyl-2-pyridone (87, 1 mmol) was prepared and heated with cyclohexanone (2 mmol) and ammonia (10 mmol). A mixture of 2-deuterio- (88) and 4-deuterio-3-nitro-5,6,7,8-tetrahydroquinoline (89) was obtained in the ratio 58 42 (Scheme III.49). 

Reduction of quinolines in acid solution at a lead cathode or by dissolving zinc leads to attack on the heterocyclic ring with the formation of 4,4-coupled products, together with the tetrahydroquinoline [82,83]. In the case of 2- and 4-methyl substituted quinolines, dimeric products are obtained in 10 90 % yields. In these processes, dimerization of the one-electron addition product is in competition with further reduction to give the 1,4-dihydroquinoline, The latter is an enamine and it... 

The reductive route used to prepare heterocyclic enamines has the advantage of avoiding the hydroxylation reaction sometimes found in the mercuric acetate oxidation of saturated heterocyclic amines [126]. The lithium-n-propyl-amine reducing system has been used by Leonard to reduce julodine to A5-tetrahydrojulolidine (66% yield) and l-methyl-l,2,3,4-tetrahydroquinoline to a mixture of enamines (87% yield), consisting of l-methyl-A8-octahydro-quinoline and 1-methyl-A9-octahydroquinoline [135] (Eqs. 51, 52). 

Methylpseudourea, 167,179 l-Methyl-l,2,3,4-tetrahydroquinoline, 111 N-Methyl-N-(3,5,5-trimethylhexyl)-p-nitro-... 

To a dry flask containing 415 ml of n-propylamine and 10.15 gm (1.45 gm-atoms) of chopped lithium wire segments is added, with stirring, 21.3 gm (0.125 mole) of l-methyl-l,2,3,4-tetrahydroquinoline, and the mixture is stirred for 16J hr under a nitrogen atmosphere. The un reacted lithium is removed, the excess n-propylamine is distilled from the flask, the semisolid residue is cooled in an ice bath, overlaid with ether, and then neutralized slowly with solid ammonium chloride. The mixture is cautiously diluted with water, the ether layer separated, the water layer extracted with ether, the ether layers combined, dried, concentrated, and the residue is distilled to alford 19.8 gm... 

Vigorous chemical reduction (e.g. Sn-HCl or Zn-HCl) effects complete reduction of the heterocyclic ring, e.g. 1-methylquinolinium ion yields 1-methyl-1,2,3,4-tetrahydroquinoline. Reversible reduction of the pyridinium ring of coenzymes I and II (335 Y = H and P03H2, respectively) is important physiologically (B-97MI502-07). 

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